PEGylated liposomes are potential candidates to improve the pharmacokinetic characteristics of encapsulated drugs, to extend their circulation half-life and facilitate their passive accumulation at tumour sites. Howev...PEGylated liposomes are potential candidates to improve the pharmacokinetic characteristics of encapsulated drugs, to extend their circulation half-life and facilitate their passive accumulation at tumour sites. However, PEG-modified liposomes can induce accelerated blood clearance(ABC) upon repeated administration, and the extent of ABC phenomenon on the cytotoxic drugs-containing PEGylated liposomes is related to the dose of the cytotoxic drugs.In this study, EPI served as a model cytotoxic drug, a hydrophilic surfactant molecule,monosialylganglioside(GM1) was chosen and modified on the liposomes together with PEG.It was shown that upon mixed modification, when GM1 contents reached 10% or 15% mol,the ABC phenomenon of the PEGylated liposomal EPI significantly reduced. We also found that GM1 played an important role in abrogating the ABC phenomenon in both the induction phase and the effectuation phase. The results suggested that GM1 incorporation unfortunately did not avoid occurrence of ABC phenomenon completely, but GM1 modification on PEGylated liposomes may provide a significant improvement in clinical practice of PEGylated liposomes. Further study must be necessary.展开更多
BACKGROUND Pegylated liposomal doxorubicin(PLD)uses the hydrophilic layer of liposomes to reach the sweat on the skin surface or accumulate in the sweat glands,producing toxic free radicals and oxidative damage,result...BACKGROUND Pegylated liposomal doxorubicin(PLD)uses the hydrophilic layer of liposomes to reach the sweat on the skin surface or accumulate in the sweat glands,producing toxic free radicals and oxidative damage,resulting in hand-foot syndrome(HFS).Regional cooling can induce vasoconstriction to reduce the release of drugs in the limbs and reduce the accumulation of drugs in sweat glands;thus,decreasing the incidence and severity of HFS.AIM To study the efficacy of cooling patches to prevent HFS caused by PLD in the short-term.METHODS This is a retrospective cohort study.Female breast cancer patients(n=101)who were treated with PLD in two breast wards at our department from February 2020 to February 2021 were enrolled in the study and were randomly divided into the cooling group(51 patients)and the control group(50 patients).Patients in the control group only received routine care,while the patients in the cooling group applied cooling patches,based on routine care,to the palm and back of the hands 15 min before chemotherapy infusion for 10 h.All patients took a corresponding dose of dexamethasone orally one day before chemotherapy,on the day of chemotherapy,and one day after chemotherapy.SPSS23.0 version was used to analyze the data in this study.The occurrence and severity of HFS was analyzed by the Mann-Whitney U test,and scores were analyzed by the Student’s t test or Wilcoxon rank-sum test.A P value<0.05 was regarded as statistically significant.RESULTS In this study,neither group of patients developed Grade 3 HFS.In the control group,the incidence of Grade 1 HFS and Grade 2 HFS was 38%and 2%,respectively.However,in the cooling group,only one person developed Grade 1 HFS(2%),and none of the patients developed Grade 2 HFS.These findings showed that cooling patches can effectively reduce the frequency and severity of HFS(P<0.0001)in the short-term.Before the fourth chemotherapy cycle,although general self-efficacy scale scores in the cooling group were low,they were still significantly higher than those in the control group(17.22±5.16 vs 19.63±6.42,P=0.041).Compared with the control group,the mean Hand-Foot Skin Reaction and Quality of Life Questionnaire score in the cooling group was significantly lower(18.08±7.01 vs 14.20±7.39,P=0.008).CONCLUSION Cooling patches can effectively reduce the frequency and severity of HFS caused by PLD in the short-term.In addition,it may help delay the decline in patients’self-efficacy.展开更多
AIM: To improve the results of New therapeutic strategies in hepatocellular carcinoma (HCC). We have conducted a phase Ⅱ study with pegylated liposomal doxorubicin (PLD), 5-fluorouracil (5FU) and folinic acid (FA). M...AIM: To improve the results of New therapeutic strategies in hepatocellular carcinoma (HCC). We have conducted a phase Ⅱ study with pegylated liposomal doxorubicin (PLD), 5-fluorouracil (5FU) and folinic acid (FA). METHODS: Thirty-one patients with hystologically- confirmed, inoperable HCC, received combination chemotherapy with PLD 25 mg/mq on d 1, 5FU 1200 mg/mq in 48 h continuous infusion, and oral FA 30 mg on d 1 and 2 every 3 wk until disease progression or intolerable toxicity. RESULTS: The median age was 65 years (range 41-82) and 28 patients were hepatitis C virus seropositive (90%). The majority of patients were Child-Pugh Class B (55%). Two patients showed a partial response (PR), and 16 had stable disease (SD). With a median follow-up of 14 mo, the median time to progression of all evaluable patients was 4 mo (95% CI 1.7-7). Median overall survival was 9 mo (95% CI 3-24 mo). After 1 year, 9 of 18 PR/SD patients were alive. Chemotherapy was well tolerated. CONCLUSION: PLD/FU/FA combination seems capable of achieving durable stabilization of HCC. The manageable toxicity supports a role for combination with other anticancer agents.展开更多
AIM: To assess the efficacy and safety of the combination of pegylated liposomal doxorubicin(PLD) and carboplatin in patients with recurrent epithelial ovarian carcinoma(ROC), following disease progression on single a...AIM: To assess the efficacy and safety of the combination of pegylated liposomal doxorubicin(PLD) and carboplatin in patients with recurrent epithelial ovarian carcinoma(ROC), following disease progression on single agent PLD. METHODS: An analysis of the medical records of 10 patients with ROC, treated in our institution with a combination of PLD and carboplatin following progression on single-agent PLD therapy was performed. The median age was 59.1 years(range, 45 to 77 years). All diagnoses were histological-proven. Eight of the 10 patients were platinum-resistant. Following disease progression on single-agent PLD treatment, carboplatin area under the curve(AUC)-5 was added to PLD in all 10 patients. In order to assess disease status, Ca-125 was assessed before each PLD/carboplatin treatment. Relative changes in Ca-125 values were calculated, and response defined as a greater than 50% reduction in Ca-125 from baseline. Radiographic studies were reevaluated and responses to therapy based on com-puter tomography(CT) scans carried out on a regular basis every 2-3 mo in each patient. Statistical analysis was performed using SPSS(V19).RESULTS: A median of 10 cycles(range, 2-26) of the carboplatin-PLD combination was given. Of the 10 treated patients, 6 had > 50% reduction in Ca-125 levels from baseline, 4 of these had a partial response according to Response Evaluation Criteria in Solid Tumors(RECIST) criteria, and the other 2 patients had no measurable disease. In a further 2 patients with a best response of disease stabilization and < 50% reduction of Ca-125 levels, one had progression of disease after 26 cycles, and the second progressed with brain metastases following 12 cycles. Seven of the eight patients who were platinum-resistant showed evidence of clinical benefit on carboplatin-PLD combination therapy; 5 of these had > 50% reduction in Ca-125 level, 4 also showed a partial response on CT scan. The treatment was generally well-tolerated by the patients. CONCLUSION: Addition of carboplatin to PLD, after disease progression on single-agent PLD therapy, is both effective and safe in patients with ROC, even in those with Platinum-resistant disease.展开更多
Purpose:?The treatment of advanced breast cancer (ABC) is still challenging aiming mainly to improve or maintain the quality of life. The efficacy of pegylated liposomal doxorubicin (PLD) was proven in patients with A...Purpose:?The treatment of advanced breast cancer (ABC) is still challenging aiming mainly to improve or maintain the quality of life. The efficacy of pegylated liposomal doxorubicin (PLD) was proven in patients with ABC.?Because its expensive treatment?there is a great need to find the predictive factors for the clinical outcome of PLD.?Our purpose was to evaluate the factors which?would affect the clinical outcomes in patients receiving PLD for advanced breast cancer. Methods: Retrospectively, we studied the medical records of 60 eligible patients during the period of seven years (Jan.?2011-Dec.?2017).?All patients?were treated in Medical Oncology Department, South Egypt Cancer Institute, Assiut?University,?Egypt. We included only patients with visceral metastasis who received at least 2 cycles of PLD and had radiological assessment after that. Clinical benefit rate of PLD and survival outcome were assessed and correlated with patients and disease?characteristic. Results:?The majority of patients had a performance status grade II (81.7%), recurrent disease (86.7%), more than one metastatic site (83.3%), and chemoresistance to previous anthracycline (75%).?The clinical benefit rate (CBR) to PDL was 30%. We found statistical?significant association between higher CBR and biological subtypes (p??0.001), type of metastatic breast disease (p?=?0.003), chemosensitivity to anthracycline (p??0.001), and the number of previous lines of chemotherapy (p?=?0.041).?The median progression-free survival (PFS) was five months. There was a statistically-significant improvement of PFS among patients with anthracycline-sensitive tumors compared to those with anthracycline-resistant tumors (10 months vs. 5 months, respectively, p?=?0.004). The most common toxicity was palmar-plantar erythrodysesthesia (28% for all grade and 9% for grade 3 or more). There was no severe cardiotoxicity or treatment-related death.?Conclusion:?Pegylated liposomal doxorubicin appears to be more effective in patients?with (luminal B with Her2neu?positive, triple-negative and in her2neu amplified), also we noticed that de novo metastatic disease, patient who are not heavily pretreated tumors and patients with the anthracycline-sensitive tumor get more benefit from PLD than others.展开更多
<strong>Introduction:</strong> <span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">The treatment of meta...<strong>Introduction:</strong> <span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">The treatment of metastatic breast cancer (MBC) is still challenging.</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">Many studies documented the efficacy of</span></span></span><span><span><span style="font-family:""> </span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">pegylated liposomal doxorubicin (PLD) in patients with MBC, but there is a limited data about the cardiac safety with high cumulative dose (HCD) of PLD. </span><b><span style="font-family:Verdana;">Aim of the work:</span></b></span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">We conducted this trial to outline the cardiac safety of HCD of PLD in patients </span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">with MBC who previously received conventional anthracyclines. </span><b><span style="font-family:Verdana;">Methods:</span></b> <span style="font-family:Verdana;">During the period of nine years (January 2011 to December 2019). We extracted</span><span style="font-family:Verdana;"> the data of the patients with MBC receiving PLD at Medical Oncology Department, South Egypt Cancer Institute, Assiut University. These included patients’ demographics and therapeutic data including the full data of PLD, prior conventional anthracyclines, prior trastuzumab, and prior radiotherapy. Also, data about comorbidities as well as cardiac and other toxicities of PLD were obtained. The data was analysed using SPSS v. 21. </span><b><span style="font-family:Verdana;">Results:</span></b><span style="font-family:Verdana;"> For all 81 eligible patients, the mean age was 43.9 years (±standard deviation (SD) 13.2). The mean cumulative dose of PLD was 378.4 mg/m</span><sup><span style="font-family:Verdana;">2</span></sup><span style="font-family:Verdana;"> (± SD of 250.2) and a range of 100</span></span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">-</span></span></span><span><span><span style="font-family:""> </span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">1200 mg/m</span><sup><span style="font-family:Verdana;">2</span></sup><span style="font-family:Verdana;">. About thirty-one (38.3%) patients received high </span><span><span style="font-family:Verdana;">cumulative dose (400 mg/m</span><sup><span style="font-family:Verdana;">2</span></sup><span style="font-family:Verdana;"> or more), while the remaining 50 patients did not.</span></span></span></span></span><span><span><span style="font-family:""> </span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">The decline in </span><a name="_Hlk36276945"></a><span style="font-family:Verdana;">left ventricular ejection fraction (LVEF) was relatively rare;and</span></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> of low grade. Grade 2 decline in LVEF occurred in only two patients who received high cumulative dose of PLD, and only one patient who did not reach HCD (p</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">= </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">0</span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">.555). Grade 3 or 4 decline in LVEF did not occur in patients either with or without HCD. Regarding other toxicities, there was a significant increase in incidence of all grades palmar plantar erythrodysesthesia (PPE) in </span><span style="font-family:Verdana;">patients </span></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">who </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">received HCD of PLD when compared to those </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">who </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">did not reach</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> the HCD (38.7% versus 16% respectively;p</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">=</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> 0</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">.021).</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><b><span style="font-family:Verdana;">Conclusion: </span></b></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">Our </span><span style="font-family:Verdana;">study concluded that the use of PLD seems to be a justified agent in the treatment</span><span style="font-family:Verdana;"> of MBC who previously treated by</span></span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">conventional anthracyclines in the adjuvant, metastatic or both settings, even in patients reaching the cumulative dose of conventional anthracycline.</span></span></span>展开更多
OBJECTIVE Though doxorubicin is highly activein the treatment of multiple myeloma, its toxicityprofile limits its therapeutic index. We performed thisstudy to evaluate the efficacy and safety of pegylatedliposomal dox...OBJECTIVE Though doxorubicin is highly activein the treatment of multiple myeloma, its toxicityprofile limits its therapeutic index. We performed thisstudy to evaluate the efficacy and safety of pegylatedliposomal doxorubicin (PLD, Caelyx^(?)), vincristine,and reduced-dose dexamethasone combinationtherapy in newly diagnosed multiple myeloma (MM)patients in a Chinese population.METHODS This was an open-label, single-armstudy in which newly diagnosed patients with MMreceived PLD 40 mg/m^2 intravenously on Day 1,vincristine 1.4 mg/m^2 intravenously (maximum 2 mg)on Day 1, and 40 mg of dexarnethasone (intravenouslyor orally) from Day 1 to Day 4. Treatment wasrepeated every 28 days for at least 4 cycles.RESULTS In the intent-to-treat (ITT) analysis, theoverall response rate was 68.29%, and the completeremission rate was 10.98%. The incidence of alladverse events was 46.34%. The most commonnon-hematologic toxicities were palmar-plantarerythrodysesthesia (13.4%) and stomatitis (6.1%).CONCLUSION PLD, vincristine, and a reduceddosedexamethasone combination (DVd) is aneffective and safe regimen in newly diagnosed MMpatients in a Chinese population.展开更多
OBJECTIVE Pegylated liposomal doxorubicin (PLD;CAELYX^(?)), a novel formulation of doxorubicin with enhancedtherapeutic efficacy and reduced toxicity, has demonstratedimproved progression-free survival in recurrent or...OBJECTIVE Pegylated liposomal doxorubicin (PLD;CAELYX^(?)), a novel formulation of doxorubicin with enhancedtherapeutic efficacy and reduced toxicity, has demonstratedimproved progression-free survival in recurrent or refractoryovarian cancer. The objective of this open-label, noncomparative,observational study was to determine the efficacyand safety of PLD monotherapy or combination therapy withcarboplatin for patients with recurrent or refractory ovariancancer.METHODS Sixty-two patients with recurrent or refractoryovarian cancer who completed a platinum-based chemotherapyregimen and demonstrated platinum sensitivity for first-linetreatment at least 6 months prior to study entry were enrolledin 20 centers in China. PLD was given as monotherapy (50mg/m^2 infused over 60 minutes) or as combination therapy(30 mg/m^2 1-hour infusion) with carboplatin (area under thecurve 5 mg.min/mL 1-hour infusion) on day 1 every 28 daysfor 4 cycles. The primary endpoint was objective response (OR)rate or CA-125 level. Secondary endpoints included time toresponse, time-to-progression, health-related quality of life, andsafety.RESULTS Overall, 48% of the 62 evaluable patients achieveda confirmed OR. More patients receiving PLD and carboplatinachieved an OR vs the PLD monotherapy group (63% vs. 37%).The median time to response and disease progression was58.5 days and 56.0 days, respectively. Overall and drug-relatedadverse events were reported for 39% and 34%, respectively.The most commonly reported adverse events were stomatitis(22.6%) and palmar-plantar erythroderma (9.7%). Two deathswere reported.CONCLUSION PLD is an effective and well tolerated agentin women with recurrent or refractory epithelial ovarian cancer.展开更多
OBJECTIVE To evaluate the efficacy and adverse effects ofgemcitabine versus pegylated liposomal doxorubicin in patientswith progressive or recurrent ovarian cancer.METHODS We conducted a systematic literature search t...OBJECTIVE To evaluate the efficacy and adverse effects ofgemcitabine versus pegylated liposomal doxorubicin in patientswith progressive or recurrent ovarian cancer.METHODS We conducted a systematic literature search toidentify all randomized controlled trials comparing gemcitabineand pegylated liposomal doxorubicin for progressive orrecurrent ovarian cancer. Trial data were reviewed and extractedindependently by 2 reviewers. We evaluated the quality of theincluded studies using the Handbook 5.0 recommend standardsand then analyzed data by Cochrane Collaboration's RevMan 5.0.RESULTS Two trials which included a total of 348 patients wereanalyzed. The results of meta-analysis showed that gemcitabineimproved disease control rates significantly better than pegylatedliposomal doxorubicin. A greater number of patients receivinggemcitabine experienced neutropenia compared with patientsreceiving pegylated liposomal doxorubicin; however, hand-footsyndrome and mucositis were more severe in patients receivingpegylated liposomal doxorubicin.CONCLUSION Gemcitabine provided a limited advantagecompared with pegylated liposomal doxorubicin. There existsan urgent need for more high-quality, multicenter, adequaterandomized, controlled clinical trials for comparing gemcitabinewith pegylated liposomal doxorubicin in patients withprogressive/recurrent ovarian cancer.展开更多
OBJECTIVE To determine the characterization,anti-tumor efficacy and pharmacokinetics of bufalin-loaded PEGylated liposomes compared with bufalin entity.METHODS Bufalin-loaded PEGylated liposomes and bufalin-loaded lip...OBJECTIVE To determine the characterization,anti-tumor efficacy and pharmacokinetics of bufalin-loaded PEGylated liposomes compared with bufalin entity.METHODS Bufalin-loaded PEGylated liposomes and bufalin-loaded liposomes were prepared reproducibly with homogeneous particle size by the combination of thin film evaporation method and high pressure homogenization method.The particle size and zeta potential of the liposomes were determined by dynamic light scattering technique.The direct imaging of morphology of liposomes was charactered by transmission electron microscope.The content of bufalin in liposomes was analysed by HPLC method.The entrapment efficiency and the particle size was applied to assess the stability profile,after storage at 4℃ on day 0,7,15,30 and 90.The in-vitro release behaviours of bufalin from liposomes were conducted using dialysis bag technique at 37℃.In-vitro cytotoxicity studies were carried out using MTT[3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide]assay on several kinds of tumor cel lines including SW620,PC-3,MDA-MB-231,A549,U251,U87 and HepG2.In-vivo pharmacokinetic study of bufalin liposomes was evaluated by HPLC method.RESULTS Their mean particle sizes were 127.6 nm and 155.0 nm,mean zeta potentials were 2.24 m V and-18.5 m V,entrapment efficiencies were 76.31%and 78.40%,respectively.In-vitro release profile revealed that the release of bufalin in bufalin-loaded PEGylated liposomes was slower than that of bufalin-loaded liposomes.The cytotoxicity of blank liposomes has been found within acceptable range,whereas bufalin-loaded PEGylated liposomes showed enhanced cytotoxicity to U251 cells compared with bufalin entity.In-vivo pharmacokinetics indicated that bufalinloaded PEGylated liposomes could extend eliminate half-life time of bufalin in plasma in rats.CONCLUSION The results suggested that bufalin-loaded PEGylated liposomes improved the solubility and increased the drug concentration in plasma.展开更多
Objective:This study aimed to develop a new polyethylene glycol(PEG)ylatedβ-elemene liposome(PEG-Lipo-β-E)and evaluate its characterization,pharmacokinetics,antitumor effects and safety in vitro and in vivo.Methods:...Objective:This study aimed to develop a new polyethylene glycol(PEG)ylatedβ-elemene liposome(PEG-Lipo-β-E)and evaluate its characterization,pharmacokinetics,antitumor effects and safety in vitro and in vivo.Methods:The liposomes were prepared by ethanol injection and high-pressure micro-jet homogenization.Characterization of the liposomes was conducted,and drug content,entrapment efficiency(EE),in vitro release and stability were studied by ultra-fast liquid chromatography(UFLC)and a liquid surface method.Blood was drawn from rats to establish the pharmacokinetic parameters.The anticancer effect was evaluated in a KU-19-19 bladder cancer xenograft model.Histological analyses were performed to evaluate safety.Results:The PEG-Lipo-β-E showed good stability and was characterized as 83.31±0.181 nm in size,0.279±0.004 in polydispersity index(PDI),-21.4±1.06 mV in zeta potential,6.65±0.02 in pH,5.024±0.107 mg/mL inβ-elemene(β-E)content,and 95.53±1.712%in average EE.The Fourier transform infrared spectroscopy(FTIR)and differential scanning calorimetry(DSC)indicated the formation of PEG-Lipo-β-E.Compared to elemene injection,PEG-Lipo-β-E demonstrated a 1.75-fold decrease in clearance,a 1.62-fold increase in half-life,and a 1.76-fold increase in area under the concentration-time curves(AUCs)from 0 hour to 1.5 hours(P<0.05).PEG-Lipo-β-E also showed an enhanced anticancer effect in vivo.Histological analyses showed that there was no evidence of toxicity to the heart,kidney,liver,lung or spleen.Conclusions:The present study demonstrates PEG-Lipo-β-E as a new formulation with ease of preparation,high EE,good stability,improved bioavailability and antitumor effects.展开更多
This study aimed to investigate the ability of the novel materials D-α-tocopheryl poly(2-ethyl-2-oxazoline) succinate(TPOS) to construct pH-sensitive liposomes. TPOS was initially synthesized and characterized by TLC...This study aimed to investigate the ability of the novel materials D-α-tocopheryl poly(2-ethyl-2-oxazoline) succinate(TPOS) to construct pH-sensitive liposomes. TPOS was initially synthesized and characterized by TLC, FTIR, and ~1H-NMR. The buffering capacity of polyethylene glycol-distearoyl phosphatidylethanolamine(PEG-DSPE) and TPOS was determined by acid-base titration, and TPOS displayed a slower downtrend and gentler slope of titration curve than PEG-DSPE within pH 7.4–5.0. Studies on the in vitro drug release demonstrated that TPOS modified docetaxel(DOC) liposomes(TPOS-DOC-L) had a slower drugrelease rate at pH 7.4 similar to PEGylated-DOC liposomes(PEG-DOC-L), whereas the release rate reached approximately 86.92% ± 1.69% at pH 6.4. In vitro cellular uptake assays by microplate reader, and flow cytometry revealed that TPOS modified coumarin 6 liposomes(TPOS-C6-L) had stronger cellular uptake at pH 6.4 than that at pH 7.4( P < 0.01). Conversely, for PEGylated C6 liposomes(PEG-C6-L) and conventional C6 liposomes(C6-L), very similar cellular uptakes were exhibited at different pH values. Confocal laser scanning microscopy images showed that PEG-C6-L and C6-L were mainly located in lysosomes. By contrast, TPOS-C6-L showed broader cytoplasmic release and distribution at 4 h. MTT assay showed that the cytotoxicity of TPOS-DOC-L was similar to that of PEG-DOC-L and conventional DOC liposomes(DOC-L) at the same DOC concentration and at pH 7.4, but was much lower than those at pH 6.4 after 48 h of incubation. The apoptosis of PEG-DOC-L and DOC-L had no remarkable improvement with decreased pH from 7.4 to 6.4. Meanwhile, TPOS-DOC-Lsignificantly induced the apoptosis of HeLa cells with decreased pH. Therefore, TPOS can be a biomaterial for the construction of a pH-sensitive drug delivery system.展开更多
There is now little doubt that PEGylation is useful and is in widespread use because it provides a prolonged half-life,a higher stability and a lowerimmunogenicity[1].However,it is of concern that PEGylation may affec...There is now little doubt that PEGylation is useful and is in widespread use because it provides a prolonged half-life,a higher stability and a lowerimmunogenicity[1].However,it is of concern that PEGylation may affect the physicochemical and pharmacokinetic characteristics of protein-encapsulated liposome.Thus,we prepared the bovine serum albumin(BSA)-encapsulated liposome(BSA-liposome)with or without PEG and then compared their physicochemical and pharmacokinetic characteristics(Fig.1).BSA-liposomes were prepared by the thin-film hydration method.展开更多
For systemic injection of cationic liposome/plasmid DNA (pDNA) complexes (cationic lipoplexes), polyethylene glycol (PEG)-modification (PEGylation) of lipoplexes can enhance their systemic stability. In this study, we...For systemic injection of cationic liposome/plasmid DNA (pDNA) complexes (cationic lipoplexes), polyethylene glycol (PEG)-modification (PEGylation) of lipoplexes can enhance their systemic stability. In this study, we examined whether intravenous injection of PEGylated cationic lipoplexes into tumor-bearing mice could deliver pDNA into tumor tissues and induce transgene expression. PEGylation of cationic liposomes could prevent their agglutination with erythrocytes. However, when PEGylated cationic lipoplexes were injected intravenously into tumor-bearing mice, they accumulated in tumor vascular vessels and did not exhibit transgene expression in tumors with both poor and well-developed vascularization. Furthermore, PEGylated cationic lipoplexes of CpG- free pDNA could not increase transgene expression in tumors after intravenous injection. These results suggested that PEGylation could not extravasate cationic lipoplexes from vascular vessels in tumors and abolished transgene expression although it enhanced the systemic stability of cationic lipoplexes by avoiding interactions with blood components such as erythrocytes. Successful delivery of pDNA to tumors by PEGylated cationic liposomes will require a rational strategy and the design of liposomal delivery systems to overcome the issue associated with the use of PEG.展开更多
OBJECTIVE: To investigate whether the Tandistribution and anti-tumor Ⅱef A could improve the ficacy of Pegylated Liposomal Doxorubicin(PLD) via normalizing the structure and function of vasculature in Hepa1-6 hepatom...OBJECTIVE: To investigate whether the Tandistribution and anti-tumor Ⅱef A could improve the ficacy of Pegylated Liposomal Doxorubicin(PLD) via normalizing the structure and function of vasculature in Hepa1-6 hepatoma mice model.METHODS: Hepa1-6 hepatoma-bearing mice were treated with TanⅡA for 14 d. Distribution and anti-tumor efficacy of PLD, and the structure and function of the tumor vasculature were evaluated using various techniques.RESULTS: TanⅡ A significantly reduced the micro-vessel density(MVD). After Tan vascular walls were betteⅡr s A treatment,the tumor tructured, as the increased coverage of the pericytes and the promoted contact of the basement membrane and endothelial cell. Functional tests showed that tumor hypoxia was improved and the exudation amount of Evans blue in the parenchyma of the tumor decreased. In addition, mice treated with TanA had greater PLD penetration distance intratumoⅡrally. Furthermore, combined therapy of Tanibited tumor growth.ⅡA and PLD significantly inhCONCLUSION: This study suggests that Tanasculature andⅡ h A helps normalizing the tumor vas therapeutic potential in increasing the distribution of chemotherapy drug in the tumor.展开更多
Alzheimer’s disease is a neurodegenerative condition leading to atrophy of the brain and robbing nearly 5.8 million individuals in the United States age 65 and older of their cognitive functions.Alzheimer’s disease ...Alzheimer’s disease is a neurodegenerative condition leading to atrophy of the brain and robbing nearly 5.8 million individuals in the United States age 65 and older of their cognitive functions.Alzheimer’s disease is associated with dementia and a progressive decline in memory,thinking,and social skills,eventually leading to a point that the individual can no longer perform daily activities independently.Currently available drugs on the market temporarily alleviate the symptoms,however,they are not successful in slowing down the progression of Alzheimer’s disease.Treatment and cures have been constricted due to the difficulty of drug delivery to the blood-brain barrier.Several studies have led to identification of vesicles to transport the necessary drugs through the blood-brain barrier that would typically not achieve the targeted area through systemic delivered medications.Recently,liposomes have emerged as a viable drug delivery agent to transport drugs that are not able to cross the blood-brain barrier.Liposomes are being used as a component of nanoparticle drug delivery;due to their biocompatible nature;and possessing the capability to carry both lipophilic and hydrophilic therapeutic agents across the blood brain barrier into the brain cells.Studies indicate the importance of liposomal based drug delivery in treatment of neurodegenerative disorders.The idea is to encapsulate the drugs inside the properly engineered liposome to generate a response of treatment.Liposomes are engineered to target specific diseased moieties and also several surface modifications of liposomes are under research to create a clinical path to the management of Alzheimer’s disease.This review deals with Alzheimer’s disease and emphasize on challenges associated with drug delivery to the brain,and how liposomal drug delivery can play an important role as a drug delivery method for the treatment of Alzheimer’s disease.This review also sheds some light on variation of liposomes.Additionally,it emphasizes on the liposomal formulations which are currently researched or used for treatment of Alzheimer’s disease and also discusses the future prospect of liposomal based drug delivery in Alzheimer’s disease.展开更多
Purpose: To explore the preventive effect of Regional cooling comprehensive nursing on hand foot syndrome caused by pegylated liposomal doxorubicin (PLD). Method: Adopt overall sampling method. Patients who used the s...Purpose: To explore the preventive effect of Regional cooling comprehensive nursing on hand foot syndrome caused by pegylated liposomal doxorubicin (PLD). Method: Adopt overall sampling method. Patients who used the same adjuvant drugs from January to December 2020 were randomly divided into an intervention group and a control group. The patients in the two groups received routine nursing guidance and drug prevention for the use of amygdalin. The patients in the intervention group were required to take protective measures of Regional cooling during chemotherapy. The occurrence of hand foot syndrome during adriamycin liposome administration was compared between the two groups. Results: By comparing the adverse reactions of cases during Adriamycin Administration, the incidence rates of grade I, II and III hand foot syndrome in the control group were 28.8%, 7.6% and 27.5% respectively, and the incidence rates of grade I, II and III hand foot syndrome in the intervention group were 42.1%, 12.3% and 7.0% respectively, with statistical significance (P Conclusion: Regional cooling nursing and preventive behavior guidance can effectively reduce the severity of hand foot syndrome caused by adriamycin.展开更多
基金supported by the National Natural Science Foundation of China (Grant No.81373334)
文摘PEGylated liposomes are potential candidates to improve the pharmacokinetic characteristics of encapsulated drugs, to extend their circulation half-life and facilitate their passive accumulation at tumour sites. However, PEG-modified liposomes can induce accelerated blood clearance(ABC) upon repeated administration, and the extent of ABC phenomenon on the cytotoxic drugs-containing PEGylated liposomes is related to the dose of the cytotoxic drugs.In this study, EPI served as a model cytotoxic drug, a hydrophilic surfactant molecule,monosialylganglioside(GM1) was chosen and modified on the liposomes together with PEG.It was shown that upon mixed modification, when GM1 contents reached 10% or 15% mol,the ABC phenomenon of the PEGylated liposomal EPI significantly reduced. We also found that GM1 played an important role in abrogating the ABC phenomenon in both the induction phase and the effectuation phase. The results suggested that GM1 incorporation unfortunately did not avoid occurrence of ABC phenomenon completely, but GM1 modification on PEGylated liposomes may provide a significant improvement in clinical practice of PEGylated liposomes. Further study must be necessary.
文摘BACKGROUND Pegylated liposomal doxorubicin(PLD)uses the hydrophilic layer of liposomes to reach the sweat on the skin surface or accumulate in the sweat glands,producing toxic free radicals and oxidative damage,resulting in hand-foot syndrome(HFS).Regional cooling can induce vasoconstriction to reduce the release of drugs in the limbs and reduce the accumulation of drugs in sweat glands;thus,decreasing the incidence and severity of HFS.AIM To study the efficacy of cooling patches to prevent HFS caused by PLD in the short-term.METHODS This is a retrospective cohort study.Female breast cancer patients(n=101)who were treated with PLD in two breast wards at our department from February 2020 to February 2021 were enrolled in the study and were randomly divided into the cooling group(51 patients)and the control group(50 patients).Patients in the control group only received routine care,while the patients in the cooling group applied cooling patches,based on routine care,to the palm and back of the hands 15 min before chemotherapy infusion for 10 h.All patients took a corresponding dose of dexamethasone orally one day before chemotherapy,on the day of chemotherapy,and one day after chemotherapy.SPSS23.0 version was used to analyze the data in this study.The occurrence and severity of HFS was analyzed by the Mann-Whitney U test,and scores were analyzed by the Student’s t test or Wilcoxon rank-sum test.A P value<0.05 was regarded as statistically significant.RESULTS In this study,neither group of patients developed Grade 3 HFS.In the control group,the incidence of Grade 1 HFS and Grade 2 HFS was 38%and 2%,respectively.However,in the cooling group,only one person developed Grade 1 HFS(2%),and none of the patients developed Grade 2 HFS.These findings showed that cooling patches can effectively reduce the frequency and severity of HFS(P<0.0001)in the short-term.Before the fourth chemotherapy cycle,although general self-efficacy scale scores in the cooling group were low,they were still significantly higher than those in the control group(17.22±5.16 vs 19.63±6.42,P=0.041).Compared with the control group,the mean Hand-Foot Skin Reaction and Quality of Life Questionnaire score in the cooling group was significantly lower(18.08±7.01 vs 14.20±7.39,P=0.008).CONCLUSION Cooling patches can effectively reduce the frequency and severity of HFS caused by PLD in the short-term.In addition,it may help delay the decline in patients’self-efficacy.
文摘AIM: To improve the results of New therapeutic strategies in hepatocellular carcinoma (HCC). We have conducted a phase Ⅱ study with pegylated liposomal doxorubicin (PLD), 5-fluorouracil (5FU) and folinic acid (FA). METHODS: Thirty-one patients with hystologically- confirmed, inoperable HCC, received combination chemotherapy with PLD 25 mg/mq on d 1, 5FU 1200 mg/mq in 48 h continuous infusion, and oral FA 30 mg on d 1 and 2 every 3 wk until disease progression or intolerable toxicity. RESULTS: The median age was 65 years (range 41-82) and 28 patients were hepatitis C virus seropositive (90%). The majority of patients were Child-Pugh Class B (55%). Two patients showed a partial response (PR), and 16 had stable disease (SD). With a median follow-up of 14 mo, the median time to progression of all evaluable patients was 4 mo (95% CI 1.7-7). Median overall survival was 9 mo (95% CI 3-24 mo). After 1 year, 9 of 18 PR/SD patients were alive. Chemotherapy was well tolerated. CONCLUSION: PLD/FU/FA combination seems capable of achieving durable stabilization of HCC. The manageable toxicity supports a role for combination with other anticancer agents.
文摘AIM: To assess the efficacy and safety of the combination of pegylated liposomal doxorubicin(PLD) and carboplatin in patients with recurrent epithelial ovarian carcinoma(ROC), following disease progression on single agent PLD. METHODS: An analysis of the medical records of 10 patients with ROC, treated in our institution with a combination of PLD and carboplatin following progression on single-agent PLD therapy was performed. The median age was 59.1 years(range, 45 to 77 years). All diagnoses were histological-proven. Eight of the 10 patients were platinum-resistant. Following disease progression on single-agent PLD treatment, carboplatin area under the curve(AUC)-5 was added to PLD in all 10 patients. In order to assess disease status, Ca-125 was assessed before each PLD/carboplatin treatment. Relative changes in Ca-125 values were calculated, and response defined as a greater than 50% reduction in Ca-125 from baseline. Radiographic studies were reevaluated and responses to therapy based on com-puter tomography(CT) scans carried out on a regular basis every 2-3 mo in each patient. Statistical analysis was performed using SPSS(V19).RESULTS: A median of 10 cycles(range, 2-26) of the carboplatin-PLD combination was given. Of the 10 treated patients, 6 had > 50% reduction in Ca-125 levels from baseline, 4 of these had a partial response according to Response Evaluation Criteria in Solid Tumors(RECIST) criteria, and the other 2 patients had no measurable disease. In a further 2 patients with a best response of disease stabilization and < 50% reduction of Ca-125 levels, one had progression of disease after 26 cycles, and the second progressed with brain metastases following 12 cycles. Seven of the eight patients who were platinum-resistant showed evidence of clinical benefit on carboplatin-PLD combination therapy; 5 of these had > 50% reduction in Ca-125 level, 4 also showed a partial response on CT scan. The treatment was generally well-tolerated by the patients. CONCLUSION: Addition of carboplatin to PLD, after disease progression on single-agent PLD therapy, is both effective and safe in patients with ROC, even in those with Platinum-resistant disease.
文摘Purpose:?The treatment of advanced breast cancer (ABC) is still challenging aiming mainly to improve or maintain the quality of life. The efficacy of pegylated liposomal doxorubicin (PLD) was proven in patients with ABC.?Because its expensive treatment?there is a great need to find the predictive factors for the clinical outcome of PLD.?Our purpose was to evaluate the factors which?would affect the clinical outcomes in patients receiving PLD for advanced breast cancer. Methods: Retrospectively, we studied the medical records of 60 eligible patients during the period of seven years (Jan.?2011-Dec.?2017).?All patients?were treated in Medical Oncology Department, South Egypt Cancer Institute, Assiut?University,?Egypt. We included only patients with visceral metastasis who received at least 2 cycles of PLD and had radiological assessment after that. Clinical benefit rate of PLD and survival outcome were assessed and correlated with patients and disease?characteristic. Results:?The majority of patients had a performance status grade II (81.7%), recurrent disease (86.7%), more than one metastatic site (83.3%), and chemoresistance to previous anthracycline (75%).?The clinical benefit rate (CBR) to PDL was 30%. We found statistical?significant association between higher CBR and biological subtypes (p??0.001), type of metastatic breast disease (p?=?0.003), chemosensitivity to anthracycline (p??0.001), and the number of previous lines of chemotherapy (p?=?0.041).?The median progression-free survival (PFS) was five months. There was a statistically-significant improvement of PFS among patients with anthracycline-sensitive tumors compared to those with anthracycline-resistant tumors (10 months vs. 5 months, respectively, p?=?0.004). The most common toxicity was palmar-plantar erythrodysesthesia (28% for all grade and 9% for grade 3 or more). There was no severe cardiotoxicity or treatment-related death.?Conclusion:?Pegylated liposomal doxorubicin appears to be more effective in patients?with (luminal B with Her2neu?positive, triple-negative and in her2neu amplified), also we noticed that de novo metastatic disease, patient who are not heavily pretreated tumors and patients with the anthracycline-sensitive tumor get more benefit from PLD than others.
文摘<strong>Introduction:</strong> <span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">The treatment of metastatic breast cancer (MBC) is still challenging.</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">Many studies documented the efficacy of</span></span></span><span><span><span style="font-family:""> </span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">pegylated liposomal doxorubicin (PLD) in patients with MBC, but there is a limited data about the cardiac safety with high cumulative dose (HCD) of PLD. </span><b><span style="font-family:Verdana;">Aim of the work:</span></b></span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">We conducted this trial to outline the cardiac safety of HCD of PLD in patients </span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">with MBC who previously received conventional anthracyclines. </span><b><span style="font-family:Verdana;">Methods:</span></b> <span style="font-family:Verdana;">During the period of nine years (January 2011 to December 2019). We extracted</span><span style="font-family:Verdana;"> the data of the patients with MBC receiving PLD at Medical Oncology Department, South Egypt Cancer Institute, Assiut University. These included patients’ demographics and therapeutic data including the full data of PLD, prior conventional anthracyclines, prior trastuzumab, and prior radiotherapy. Also, data about comorbidities as well as cardiac and other toxicities of PLD were obtained. The data was analysed using SPSS v. 21. </span><b><span style="font-family:Verdana;">Results:</span></b><span style="font-family:Verdana;"> For all 81 eligible patients, the mean age was 43.9 years (±standard deviation (SD) 13.2). The mean cumulative dose of PLD was 378.4 mg/m</span><sup><span style="font-family:Verdana;">2</span></sup><span style="font-family:Verdana;"> (± SD of 250.2) and a range of 100</span></span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">-</span></span></span><span><span><span style="font-family:""> </span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">1200 mg/m</span><sup><span style="font-family:Verdana;">2</span></sup><span style="font-family:Verdana;">. About thirty-one (38.3%) patients received high </span><span><span style="font-family:Verdana;">cumulative dose (400 mg/m</span><sup><span style="font-family:Verdana;">2</span></sup><span style="font-family:Verdana;"> or more), while the remaining 50 patients did not.</span></span></span></span></span><span><span><span style="font-family:""> </span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">The decline in </span><a name="_Hlk36276945"></a><span style="font-family:Verdana;">left ventricular ejection fraction (LVEF) was relatively rare;and</span></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> of low grade. Grade 2 decline in LVEF occurred in only two patients who received high cumulative dose of PLD, and only one patient who did not reach HCD (p</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">= </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">0</span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">.555). Grade 3 or 4 decline in LVEF did not occur in patients either with or without HCD. Regarding other toxicities, there was a significant increase in incidence of all grades palmar plantar erythrodysesthesia (PPE) in </span><span style="font-family:Verdana;">patients </span></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">who </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">received HCD of PLD when compared to those </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">who </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">did not reach</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> the HCD (38.7% versus 16% respectively;p</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">=</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> 0</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">.021).</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><b><span style="font-family:Verdana;">Conclusion: </span></b></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">Our </span><span style="font-family:Verdana;">study concluded that the use of PLD seems to be a justified agent in the treatment</span><span style="font-family:Verdana;"> of MBC who previously treated by</span></span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">conventional anthracyclines in the adjuvant, metastatic or both settings, even in patients reaching the cumulative dose of conventional anthracycline.</span></span></span>
文摘OBJECTIVE Though doxorubicin is highly activein the treatment of multiple myeloma, its toxicityprofile limits its therapeutic index. We performed thisstudy to evaluate the efficacy and safety of pegylatedliposomal doxorubicin (PLD, Caelyx^(?)), vincristine,and reduced-dose dexamethasone combinationtherapy in newly diagnosed multiple myeloma (MM)patients in a Chinese population.METHODS This was an open-label, single-armstudy in which newly diagnosed patients with MMreceived PLD 40 mg/m^2 intravenously on Day 1,vincristine 1.4 mg/m^2 intravenously (maximum 2 mg)on Day 1, and 40 mg of dexarnethasone (intravenouslyor orally) from Day 1 to Day 4. Treatment wasrepeated every 28 days for at least 4 cycles.RESULTS In the intent-to-treat (ITT) analysis, theoverall response rate was 68.29%, and the completeremission rate was 10.98%. The incidence of alladverse events was 46.34%. The most commonnon-hematologic toxicities were palmar-plantarerythrodysesthesia (13.4%) and stomatitis (6.1%).CONCLUSION PLD, vincristine, and a reduceddosedexamethasone combination (DVd) is aneffective and safe regimen in newly diagnosed MMpatients in a Chinese population.
文摘OBJECTIVE Pegylated liposomal doxorubicin (PLD;CAELYX^(?)), a novel formulation of doxorubicin with enhancedtherapeutic efficacy and reduced toxicity, has demonstratedimproved progression-free survival in recurrent or refractoryovarian cancer. The objective of this open-label, noncomparative,observational study was to determine the efficacyand safety of PLD monotherapy or combination therapy withcarboplatin for patients with recurrent or refractory ovariancancer.METHODS Sixty-two patients with recurrent or refractoryovarian cancer who completed a platinum-based chemotherapyregimen and demonstrated platinum sensitivity for first-linetreatment at least 6 months prior to study entry were enrolledin 20 centers in China. PLD was given as monotherapy (50mg/m^2 infused over 60 minutes) or as combination therapy(30 mg/m^2 1-hour infusion) with carboplatin (area under thecurve 5 mg.min/mL 1-hour infusion) on day 1 every 28 daysfor 4 cycles. The primary endpoint was objective response (OR)rate or CA-125 level. Secondary endpoints included time toresponse, time-to-progression, health-related quality of life, andsafety.RESULTS Overall, 48% of the 62 evaluable patients achieveda confirmed OR. More patients receiving PLD and carboplatinachieved an OR vs the PLD monotherapy group (63% vs. 37%).The median time to response and disease progression was58.5 days and 56.0 days, respectively. Overall and drug-relatedadverse events were reported for 39% and 34%, respectively.The most commonly reported adverse events were stomatitis(22.6%) and palmar-plantar erythroderma (9.7%). Two deathswere reported.CONCLUSION PLD is an effective and well tolerated agentin women with recurrent or refractory epithelial ovarian cancer.
文摘OBJECTIVE To evaluate the efficacy and adverse effects ofgemcitabine versus pegylated liposomal doxorubicin in patientswith progressive or recurrent ovarian cancer.METHODS We conducted a systematic literature search toidentify all randomized controlled trials comparing gemcitabineand pegylated liposomal doxorubicin for progressive orrecurrent ovarian cancer. Trial data were reviewed and extractedindependently by 2 reviewers. We evaluated the quality of theincluded studies using the Handbook 5.0 recommend standardsand then analyzed data by Cochrane Collaboration's RevMan 5.0.RESULTS Two trials which included a total of 348 patients wereanalyzed. The results of meta-analysis showed that gemcitabineimproved disease control rates significantly better than pegylatedliposomal doxorubicin. A greater number of patients receivinggemcitabine experienced neutropenia compared with patientsreceiving pegylated liposomal doxorubicin; however, hand-footsyndrome and mucositis were more severe in patients receivingpegylated liposomal doxorubicin.CONCLUSION Gemcitabine provided a limited advantagecompared with pegylated liposomal doxorubicin. There existsan urgent need for more high-quality, multicenter, adequaterandomized, controlled clinical trials for comparing gemcitabinewith pegylated liposomal doxorubicin in patients withprogressive/recurrent ovarian cancer.
基金Supported by Overall Innovation Plan Projects of Science and Technology of Shaanxi Province in China(2015KTZDSF02-01-02)
文摘OBJECTIVE To determine the characterization,anti-tumor efficacy and pharmacokinetics of bufalin-loaded PEGylated liposomes compared with bufalin entity.METHODS Bufalin-loaded PEGylated liposomes and bufalin-loaded liposomes were prepared reproducibly with homogeneous particle size by the combination of thin film evaporation method and high pressure homogenization method.The particle size and zeta potential of the liposomes were determined by dynamic light scattering technique.The direct imaging of morphology of liposomes was charactered by transmission electron microscope.The content of bufalin in liposomes was analysed by HPLC method.The entrapment efficiency and the particle size was applied to assess the stability profile,after storage at 4℃ on day 0,7,15,30 and 90.The in-vitro release behaviours of bufalin from liposomes were conducted using dialysis bag technique at 37℃.In-vitro cytotoxicity studies were carried out using MTT[3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide]assay on several kinds of tumor cel lines including SW620,PC-3,MDA-MB-231,A549,U251,U87 and HepG2.In-vivo pharmacokinetic study of bufalin liposomes was evaluated by HPLC method.RESULTS Their mean particle sizes were 127.6 nm and 155.0 nm,mean zeta potentials were 2.24 m V and-18.5 m V,entrapment efficiencies were 76.31%and 78.40%,respectively.In-vitro release profile revealed that the release of bufalin in bufalin-loaded PEGylated liposomes was slower than that of bufalin-loaded liposomes.The cytotoxicity of blank liposomes has been found within acceptable range,whereas bufalin-loaded PEGylated liposomes showed enhanced cytotoxicity to U251 cells compared with bufalin entity.In-vivo pharmacokinetics indicated that bufalinloaded PEGylated liposomes could extend eliminate half-life time of bufalin in plasma in rats.CONCLUSION The results suggested that bufalin-loaded PEGylated liposomes improved the solubility and increased the drug concentration in plasma.
基金supported by grants from National Natural Science Foundation of China(Grant No.81672932,81874380 and 81730108)Zhejiang Provincial Natural Science Foundation of China for Distinguished Young Scholars(Grant No.LR18H160001)+7 种基金Zhejiang Provincial Natural Science Foundation of China(Grant No.LY15H160028 and LY13H130002)the Science and Technology Development Fund,Macao SAR(130/2017/A3,0099/2018/A3)Zhejiang Province Medical Science and Technology Project(Grant No.2017RC007)Key Project of Zhejiang Province Ministry of Science and Technology(Grant No.2015C03055)Talent Project of Zhejiang Association for Science and Technology(Grant No.2017YCGC002)Zhejiang Province Science and Technology Project of TCM(Grant No.2019ZZ016)Key Project of Hangzhou Ministry of Science and Technology(Grant No.20162013A07,20142013A63)Zhejiang Provincial Project for the Key Discipline of Traditional Chinese Medicine(Grant No.2017-XK-A09)。
文摘Objective:This study aimed to develop a new polyethylene glycol(PEG)ylatedβ-elemene liposome(PEG-Lipo-β-E)and evaluate its characterization,pharmacokinetics,antitumor effects and safety in vitro and in vivo.Methods:The liposomes were prepared by ethanol injection and high-pressure micro-jet homogenization.Characterization of the liposomes was conducted,and drug content,entrapment efficiency(EE),in vitro release and stability were studied by ultra-fast liquid chromatography(UFLC)and a liquid surface method.Blood was drawn from rats to establish the pharmacokinetic parameters.The anticancer effect was evaluated in a KU-19-19 bladder cancer xenograft model.Histological analyses were performed to evaluate safety.Results:The PEG-Lipo-β-E showed good stability and was characterized as 83.31±0.181 nm in size,0.279±0.004 in polydispersity index(PDI),-21.4±1.06 mV in zeta potential,6.65±0.02 in pH,5.024±0.107 mg/mL inβ-elemene(β-E)content,and 95.53±1.712%in average EE.The Fourier transform infrared spectroscopy(FTIR)and differential scanning calorimetry(DSC)indicated the formation of PEG-Lipo-β-E.Compared to elemene injection,PEG-Lipo-β-E demonstrated a 1.75-fold decrease in clearance,a 1.62-fold increase in half-life,and a 1.76-fold increase in area under the concentration-time curves(AUCs)from 0 hour to 1.5 hours(P<0.05).PEG-Lipo-β-E also showed an enhanced anticancer effect in vivo.Histological analyses showed that there was no evidence of toxicity to the heart,kidney,liver,lung or spleen.Conclusions:The present study demonstrates PEG-Lipo-β-E as a new formulation with ease of preparation,high EE,good stability,improved bioavailability and antitumor effects.
基金supported by National Natural Science Foundation of China (81102394)Natural Science Foundation of Liaoning Province (20170540575)
文摘This study aimed to investigate the ability of the novel materials D-α-tocopheryl poly(2-ethyl-2-oxazoline) succinate(TPOS) to construct pH-sensitive liposomes. TPOS was initially synthesized and characterized by TLC, FTIR, and ~1H-NMR. The buffering capacity of polyethylene glycol-distearoyl phosphatidylethanolamine(PEG-DSPE) and TPOS was determined by acid-base titration, and TPOS displayed a slower downtrend and gentler slope of titration curve than PEG-DSPE within pH 7.4–5.0. Studies on the in vitro drug release demonstrated that TPOS modified docetaxel(DOC) liposomes(TPOS-DOC-L) had a slower drugrelease rate at pH 7.4 similar to PEGylated-DOC liposomes(PEG-DOC-L), whereas the release rate reached approximately 86.92% ± 1.69% at pH 6.4. In vitro cellular uptake assays by microplate reader, and flow cytometry revealed that TPOS modified coumarin 6 liposomes(TPOS-C6-L) had stronger cellular uptake at pH 6.4 than that at pH 7.4( P < 0.01). Conversely, for PEGylated C6 liposomes(PEG-C6-L) and conventional C6 liposomes(C6-L), very similar cellular uptakes were exhibited at different pH values. Confocal laser scanning microscopy images showed that PEG-C6-L and C6-L were mainly located in lysosomes. By contrast, TPOS-C6-L showed broader cytoplasmic release and distribution at 4 h. MTT assay showed that the cytotoxicity of TPOS-DOC-L was similar to that of PEG-DOC-L and conventional DOC liposomes(DOC-L) at the same DOC concentration and at pH 7.4, but was much lower than those at pH 6.4 after 48 h of incubation. The apoptosis of PEG-DOC-L and DOC-L had no remarkable improvement with decreased pH from 7.4 to 6.4. Meanwhile, TPOS-DOC-Lsignificantly induced the apoptosis of HeLa cells with decreased pH. Therefore, TPOS can be a biomaterial for the construction of a pH-sensitive drug delivery system.
文摘There is now little doubt that PEGylation is useful and is in widespread use because it provides a prolonged half-life,a higher stability and a lowerimmunogenicity[1].However,it is of concern that PEGylation may affect the physicochemical and pharmacokinetic characteristics of protein-encapsulated liposome.Thus,we prepared the bovine serum albumin(BSA)-encapsulated liposome(BSA-liposome)with or without PEG and then compared their physicochemical and pharmacokinetic characteristics(Fig.1).BSA-liposomes were prepared by the thin-film hydration method.
文摘For systemic injection of cationic liposome/plasmid DNA (pDNA) complexes (cationic lipoplexes), polyethylene glycol (PEG)-modification (PEGylation) of lipoplexes can enhance their systemic stability. In this study, we examined whether intravenous injection of PEGylated cationic lipoplexes into tumor-bearing mice could deliver pDNA into tumor tissues and induce transgene expression. PEGylation of cationic liposomes could prevent their agglutination with erythrocytes. However, when PEGylated cationic lipoplexes were injected intravenously into tumor-bearing mice, they accumulated in tumor vascular vessels and did not exhibit transgene expression in tumors with both poor and well-developed vascularization. Furthermore, PEGylated cationic lipoplexes of CpG- free pDNA could not increase transgene expression in tumors after intravenous injection. These results suggested that PEGylation could not extravasate cationic lipoplexes from vascular vessels in tumors and abolished transgene expression although it enhanced the systemic stability of cationic lipoplexes by avoiding interactions with blood components such as erythrocytes. Successful delivery of pDNA to tumors by PEGylated cationic liposomes will require a rational strategy and the design of liposomal delivery systems to overcome the issue associated with the use of PEG.
基金Supported by National Natural Science Foundation of China(CN):Vascular Normalization by Huoxuehuayu medicine Induces decrease of the Interstitial Fluid and Improves Drug Penetration in Tumors(No.81202784)
文摘OBJECTIVE: To investigate whether the Tandistribution and anti-tumor Ⅱef A could improve the ficacy of Pegylated Liposomal Doxorubicin(PLD) via normalizing the structure and function of vasculature in Hepa1-6 hepatoma mice model.METHODS: Hepa1-6 hepatoma-bearing mice were treated with TanⅡA for 14 d. Distribution and anti-tumor efficacy of PLD, and the structure and function of the tumor vasculature were evaluated using various techniques.RESULTS: TanⅡ A significantly reduced the micro-vessel density(MVD). After Tan vascular walls were betteⅡr s A treatment,the tumor tructured, as the increased coverage of the pericytes and the promoted contact of the basement membrane and endothelial cell. Functional tests showed that tumor hypoxia was improved and the exudation amount of Evans blue in the parenchyma of the tumor decreased. In addition, mice treated with TanA had greater PLD penetration distance intratumoⅡrally. Furthermore, combined therapy of Tanibited tumor growth.ⅡA and PLD significantly inhCONCLUSION: This study suggests that Tanasculature andⅡ h A helps normalizing the tumor vas therapeutic potential in increasing the distribution of chemotherapy drug in the tumor.
文摘Alzheimer’s disease is a neurodegenerative condition leading to atrophy of the brain and robbing nearly 5.8 million individuals in the United States age 65 and older of their cognitive functions.Alzheimer’s disease is associated with dementia and a progressive decline in memory,thinking,and social skills,eventually leading to a point that the individual can no longer perform daily activities independently.Currently available drugs on the market temporarily alleviate the symptoms,however,they are not successful in slowing down the progression of Alzheimer’s disease.Treatment and cures have been constricted due to the difficulty of drug delivery to the blood-brain barrier.Several studies have led to identification of vesicles to transport the necessary drugs through the blood-brain barrier that would typically not achieve the targeted area through systemic delivered medications.Recently,liposomes have emerged as a viable drug delivery agent to transport drugs that are not able to cross the blood-brain barrier.Liposomes are being used as a component of nanoparticle drug delivery;due to their biocompatible nature;and possessing the capability to carry both lipophilic and hydrophilic therapeutic agents across the blood brain barrier into the brain cells.Studies indicate the importance of liposomal based drug delivery in treatment of neurodegenerative disorders.The idea is to encapsulate the drugs inside the properly engineered liposome to generate a response of treatment.Liposomes are engineered to target specific diseased moieties and also several surface modifications of liposomes are under research to create a clinical path to the management of Alzheimer’s disease.This review deals with Alzheimer’s disease and emphasize on challenges associated with drug delivery to the brain,and how liposomal drug delivery can play an important role as a drug delivery method for the treatment of Alzheimer’s disease.This review also sheds some light on variation of liposomes.Additionally,it emphasizes on the liposomal formulations which are currently researched or used for treatment of Alzheimer’s disease and also discusses the future prospect of liposomal based drug delivery in Alzheimer’s disease.
文摘Purpose: To explore the preventive effect of Regional cooling comprehensive nursing on hand foot syndrome caused by pegylated liposomal doxorubicin (PLD). Method: Adopt overall sampling method. Patients who used the same adjuvant drugs from January to December 2020 were randomly divided into an intervention group and a control group. The patients in the two groups received routine nursing guidance and drug prevention for the use of amygdalin. The patients in the intervention group were required to take protective measures of Regional cooling during chemotherapy. The occurrence of hand foot syndrome during adriamycin liposome administration was compared between the two groups. Results: By comparing the adverse reactions of cases during Adriamycin Administration, the incidence rates of grade I, II and III hand foot syndrome in the control group were 28.8%, 7.6% and 27.5% respectively, and the incidence rates of grade I, II and III hand foot syndrome in the intervention group were 42.1%, 12.3% and 7.0% respectively, with statistical significance (P Conclusion: Regional cooling nursing and preventive behavior guidance can effectively reduce the severity of hand foot syndrome caused by adriamycin.