The purpose of this study was to evaluate the efficacy and safety of nanoparticle albumin-bound paclitaxel as a rescue regimen in the treatment of patients with advanced non-small-cell lung cancer. We retrospectively ...The purpose of this study was to evaluate the efficacy and safety of nanoparticle albumin-bound paclitaxel as a rescue regimen in the treatment of patients with advanced non-small-cell lung cancer. We retrospectively reviewed the medical records of 20 patients with stage IV non-small-cell lung cancer. The patients had progressive disease after standard antitumor therapy and subsequently received intravenous albumin-bound paclitaxel at the dose of 100 mg/m2 in weekly schedule. Cumulative findings showed that the overall response rate was 30.0%, the disease control rate amounted to 40%, and the 1 year survival rate was 30%. In addition, the median time to progression and the median survival time reached 5 and 10 months, respectively. Meanwhile, no severe hypersensitivity reactions and grade 4 adverse effects were reported. In summary, weekly-administered albumin-bound paclitaxel seems to be an effective and safe regimen for elderly patients with stage IV non-small-cell lung cancer who were refractory to conventional therapy.展开更多
BACKGROUND The advanced first-line regimen for advanced gastric cancer is based on a combination of fluoropyrimidine and platinum and/or paclitaxel(PTX),forming a two-or three-drug regimen.Compared to conventional PTX...BACKGROUND The advanced first-line regimen for advanced gastric cancer is based on a combination of fluoropyrimidine and platinum and/or paclitaxel(PTX),forming a two-or three-drug regimen.Compared to conventional PTX,nanoparticle albumin-bound PTX(Nab-PTX)has better therapeutic effects and fewer adverse effects reported in studies.Nab-PTX is a great option for patients presenting with advanced gastric cancer.Herein,we highlight an adverse event(hemorrhagic cystitis)of Nab-PTX in advanced gastric cancer.CASE SUMMARY A 55-year-old male was diagnosed with lymph node metastasis after a laparo-scopic-assisted radical gastrectomy for gastric cancer that was treated by Nab-PTX and S-1(AS).On the 15th day after treatment with AS,he was diagnosed with hemorrhagic cystitis.CONCLUSION Physicians should be aware that hemorrhagic cystitis is a potential adverse event associated with Nab-PTX treatment.展开更多
Albumin nanoparticles are considered to be an effective way to load water-insoluble anticancer drugs and target tumors via the gp60-mediated pathway. Herein, we fabricated an albumin nanoparticle formulation for co-lo...Albumin nanoparticles are considered to be an effective way to load water-insoluble anticancer drugs and target tumors via the gp60-mediated pathway. Herein, we fabricated an albumin nanoparticle formulation for co-loading paclitaxel(PTX) and curcumin(CCM), both of which have prominent anticancer efficacy, via nanoparticle albumin-bound(NabTM) technology using high-pressure homogenization. The PTX/CCM co-bound albumin nanoparticles(PTX/CCM Alb-NPs) had a slightly greater particle size of ~250 nm than that of plain PTX AlbNPs and CCM Alb-NPs(~234 and ~134 nm, respectively), with spherical surface morphology and stable size maintenance. However, the zeta potential of PTX/CCM Alb-NPs(ca.-30 mV)was not significantly different from that of PTX or CCM Alb-NPs. The loaded PTX and CCM were released gradually from the PTX/CCM Alb-NPs over ~24 h(97.7 ± 1.7% and 76.2 ± 0.5%,respectively). Furthermore, PTX/CCM Alb-NPs appeared to be efficiently internalized into Mia Paca-2 cells and exhibited a 71% increased IC50 versus PTX Alb-NPs in terms of cytotoxicity to Mia Paca-2 cells. These results suggest that PTX/CCM Alb-NPs are a new potential anticancer agent for combination therapy.展开更多
Drug resistance is a great challenge in cancer therapy using chemotherapeutic agents. Administration of these drugs with siRNA is an efficacious strategy in this battle. Here, the present study tried to incorporate si...Drug resistance is a great challenge in cancer therapy using chemotherapeutic agents. Administration of these drugs with siRNA is an efficacious strategy in this battle. Here, the present study tried to incorporate siRNA and paclitaxel(PTX) simultaneously into a novel nanocarrier. The selectivity of carrier to target cancer tissues was optimized through conjugation of folic acid(FA) and glucose(Glu) onto its surface. The structure of nanocarrier was formed from ternary magnetic copolymers based on FeCopolyethyleneimine(FeCo-PEI) nanoparticles and polylactic acid-polyethylene glycol(PLA-PEG) gene delivery system. Biocompatibility of FeCo-PEI-PLA-PEG-FA(NPsA), FeCo-PEI-PLA-PEG-Glu(NPsB) and FeCo-PEI-PLA-PEG-FA/Glu(NPsAB) nanoparticles and also influence of PTX-loaded nanoparticles on in vitro cytotoxicity were examined using MTT assay. Besides, siRNA-FAM internalization was investigated by fluorescence microscopy. The results showed the blank nanoparticles were significantly less cytotoxic at various concentrations. Meanwhile, siRNA-FAM/PTX encapsulated nanoparticles exhibited significant anticancer activity against MCF-7 and BT-474 cell lines. NPsAB/siRNA/PTX nanoparticles showed greater effects on MCF-7 and BT-474 cells viability than NPsA/siRNA/PTX and NPsB/siRNA/PTX.Also, they induced significantly higher anticancer effects on cancer cells compared with NPsA/siRNA/PTX and NPsB/siRNA/PTX due to their multi-targeted properties using FA and Glu. We concluded that NPsAB nanoparticles have a great potential for co-delivery of both drugs and genes for use in gene therapy and chemotherapy.展开更多
Poly(2-oxazoline)(POx)has been regarded as a potential candidate for drug delivery carrier to meet the challenges of nanomedicine clinical translation,due to its excellent biocompatibility and self-assembly properties...Poly(2-oxazoline)(POx)has been regarded as a potential candidate for drug delivery carrier to meet the challenges of nanomedicine clinical translation,due to its excellent biocompatibility and self-assembly properties.The drug loading capacity and stability of amphiphilic POxs as drug nanocarriers,however,tend to be insufficient.Herein,we report a strategy to prepare nucleobase-crosslinked POx nanoparticles(NPs)with enhanced stability and ultra-high paclitaxel(PTX)loading capacity for breast cancer therapy.An amphiphilic amine-functionalized POx(PMBEOx-NH_(2))was firstly prepared through a click reaction between cysteamines and vinyl groups in poly(2-methyl-2-oxazoline)-block-poly(2–butyl–2-oxazoline-co-2-butenyl-2-oxazoline)(PMBEOx).Complementary nucleobase-pairs adenine(A)and uracil(U)were subsequently conjugated to PMBEOx-NH2 to give functional POxs(POxA and POxU),respectively.Due to the nucleobase interactions formed between A and U,NPs formed by POxA and POxU at a molar ratio of 1:1 displayed ultrahigh PTX loading capacity(38.2%,PTX/POxA@U),excellent stability,and reduced particle size compared to the uncross-linked PTX-loaded NPs(PTX/PMBEOx).Besides the prolonged blood circulation and enhanced tumor accumulation,the smaller PTX/POxA@U NPs also have better tumor penetration ability compared with PTX/PMBEOx,thus leading to a higher tumor suppression rate in two murine breast cancer models(E0711 and 4T1).These results proved that the therapeutic effect of chemotherapeutic drugs could be improved remarkably through a reasonable optimization of nanocarriers.展开更多
Cholesterol-core nanoparticles （LDE） have been shown to be recognized by low-density lipoprotein receptors （LDLR） after administration; therefore, LDE is an ideal vehicle to deliver drug with targeting property. P...Cholesterol-core nanoparticles （LDE） have been shown to be recognized by low-density lipoprotein receptors （LDLR） after administration; therefore, LDE is an ideal vehicle to deliver drug with targeting property. Paclitaxel, when incorporated into LDE, promotes atherosclerosis regression with reduced drug toxicity in rabbits through LDLR. Here, we tested whether LDE-paclitaxel could still be effective in reducing diet-induced atherosclerosis in a mouse model without LDLR. Nineteen LDLR knockout male mice were fed 1% cholesterol for 12 weeks. Then, 12 animals received 4-weekly intraperitoneal LDE-paclitaxel （4 mg/kg） while 7 controls received saline solution. On week 12 and 16, in vivo MR/of the aortic roots was performed. Aorta macroscopy was made after euthanasia. Reduction ofatherosclerotic lesions was observed. LDE-paclitaxel treatment resulted in reduction of wall area （14%） and stenosis （22%） by MR/and 33% by macroscopy. Thus, LDE-paclitaxel may produce pharmacological effects through LDE uptake by mechanisms other than LDLR.展开更多
Objective: The aim of this trial was to compare both the efficacy and the safety of a weekly nanoparticle albumin-bound paclitaxel(nab-paclitaxel) plus cisplatin vs. gemcitabine plus cisplatin in patients with advance...Objective: The aim of this trial was to compare both the efficacy and the safety of a weekly nanoparticle albumin-bound paclitaxel(nab-paclitaxel) plus cisplatin vs. gemcitabine plus cisplatin in patients with advanced non-small-cell lung cancer(NSCLC).Methods: A total of 84 participants received either 100 mg/m^2 nab-paclitaxel each week on d 1, 8 and 15 of a 28 day cycle, as well as cisplatin 75 mg/m^2 on d 1 every three weeks(nab-TP arm); or gemcitabine 1,000 mg/m^2 on d 1 and 8, plus cisplatin 75 mg/m^2 on d 1 every three weeks(GP arm). The primary end point was progression-free survival(PFS). The secondary end points were overall response rate(ORR) and overall survival(OS).Results: According to our analysis, the median PFS was 4.8 months for the nab-TP arm vs. 5.2 months for the GP arm(P=0.55). Analysis showed the median OS was 14.6 months for participants who were in the nab-TP arm vs. 15.1 months for those in the GP arm(P=0.94). Besides, nab-TP showed OS advantages over GP in patients harboring epidermal growth factor receptor(EGFR) mutation(26.7 vs. 15.3 months, P=0.046) and patients with a performance status of 0(23.5 vs. 14.7 months, P=0.020). It was found that incidences of drug-related grade 3 or 4 toxicities were comparable between the two treatment arms.Conclusions: Therefore, it can be seen that weekly nab-TP treatment has a similar efficacy and tolerability to GP treatment for patients who are undergoing their first-line treatment for NSCLC. It could be that survival differences among platinum doublets in the context of both EGFR mutation and performance status have the potential to be the basis for our further clinical trials.展开更多
Objective： To observe the efficacy and safety of albumin-bound paclitaxel （ABP） monotherapy in treating recurrent advanced non-small-cell lung cancer （NSCLC）. Methods： We retrospectively analyzed the short-term ...Objective： To observe the efficacy and safety of albumin-bound paclitaxel （ABP） monotherapy in treating recurrent advanced non-small-cell lung cancer （NSCLC）. Methods： We retrospectively analyzed the short-term efficacy and toxicities of ABP monotherapy in treating 21 patients who had previously undergone multiple cycles of therapy for their advanced NSCLC in our hospital since 2010. The treatment-related survival was also analyzed. Results： Of these 21 patients, the best overall response was partial response （PR） in 6 patients （28.6%）, stable disease （SD） in I0 patients （47.6%）, and progressive disease （PD） in 5 patients （23.8%）. The overall response rate （ORR） was 28.6% and the disease control rate （DCR） （PR ＋ SD） was 76.2%. The median progression-flee survival （PFS） was 4.0 months （95% CI, 5.0-7.0 months）. The main grade 3/4 toxicities included neutropenia （11.1%）, peripheral nerve toxicity （5.6%）, muscle and joint aches （5.6%）, and fatigue （5.6%）. Conclusions： The ABP monotherapy can achieve good objective response in advanced NSCLC patients who have previously received multiple cycles of treatment and be well tolerated.展开更多
BACKGROUND Cholangiocarcinomas are rare and very aggressive tumors.Most patients have advanced-stage or unresectable disease at presentation,and the systemic therapies have limited efficacy.Albumin-bound paclitaxel(na...BACKGROUND Cholangiocarcinomas are rare and very aggressive tumors.Most patients have advanced-stage or unresectable disease at presentation,and the systemic therapies have limited efficacy.Albumin-bound paclitaxel(nab-paclitaxel)is a solvent-free taxane that has been approved for the treatment of some cancers such as breast,non-small cell lung and pancreatic cancer,however it has not been applied to treat cholangiocarcinoma.We have both preclinical and clinical evidence of the efficacy of nab-paclitaxel in cholangiocarcinoma,yet no phase 3 trials have been made.CASE SUMMARY A 63-year-old man was diagnosed in December 2016 with stage III B intrahepatic cholangiocarcinoma.Surgery was performed,followed by adjuvant chemotherapy treatment with capecitabine and gemcitabine;although,the gemcitabine was suspended due to allergic reaction after two cycles.In April 2019,metastatic cholangiocarcinoma relapse was diagnosed,and a first-line treatment with FOLFOX scheme was started.Eight cycles were administered,producing an initial clinical improvement and decrease in blood tumor marker levels.Radiological and serological progression was noted in September 2019.As a second-line treatment,FOLFIRI was not recommended due to risk of worsening the patient’s tumor-related diarrhea.A combination therapy with gemcitabine was not feasible,as the patient had previously suffered from an allergic reaction to this treatment.We decided to use nab-paclitaxel as a second-line treatment,and four cycles were administered.Both clinical and serological responses were observed,and a radiological mixed response was also noted.CONCLUSION Advanced cholangiocarcinoma could be treated with nab-paclitaxel monotherapy,which should be studied in combination with other types of treatment(chemotherapy,fibroblast growth factor receptor inhibitors).展开更多
目的:了解白蛋白紫杉醇(Nanoparticle Albumin Bound Paclitaxel,NAB-PTX)在医保患者中的临床使用以及报销情况,为NAB-PTX纳入医保支付后的报销管理提供参考。方法:结合《国家基本医疗保险、工伤保险和生育保险药品目录》(简称:《药品...目的:了解白蛋白紫杉醇(Nanoparticle Albumin Bound Paclitaxel,NAB-PTX)在医保患者中的临床使用以及报销情况,为NAB-PTX纳入医保支付后的报销管理提供参考。方法:结合《国家基本医疗保险、工伤保险和生育保险药品目录》(简称:《药品目录》),分析研究单位2021年9月至2022年2月NAB-PTX医保患者的临床使用及医保报销数据。对患者特征、疾病分布、药品用量、医保报销情况等进行描述性统计分析。采用Mann-Whiney U检验比较乳腺恶性肿瘤患者中NAB-PTX是否纳入报销对患者费用负担的影响。结果:医保患者使用NAB-PTX人次排名前三的疾病为乳腺恶性肿瘤、肺恶性肿瘤、食管恶性肿瘤。215人次符合医保支付条件,占使用总人次的7.19%。乳腺恶性肿瘤患者使用NAB-PTX排名前三的情况为乳腺癌术后辅助化疗、乳腺癌术前新辅助治疗、联合化疗失败的转移性乳腺癌。NAB-PTX纳入报销的患者自付费用与NAB-PTX未纳入报销的患者差异较大。结论:NAB-PTX在恶性肿瘤的治疗中应用广泛,2021年《药品目录》报销的覆盖范围有限,2022年《药品目录》取消NAB-PTX支付适应症限定后需要结合药品集中带量采购政策做好药物经济学评价以及基金支出预算分析。展开更多
Despite great therapeutic effect of Abraxane®,complex preparation technology and unfavorable pharmacokinetics still restricted the clinical application of albumin-based paclitaxel(PTX)nanoparticles(NPs).Herein,we...Despite great therapeutic effect of Abraxane®,complex preparation technology and unfavorable pharmacokinetics still restricted the clinical application of albumin-based paclitaxel(PTX)nanoparticles(NPs).Herein,we reported that an albumin-binding prodrug,phenylboronic acid-conjugated PTX(P-PTX),can form the uniform NPs with the diameters around 100 nm with the help of albumin via simple one-step nano-precipitation method.The albumin-based nanomedicines were stabilized by the integration of a single boronic acid with PTX due to the increased affinity based on multiple intermolecular interactions.We found that albumin-based P-PTX NPs exhibited superior colloidal stability over albumin-based PTX NPs through one-step nanoprecipitation approach,achieving longer in vivo circulation time and higher concentration in tumor than those of the marketed Abraxane®.Furthermore,the albumin-based P-PTX NPs with great stability and enhanced intratumoral enrichment,increased the maximum tolerated dose of PTX,remarkably suppressed the growth of breast tumor and lung metastasis,prolonged survival of melanoma tumors-bearing mice.Such a convenient and effective system gains an insight into the impact of phenylboronic acid group on the albumin-based PTX NPs,provides potent strategy for the rational design of albumin-based antitumor nanomedicines.展开更多
Structure-efficacy effect of small molecular drug attracts wide attentions,but it has always been ignored in nanomedicine research.To reveal the efficacy modulation of nanomedicine,we developed a new type of paclitaxe...Structure-efficacy effect of small molecular drug attracts wide attentions,but it has always been ignored in nanomedicine research.To reveal the efficacy modulation of nanomedicine,we developed a new type of paclitaxel(PTX)-conjugated gold nanoparticles(PTX-co njugated GNPs)to investigate the influence of drug position in controlling their in vitro properties and in vivo performance.Two therapeutic ligands(TA-PEG-NH-N=PTX and TA-PTX=N-NH-PEG)were synthesized to conjugate PTX on the surface of GNPs at different positions,locating on the surface of gold conjugate and inserting between GNPs and polyethylene glycol(PEG,molecular weight 1000 Da),respectively.It was found that PEG-PTX@GNPs with PTX located between GNP and PEG exhibited higher aqueous solubility,biocompatibility,and stability.In addition,an acid sensitive hydrazone bond has been inserted between PTX and PEG in both ligands for drug release of PTX and PTX-PEG segment,respectively,at the tumor site.Further release of PTX from PTX-PEG segment is based on the esterase hydrolysis of an ester bond between PTX and PEG.This two-step drug release mechanism offers PEG-PTX@GNPs effective and sustained release behavior for desirable anticancer activity,enhanced therapeutic efficacy,and lower systematic toxicity in Hepsbearing animal models.展开更多
文摘The purpose of this study was to evaluate the efficacy and safety of nanoparticle albumin-bound paclitaxel as a rescue regimen in the treatment of patients with advanced non-small-cell lung cancer. We retrospectively reviewed the medical records of 20 patients with stage IV non-small-cell lung cancer. The patients had progressive disease after standard antitumor therapy and subsequently received intravenous albumin-bound paclitaxel at the dose of 100 mg/m2 in weekly schedule. Cumulative findings showed that the overall response rate was 30.0%, the disease control rate amounted to 40%, and the 1 year survival rate was 30%. In addition, the median time to progression and the median survival time reached 5 and 10 months, respectively. Meanwhile, no severe hypersensitivity reactions and grade 4 adverse effects were reported. In summary, weekly-administered albumin-bound paclitaxel seems to be an effective and safe regimen for elderly patients with stage IV non-small-cell lung cancer who were refractory to conventional therapy.
文摘BACKGROUND The advanced first-line regimen for advanced gastric cancer is based on a combination of fluoropyrimidine and platinum and/or paclitaxel(PTX),forming a two-or three-drug regimen.Compared to conventional PTX,nanoparticle albumin-bound PTX(Nab-PTX)has better therapeutic effects and fewer adverse effects reported in studies.Nab-PTX is a great option for patients presenting with advanced gastric cancer.Herein,we highlight an adverse event(hemorrhagic cystitis)of Nab-PTX in advanced gastric cancer.CASE SUMMARY A 55-year-old male was diagnosed with lymph node metastasis after a laparo-scopic-assisted radical gastrectomy for gastric cancer that was treated by Nab-PTX and S-1(AS).On the 15th day after treatment with AS,he was diagnosed with hemorrhagic cystitis.CONCLUSION Physicians should be aware that hemorrhagic cystitis is a potential adverse event associated with Nab-PTX treatment.
文摘Albumin nanoparticles are considered to be an effective way to load water-insoluble anticancer drugs and target tumors via the gp60-mediated pathway. Herein, we fabricated an albumin nanoparticle formulation for co-loading paclitaxel(PTX) and curcumin(CCM), both of which have prominent anticancer efficacy, via nanoparticle albumin-bound(NabTM) technology using high-pressure homogenization. The PTX/CCM co-bound albumin nanoparticles(PTX/CCM Alb-NPs) had a slightly greater particle size of ~250 nm than that of plain PTX AlbNPs and CCM Alb-NPs(~234 and ~134 nm, respectively), with spherical surface morphology and stable size maintenance. However, the zeta potential of PTX/CCM Alb-NPs(ca.-30 mV)was not significantly different from that of PTX or CCM Alb-NPs. The loaded PTX and CCM were released gradually from the PTX/CCM Alb-NPs over ~24 h(97.7 ± 1.7% and 76.2 ± 0.5%,respectively). Furthermore, PTX/CCM Alb-NPs appeared to be efficiently internalized into Mia Paca-2 cells and exhibited a 71% increased IC50 versus PTX Alb-NPs in terms of cytotoxicity to Mia Paca-2 cells. These results suggest that PTX/CCM Alb-NPs are a new potential anticancer agent for combination therapy.
基金supported by the Deputy Research and Technology, Ardabil University of Medical Sciences。
文摘Drug resistance is a great challenge in cancer therapy using chemotherapeutic agents. Administration of these drugs with siRNA is an efficacious strategy in this battle. Here, the present study tried to incorporate siRNA and paclitaxel(PTX) simultaneously into a novel nanocarrier. The selectivity of carrier to target cancer tissues was optimized through conjugation of folic acid(FA) and glucose(Glu) onto its surface. The structure of nanocarrier was formed from ternary magnetic copolymers based on FeCopolyethyleneimine(FeCo-PEI) nanoparticles and polylactic acid-polyethylene glycol(PLA-PEG) gene delivery system. Biocompatibility of FeCo-PEI-PLA-PEG-FA(NPsA), FeCo-PEI-PLA-PEG-Glu(NPsB) and FeCo-PEI-PLA-PEG-FA/Glu(NPsAB) nanoparticles and also influence of PTX-loaded nanoparticles on in vitro cytotoxicity were examined using MTT assay. Besides, siRNA-FAM internalization was investigated by fluorescence microscopy. The results showed the blank nanoparticles were significantly less cytotoxic at various concentrations. Meanwhile, siRNA-FAM/PTX encapsulated nanoparticles exhibited significant anticancer activity against MCF-7 and BT-474 cell lines. NPsAB/siRNA/PTX nanoparticles showed greater effects on MCF-7 and BT-474 cells viability than NPsA/siRNA/PTX and NPsB/siRNA/PTX.Also, they induced significantly higher anticancer effects on cancer cells compared with NPsA/siRNA/PTX and NPsB/siRNA/PTX due to their multi-targeted properties using FA and Glu. We concluded that NPsAB nanoparticles have a great potential for co-delivery of both drugs and genes for use in gene therapy and chemotherapy.
基金financially supported by the National Natural Science Foundation of China (51973215, 52025035, 52103194, 22105199, 51829302)Bureau of International Cooperation Chinese Academy of Science (121522KYSB20200029)the Youth Innovation Promotion Association of Chinese Academy of Sciences (2020232)
文摘Poly(2-oxazoline)(POx)has been regarded as a potential candidate for drug delivery carrier to meet the challenges of nanomedicine clinical translation,due to its excellent biocompatibility and self-assembly properties.The drug loading capacity and stability of amphiphilic POxs as drug nanocarriers,however,tend to be insufficient.Herein,we report a strategy to prepare nucleobase-crosslinked POx nanoparticles(NPs)with enhanced stability and ultra-high paclitaxel(PTX)loading capacity for breast cancer therapy.An amphiphilic amine-functionalized POx(PMBEOx-NH_(2))was firstly prepared through a click reaction between cysteamines and vinyl groups in poly(2-methyl-2-oxazoline)-block-poly(2–butyl–2-oxazoline-co-2-butenyl-2-oxazoline)(PMBEOx).Complementary nucleobase-pairs adenine(A)and uracil(U)were subsequently conjugated to PMBEOx-NH2 to give functional POxs(POxA and POxU),respectively.Due to the nucleobase interactions formed between A and U,NPs formed by POxA and POxU at a molar ratio of 1:1 displayed ultrahigh PTX loading capacity(38.2%,PTX/POxA@U),excellent stability,and reduced particle size compared to the uncross-linked PTX-loaded NPs(PTX/PMBEOx).Besides the prolonged blood circulation and enhanced tumor accumulation,the smaller PTX/POxA@U NPs also have better tumor penetration ability compared with PTX/PMBEOx,thus leading to a higher tumor suppression rate in two murine breast cancer models(E0711 and 4T1).These results proved that the therapeutic effect of chemotherapeutic drugs could be improved remarkably through a reasonable optimization of nanocarriers.
基金provided by a grant from Boston University,United States,Fundacao de Amparo à Pesquisa do Estado de Sao Paulo(FAPESP),Sao PauloConselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq),Brasília,Brazila scholarship from Coordena??o de Aperfeicoamento de Pessoal de Nível Superior-CAPES
文摘Cholesterol-core nanoparticles （LDE） have been shown to be recognized by low-density lipoprotein receptors （LDLR） after administration; therefore, LDE is an ideal vehicle to deliver drug with targeting property. Paclitaxel, when incorporated into LDE, promotes atherosclerosis regression with reduced drug toxicity in rabbits through LDLR. Here, we tested whether LDE-paclitaxel could still be effective in reducing diet-induced atherosclerosis in a mouse model without LDLR. Nineteen LDLR knockout male mice were fed 1% cholesterol for 12 weeks. Then, 12 animals received 4-weekly intraperitoneal LDE-paclitaxel （4 mg/kg） while 7 controls received saline solution. On week 12 and 16, in vivo MR/of the aortic roots was performed. Aorta macroscopy was made after euthanasia. Reduction ofatherosclerotic lesions was observed. LDE-paclitaxel treatment resulted in reduction of wall area （14%） and stenosis （22%） by MR/and 33% by macroscopy. Thus, LDE-paclitaxel may produce pharmacological effects through LDE uptake by mechanisms other than LDLR.
文摘Objective: The aim of this trial was to compare both the efficacy and the safety of a weekly nanoparticle albumin-bound paclitaxel(nab-paclitaxel) plus cisplatin vs. gemcitabine plus cisplatin in patients with advanced non-small-cell lung cancer(NSCLC).Methods: A total of 84 participants received either 100 mg/m^2 nab-paclitaxel each week on d 1, 8 and 15 of a 28 day cycle, as well as cisplatin 75 mg/m^2 on d 1 every three weeks(nab-TP arm); or gemcitabine 1,000 mg/m^2 on d 1 and 8, plus cisplatin 75 mg/m^2 on d 1 every three weeks(GP arm). The primary end point was progression-free survival(PFS). The secondary end points were overall response rate(ORR) and overall survival(OS).Results: According to our analysis, the median PFS was 4.8 months for the nab-TP arm vs. 5.2 months for the GP arm(P=0.55). Analysis showed the median OS was 14.6 months for participants who were in the nab-TP arm vs. 15.1 months for those in the GP arm(P=0.94). Besides, nab-TP showed OS advantages over GP in patients harboring epidermal growth factor receptor(EGFR) mutation(26.7 vs. 15.3 months, P=0.046) and patients with a performance status of 0(23.5 vs. 14.7 months, P=0.020). It was found that incidences of drug-related grade 3 or 4 toxicities were comparable between the two treatment arms.Conclusions: Therefore, it can be seen that weekly nab-TP treatment has a similar efficacy and tolerability to GP treatment for patients who are undergoing their first-line treatment for NSCLC. It could be that survival differences among platinum doublets in the context of both EGFR mutation and performance status have the potential to be the basis for our further clinical trials.
文摘Objective： To observe the efficacy and safety of albumin-bound paclitaxel （ABP） monotherapy in treating recurrent advanced non-small-cell lung cancer （NSCLC）. Methods： We retrospectively analyzed the short-term efficacy and toxicities of ABP monotherapy in treating 21 patients who had previously undergone multiple cycles of therapy for their advanced NSCLC in our hospital since 2010. The treatment-related survival was also analyzed. Results： Of these 21 patients, the best overall response was partial response （PR） in 6 patients （28.6%）, stable disease （SD） in I0 patients （47.6%）, and progressive disease （PD） in 5 patients （23.8%）. The overall response rate （ORR） was 28.6% and the disease control rate （DCR） （PR ＋ SD） was 76.2%. The median progression-flee survival （PFS） was 4.0 months （95% CI, 5.0-7.0 months）. The main grade 3/4 toxicities included neutropenia （11.1%）, peripheral nerve toxicity （5.6%）, muscle and joint aches （5.6%）, and fatigue （5.6%）. Conclusions： The ABP monotherapy can achieve good objective response in advanced NSCLC patients who have previously received multiple cycles of treatment and be well tolerated.
文摘BACKGROUND Cholangiocarcinomas are rare and very aggressive tumors.Most patients have advanced-stage or unresectable disease at presentation,and the systemic therapies have limited efficacy.Albumin-bound paclitaxel(nab-paclitaxel)is a solvent-free taxane that has been approved for the treatment of some cancers such as breast,non-small cell lung and pancreatic cancer,however it has not been applied to treat cholangiocarcinoma.We have both preclinical and clinical evidence of the efficacy of nab-paclitaxel in cholangiocarcinoma,yet no phase 3 trials have been made.CASE SUMMARY A 63-year-old man was diagnosed in December 2016 with stage III B intrahepatic cholangiocarcinoma.Surgery was performed,followed by adjuvant chemotherapy treatment with capecitabine and gemcitabine;although,the gemcitabine was suspended due to allergic reaction after two cycles.In April 2019,metastatic cholangiocarcinoma relapse was diagnosed,and a first-line treatment with FOLFOX scheme was started.Eight cycles were administered,producing an initial clinical improvement and decrease in blood tumor marker levels.Radiological and serological progression was noted in September 2019.As a second-line treatment,FOLFIRI was not recommended due to risk of worsening the patient’s tumor-related diarrhea.A combination therapy with gemcitabine was not feasible,as the patient had previously suffered from an allergic reaction to this treatment.We decided to use nab-paclitaxel as a second-line treatment,and four cycles were administered.Both clinical and serological responses were observed,and a radiological mixed response was also noted.CONCLUSION Advanced cholangiocarcinoma could be treated with nab-paclitaxel monotherapy,which should be studied in combination with other types of treatment(chemotherapy,fibroblast growth factor receptor inhibitors).
文摘目的:了解白蛋白紫杉醇(Nanoparticle Albumin Bound Paclitaxel,NAB-PTX)在医保患者中的临床使用以及报销情况,为NAB-PTX纳入医保支付后的报销管理提供参考。方法:结合《国家基本医疗保险、工伤保险和生育保险药品目录》(简称:《药品目录》),分析研究单位2021年9月至2022年2月NAB-PTX医保患者的临床使用及医保报销数据。对患者特征、疾病分布、药品用量、医保报销情况等进行描述性统计分析。采用Mann-Whiney U检验比较乳腺恶性肿瘤患者中NAB-PTX是否纳入报销对患者费用负担的影响。结果:医保患者使用NAB-PTX人次排名前三的疾病为乳腺恶性肿瘤、肺恶性肿瘤、食管恶性肿瘤。215人次符合医保支付条件,占使用总人次的7.19%。乳腺恶性肿瘤患者使用NAB-PTX排名前三的情况为乳腺癌术后辅助化疗、乳腺癌术前新辅助治疗、联合化疗失败的转移性乳腺癌。NAB-PTX纳入报销的患者自付费用与NAB-PTX未纳入报销的患者差异较大。结论:NAB-PTX在恶性肿瘤的治疗中应用广泛,2021年《药品目录》报销的覆盖范围有限,2022年《药品目录》取消NAB-PTX支付适应症限定后需要结合药品集中带量采购政策做好药物经济学评价以及基金支出预算分析。
基金the National Key Research and Development Program of China(No.2021YFA0909900)the National Natural Science Foundation of China(Nos.82073777 and 81803442)+1 种基金the General Project of Liaoning Provincial Department of Education(Nos.LJKZ0927 and LJKQZ2021034)the Natural Science Foundation of Liaoning Province(No.2022-BS-157).
文摘Despite great therapeutic effect of Abraxane®,complex preparation technology and unfavorable pharmacokinetics still restricted the clinical application of albumin-based paclitaxel(PTX)nanoparticles(NPs).Herein,we reported that an albumin-binding prodrug,phenylboronic acid-conjugated PTX(P-PTX),can form the uniform NPs with the diameters around 100 nm with the help of albumin via simple one-step nano-precipitation method.The albumin-based nanomedicines were stabilized by the integration of a single boronic acid with PTX due to the increased affinity based on multiple intermolecular interactions.We found that albumin-based P-PTX NPs exhibited superior colloidal stability over albumin-based PTX NPs through one-step nanoprecipitation approach,achieving longer in vivo circulation time and higher concentration in tumor than those of the marketed Abraxane®.Furthermore,the albumin-based P-PTX NPs with great stability and enhanced intratumoral enrichment,increased the maximum tolerated dose of PTX,remarkably suppressed the growth of breast tumor and lung metastasis,prolonged survival of melanoma tumors-bearing mice.Such a convenient and effective system gains an insight into the impact of phenylboronic acid group on the albumin-based PTX NPs,provides potent strategy for the rational design of albumin-based antitumor nanomedicines.
基金supported by grants from the National Natural Science Foundation of China(Nos.31870946,31470916,31500769 and 21705165)the Funding of Double First-rate Discipline Construction of China(No.CPU2018GF07)+1 种基金Priority Academic Program Development of Jiangsu Higher Education Institutionsthe Fundamental Research Funds for the Central Universities(Nos.2015PT036,2016PT014,and 3011900159)。
文摘Structure-efficacy effect of small molecular drug attracts wide attentions,but it has always been ignored in nanomedicine research.To reveal the efficacy modulation of nanomedicine,we developed a new type of paclitaxel(PTX)-conjugated gold nanoparticles(PTX-co njugated GNPs)to investigate the influence of drug position in controlling their in vitro properties and in vivo performance.Two therapeutic ligands(TA-PEG-NH-N=PTX and TA-PTX=N-NH-PEG)were synthesized to conjugate PTX on the surface of GNPs at different positions,locating on the surface of gold conjugate and inserting between GNPs and polyethylene glycol(PEG,molecular weight 1000 Da),respectively.It was found that PEG-PTX@GNPs with PTX located between GNP and PEG exhibited higher aqueous solubility,biocompatibility,and stability.In addition,an acid sensitive hydrazone bond has been inserted between PTX and PEG in both ligands for drug release of PTX and PTX-PEG segment,respectively,at the tumor site.Further release of PTX from PTX-PEG segment is based on the esterase hydrolysis of an ester bond between PTX and PEG.This two-step drug release mechanism offers PEG-PTX@GNPs effective and sustained release behavior for desirable anticancer activity,enhanced therapeutic efficacy,and lower systematic toxicity in Hepsbearing animal models.
