Efficacy and safety of transhepatic arterial chemoembolization with drug-loaded microspheres in unresectable primary liver cancer

BACKGROUND Transhepatic arterial chemoembolization(TACE),as a local treatment,has been widely used in the treatment of unresectable liver cancer.The introduction of drug carrier microspheres has brought new hope for the therapeutic effect of TACE.Microspheres can realize the slow release and directional delivery of drugs,reduce systemic toxicity and improve local curative effect.AIM To compare the effectiveness of traditional transcatheter arterial chemoembolization against microsphere-assisted transcatheter arterial chemoembolization in the treatment of hepatocellular carcinoma that is incurable.METHODS We searched the PubMed,Embase,Cochrane Library,and CNKI databases for clinical trials of drug-luting beads TACE(DEB-TACE)vs conventional TACE(cTACE)for the treatment of unresectable liver cancer.We screened references based on inclusion and exclusion criteria and then selected valid data for meta-analysis using RevMan 53 software.The complete response(CR)rate,partial response(PR)rate,postoperative stable disease(SD)rate,and 6-month and 12-month survival rates were compared.RESULTS A total of 12 articles were included,including 1177 patients,519 of whom received DEB-TACE and 658 of whom received cTACE.The CR rate in the DEB-TACE group was much greater than that in the cTACE group[relative risk(RR)=1.42,95%CI:1.18-1.72,P=0.0002].The 12-month survival rate significantly increased(RR=1.09;95%CI:1.01-1.17,P=0.03);the PR rate(RR=1.13;95%CI:0.97-1.30,P=0.12);the SD rate(RR=0.82;95%CI:0.64-1.05,P=0.12);and the 6-month survival rate(RR=1.05;95%CI:1.00-1.10,P=0.07).There was no significant difference(P<0.05).CONCLUSION Compared with those of iodized oil TACE,the drug-loaded microspheres tended to have therapeutic advantages.

The role of a drug-loaded poly(lactic co-glycolic acid)(PLGA) copolymer stent in the treatment of ovarian cancer

Objectives:Cisplatin(CDDP)is a widely used and effective basic chemotherapeutic drug for the treatment of a variety of tumors,including ovarian cancer.However,adverse side effects and acquired drug resistance are observed in the clinical application of CDDP.Identifying a mode of administration that can alleviate side effects and reduce drug resistance has become a promising strategy to solve this problem.Methods:In this study,3 D printing technology was used to prepare a CDDP-poly(lactic-co-glycolic acid)(CDDP-PLGA)polymer compound stent,and its physicochemical properties and cytotoxicity were evaluated both in vitro and in vivo.Results:The CDDP-PLGA stent had a significant effect on cell proliferation and apoptosis and clearly decreased the size of subcutaneous tumors in nude mice,whereas the systemic side effects were mild compared with those of intraperitoneal CDDP injection.Compared with the control group,CDDP-PLGA significantly increased the mRNA and protein levels of p-glycoprotein(P<0.01;P<0.01)and decreased vascular endothelial growth factor mRNA(P<0.05)and protein levels(P<0.01),however,CDDP-PLGA significantly decreased the mR NA and protein levels of p-glycoprotein(P<0.01;P<0.01)and vascular endothelial growth factor(P<0.01;P<0.01),which are associated with chemoresistance,in subcutaneous tumor tissue.Immunohistochemistry assay results revealed that,in the CDDP-PLGA group,the staining of the proliferation-related genes Ki67 and PCNA were lightly,and the apoptosis-related gene caspase-3 stained deeply.Conclusions:PLGA biomaterials loaded with CDDP,as compared with the same amount of free CDDP,showed good efficacy in terms of cytotoxicity,as evidenced by changes in apoptosis.Continuous local CDDP release can decrease the systemic side effects of this drug and the occurrence of drug resistance and angiogenesis,and improve the therapeutic effect.This new approach may be an effective strategy for the local treatment of epithelial ovarian cancer.

Evaluation of short-term effects of drug-loaded microspheres and traditional transcatheter arterial chemoembolization in the treatment of advanced liver cancer

BACKGROUND Liver cancer is a malignant tumor with high morbidity and mortality.Transcatheter arterial chemoembolization(TACE)is the main method for surgically unresectable liver cancer.In recent years,drug-loaded microspheres have been gradually applied in TACE technology.There are some controversies about the therapeutic effects of drug-loaded microspheres TACE(D-TACE)and traditional TACE.AIM To explore the short-term efficacy of D-TACE and traditional TACE in the treatment of advanced liver cancer.METHODS The clinical data of 73 patients with advanced liver cancer admitted to the First and Sixth Medical Centers of Chinese PLA General Hospital from January 2017 to October 2019 were retrospectively analyzed.Among them,15 patients were treated with D-TACE,and 58 patients were treated with traditional TACE.Clinical baseline characteristics,perioperative laboratory indices,postoperative adverse reactions and postoperative complications were compared between the two groups.RESULTS There was no statistical difference between the two groups for the postoperative response:The highest postoperative body temperature of the drug-loaded microsphere group was 38.0±0.9℃and the postoperative highest body temperature of the traditional TACE group was 38.3±0.7℃(t=-1.414,P=0.162).For the 24 h postoperative nausea and vomiting after surgery in terms of scoring and postoperative pain scores,the traditional TACE group was higher than the drugloaded microsphere group(χ2=14.33,P=0.014;χ2=32.967,P=0.000)and the two groups had significant statistical differences.The disease control rate at 3 mo after treatment in the drugloaded microsphere group was 60%and the disease control rate at 3 mo after treatment in the traditional TACE group was 75.9%(χ2=4.091,P=0.252).There was no statistical difference between the two groups of data.During the follow-up period,the number of interventional treatments received was once in the drug-loaded microsphere group and the traditional TACE group received an average of 1.48 treatments(χ2=10.444 P=0.005).There was a statistical difference between the two groups.CONCLUSION Compared with traditional TACE,D-TACE may have some advantages in the treatment of advanced hepatocellular carcinoma with a large tumor load in the short term,but the long-term clinical efficacy needs additional follow-up studies.In addition,compared with the traditional group,the patients in the drug-loaded microsphere group had better subjective tolerance and could reduce the number of interventional treatments.Therefore,D-TACE is worthy of clinical promotion.

Contact lens as an emerging platform for ophthalmic drug delivery:A systematic review

The number of people with eye diseases has increased with the use of electronics.However,the bioavailability of eye drops remains low owing to the presence of the ocular barrier and other reasons.Although many drug delivery systems have been developed to overcome these problems,they have certain limitations.In recent years,the development of contact lenses that can deliver drugs for long periods with high bioavailability and without affecting vision has increased the interest in using contact lenses for drug delivery.Hence,a review of the current state of research on drug delivery contact lenses has become crucial.This article reviews the key physical and chemical properties of drug-laden contact lenses,development and classification of contact lenses,and features of the commonly used materials.A review of the methods commonly used in current research to create contact lenses has also been presented.An overview on how drug-laden contact lenses can overcome the problems of high burst and short release duration has been discussed.Overall,the review focuses on drug delivery methods using smart contact lenses,and predicts the future direction of research on contact lenses.

Incorporation of Carvedilol into PAMAM-functionalized MWNTs as a sustained drug delivery system for enhanced dissolution and drug-loading capacity

The purpose of this study was to develop poly(amidoamine)(PAMAM)-functionalized multi-walled carbon nanotubes(MWNTs)loaded with a poorly water-soluble drug,intended to improve the drug-loading capacity,dissolution and design a sustained release system.MWNTs were modified with a carboxyl group by acid treatment and then complex with PAMAM.PAMAM-MWNTs were investigated as a scaffold for loading the model drug,Carvedilol(CAR),using three different methods(the fusion method,the incipient wetness impregnation method,and the solvent method).The effects of different pore size,specific surface area and physical state were systematically studied using FT-IR,TGA,SEM,DSC,nitrogen adsorption,XPS and XRD.All the samples made by PAMAM-MWNTs to load the drug had a marked effect on the drug-loading capacity as well as drug dissolution,especially theⅡ-30%.

Treatment of colorectal cancer by anticancer and antibacterial effects of hemiprotonic phenanthroline-phenanthroline^(+) with nanomicelle delivery

Colorectal cancer(CRC)is a common digestive tract tumor worldwide.Specific microorganisms,including Fusobacterium nucleatum(F.nucleatum)and Escherichia coli(E.coli),are abundant in colonic mucosa and can promote the cancer progression and malignancy.Therefore,a therapeutic strategy is proposed to deliver effective drugs to colorectum for both anticancer and antibacteria.Here we used thin-film dispersionmethod to encapsulate hemiprotonic phenanthroline-phenanthroline^(+)(ph-ph^(+))into nanomicelle.The results showed that the drug-loading nanomicelle had good dispersion,and the particle size was about 28 nm.In vitro assay indicated that the nanomicelle was active against CRC-related obligate and facultative anaerobes.In human CRC cells,the nanomicelle could effectively inhibit cell proliferation and induce apoptosis.In vivo distribution showed that the nanomicelle could release ph-ph^(+) mainly in the colorectum.In CRC model mice,the nanomicelle significantly reduced tumor number and volume,and decreased the bacteria load and colorectal inflammation.Together,the study identifies that the ph-ph^(+) nanomicelle has the potential to apply in treating CRC,and also suggests that anticancer combined with antimicrobial therapy would be a feasible way for CRC therapy.

Drug-loading ZIF-8 for modification of microporous bone scaffold to promote vascularized bone regeneration

Surface modification of microporous bone scaffolds using nanoparticles has been broadly studied in bone tissue engineering.Aiming at improving vascularized bone regeneration(VBR),zeolitic imidazolate framework-8(ZIF-8)was encapsulated with dimethyloxallyl glycine(DMOG)and the drug-carrying nanoparticles(D@Z)could be uniformly coated onto the surface of the bone scaffold.The osteogenic and angiogenic actions of D@Z are closely correlated with the amount of slowly released DMOG,and in general,exhibited a favorable association.Then,the D7.5@Z group,which showed the greatest capacity to induce in vitro osteogenesis-angiogenesis coupling,was utilized for surface modification of the bone scaffold.Biological processes including phosphate-containing compound metabolic process,cell differentiation,cell proliferation and cell motility might contribute to enhanced ability to induce VBR by the coated scaffold and signaling pathways such as Rap1,Ras,phosphatidylinositol 3-kinase/protein kinase B(PI3K-AKT)and vascular endothelial growth factor(VEGF)signaling pathways participated in these processes.Finally,as depicted by in vitro real time-polymerase chain reaction(RT-PCR),Western blot(WB)and in vivo cranial bone defect model,the microporous scaffold coated with nano-D7.5@Z greatly promoted VBR.To conclude,nano-D@Z has significant promise for practical application in modification of microporous bone scaffolds to enhance VBR,and DMOG loading quantity has a beneficial influence on D@Z to improve osteogenesis-angiogenesis coupling.

J-aggregation of photosensitizers leads to an ultrahigh drug-loading system for targeted delivery

Drug loading capacity is very important in the construction of targeted drug delivery systems(TDDSs)for the improvement of drug delivery efficiency.However,the drug-loading capacity of most nanomaterials is non-idealistic,and developing the high drug-loading TDDSs is still a critical challenge.In this work,an ultrahigh loading system(denoted as HMPB_(2))was prepared via J-aggregation of an aza-boron dipyrromethene derivative(Bod)by using hollow MnO_(2)modified with glucosamine pillar[5]arene as a carrier,which was demonstrated to have typical J-aggregate absorption of Bod,specific cancer cells targeting ability,negligible dark cytotoxicity,and potent phototoxicity.This work provides a successful example to construct an ultrahigh drug-loading system via J-aggregation for targeted delivery.

Efficacy of transcatheter arterial chemoembolization using pirarubicin-loaded microspheres combined with lobaplatin for primary liver cancer

BACKGROUND Drug-eluting beads show good safety and promising efficacy when used as part of a transarterial chemoembolization regimen for primary liver cancer.However,data on the clinical efficacy and safety of pirarubicin-loaded beads combined with lobaplatin are lacking in China.AIM To evaluate the efficacy and safety of transcatheter arterial chemoembolization using pirarubicin-loaded beads combined with lobaplatin for primary liver cancer.METHODS Between January 2019 and March 2020,60 patients with primary liver cancer were selected at Hebei North University Affiliated First Hospital.According to different treatment methods,the participants were categorized into two groups with 30 patients treated with pirarubicin-loaded microspheres combined with lobaplatin included in an observation group and 30 patients treated with pirarubicin emulsion with lipiodol combined with lobaplatin were included in a control group.The progression-free survival,overall survival,clinical response rate,disease control rate,liver and kidney function and adverse reactions were compared between the two groups.RESULTS The progression-free survival was 14 mo in the observation group,which was significantly higher than 9 mo of the control group(P<0.05).The 6-mo,12-mo and 18-mo survival rates were 93.33%(28/30),66.67%(20/30)and 23.33%(7/30),respectively in the observation group,which were significantly higher than 83.33%(25/30),50.00%(15/30)and 13.33%(4/30),respectively,of the control group(all P<0.05).The clinical efficacy rate and disease control rate were 73.33%and 93.33%,respectively,in the observation group,which were significantly higher than those of the control group(53.55%and 80.00%,respectively,all P<0.05).There was no significant difference in alpha-fetoprotein between the two groups before the treatment(P>0.05).After the treatment,alpha-fetoprotein was 289.06±76.21 ng/m L in the observation group and 365.01±73.11 ng/m L in the control group,which were low in both groups compared with those before the treatment(all P<0.05).The incidence of nausea and vomiting was significantly lower in the observation group than in the control group(P<0.05).There was no significant difference for the adverse reactions of pain and fever between the two groups(P<0.05).CONCLUSION The combination of pirarubicin-loaded beads and lobaplatin can improve treatment efficacy resulting in mild liver function damage and postoperative complications in patients with primary liver cancer.It can be used in clinical practice.

Efficacy of rhNGF-loaded amniotic membrane transplantation for rabbit corneal epithelial and nerve regeneration

AIM:To evaluate the efficacy of recombinant human nerve growth factor-loaded amniotic membrane(rh NGF-AM)on corneal epithelial and nerve regeneration in rabbit model.METHODS:Freshly prepared human amniotic membrane(AM)were immersed into PBS buffer containing 100 or 500μg/mL rh NGF for 15,30,and 60 min at 4℃.The in vitro release kinetics of rh NGF was measured with ELISA.For in vivo evaluation,the AM were immersed with 500μg/mL rh NGF for 30 min.Fifty-seven rabbits were selected to establish corneal epithelial defect model.In addition to the 19 rabbits in control group,38 rabbits received AM transplantation with or without rh NGF after the removal of central epithelium.Corneal epithelial defect area,sub-epithelial nerve fiber density,corneal sensitivity,rh NGF contents in resident AM and corneas were measured after the surgery.RESULTS:rh NGF was sustained release from the AM within 14 d in vitro,with the positive correlation with initial immersion concentration.The immersion of AM in 500μg/mL rh NGF for 30 min achieved the most stable release within 14 d.After transplantation in rabbit cornea,a high concentration of rh NGF in resident rh NGF-AM and cornea was maintained within 8 d.Corneal epithelial healing,nerve fiber regeneration and the recovery of corneal sensitivity were significantly accelerated after the rh NGF-AM transplantation when compared to simple AM transplantation(all P<0.05).CONCLUSION:Simple immersion of AM achieves the sustained release of rh NGF,and promotes corneal epithelial wound healing and nerve regeneration,as well as the recovery of corneal sensitivity in rabbit.

Effect of Water-Soluble Drug Ionization on the Properties of Emulsion Electrospun Polycaprolactone Nanofibers

Core-shell drug-loaded nanofibers were investigated to reduce adverse effects of drugs and achieve stable storage and also to release drugs continuously. In this study,ultrafine polycaprolactone( PCL) fibers were obtained by emulsion electrospinning and the resulting fiber diameters were in the range of 219-475 nm. The fiber diameter,diameter distribution and its release behaviors varied depending on the type and concentration of the added drug solution.Study demonstrated that conductivity of the drug solution was a major parameter that affected the properties of the drug-loaded nanofibers.

Effect of rhBMP-2 sustained-release nanocapsules on the ectopic osteogenesis process in Sprague-Dawley rats

Objective:To explore the effect of sustained-release recombinant human bone morphogenetic protein-2(rhBMP-2) on ectopic osteogenesis in the muscle pouches of rats through preparing rhBMP-2 sustained-release capsules by wrapping morphogenesis protein bones-2(BMP-2)using chitosan nanoparticles,and compositing collagen materials.Methods:Twenty four SpragueDawley rats were randomly divided into four groups with six rats in each group,that is Group A(control group),Group B(only treated with collagen),Group C(rhBMP-2+collagen treated group) and Group D(rhBMP-2/cs+collagen treated group).The composite materials for each group were implanted in the bilateral peroneal muscle pouches in rats.The peroneal muscles were only separated without implanting any materials in control group.Rats were sacrificed 2 weeks and 4 weeks post treatment and samples were cut off for general observation,Micro CT scans and histological observation.Results:General observation showed no new bone formation in Groups A and B mice,while new bones were formed in Groups C and D mice.Two weeks after treatment Micro CT scans showed that The bone volume fraction(BVF),trabecular thickness(Tb. Th),bone mineral density(BMD) in Group C mice were all higher than that in Group D(P<0.05). At the fourth week,the BVK,Tb.Th and BMD were significantly higher than that at the second week(P<0.01).Conclusions:The slow-release effect of rhBMP-2/cs sustained-release capsules can significantly promote ectopic osteogenesis.Its bone formation effect is better than that of rhBMP-2 burst-release group.

Enhancing the dissolution of phenylbutazone using Syloid based mesoporous silicas for oral equine applications

Three mesoporous silica excipients （Syloid~ silicas AL-1 FR XDP 3050 and XDP 3150） were formulated with a model drug known for its poor aqueous solubility, namely phenylbutazone, in an attempt to enhance the extent and rate of drug dissolution. Although other forms of mesoporous silica have been investigated in previous studies, the effect of inclusion with these specific Syloid silica based excipients and more interestingly, with phenylbutazone, is unknown. This work reports a significant enhancement for both the extent and rate of drug release for all three forms of Syloid silica at a 1：1 drug：silica ratio over a period of 30 min. An explanation for this increase was determined to be conversion to the amorphous form and an enhanced drug loading ability within the pores. Differences between the release profiles of the three silicas were concluded to be a consequence of the physicochemical differences between the three forms. Overall, this study confirms that Syloid silica based excipients can be used to enhance dissolution, and potentially therefore bioavailability, for compounds with poor aqueous solubility such as phenylbutazone. In addition, it has been confirmed that drug release can be carefully tailored based on the choice of Syloid~ silica and desired release profile.

Dissipative Particle Dynamics Study on Aggregation of MPEG- PAE-PLA Block Polymer Micelles Loading Doxorubicine

To guide the molecular design of the pH-sensitive triblock amphiphilic polymer MPEG-PAE-PLA and the for- mula design of its doxorubicine （DOX）-loaded micelles, dissipative particle dynamics （DPD） simulations are em- ployed to investigate the aggregation behaviors of the DOX-loaded micelles. The simulation results showed that the aggregate morphologies of micelles and DOX distribution are influenced by degree of polymerization of blocks, and the proposed structure of polymer is MPEG44-PAE3-PLA4. With different contents of polymer or DOX, differ- ent aggregate morphologies of the micelles, like microsphere, spindle/column, reticulation or lamella are observed. To prepare the micro-spherical DOX-loaded micelles, the polymer content is proposed as 10%--15%, and the DOX content less than 10%.