The drug encapsulation efficiency, in vitro drug release, cellular uptake and cytotoxicity of paclitaxel-loaded poly(lactide)-tocopheryl polyethylene glycol succinate nanoparticles

Paclitaxel is one of the most effective antineoplastic drugs. Its current clinical administration is formulated in Cremophor EL, which causes serious side effects. Nanoparticle (NP) technology may provide a solution for such poisonous adjuvant problems and promote a sustained chemotherapy, in which biodegradable polymers play a key role. Our group has successfully synthesized novel poly(lactide)-tocopheryl polyethylene glycol succinate (TPGS) (PLA-TPGS) copolymers of desired hydrophobic-hydrophilic balance for NP formulation of anticancer drugs. The present work is focused on effects of the PLA:TPGS composition ratio on drug encapsulation efficiency, in vitro drug release, in vitro cellular uptake and viability of the PLA-TPGS NP formulation of paclitaxel. The PLA-TPGS copolymers of various PLA:TPGS ratios were synthesized by the ring-opening polymerization method and characterized by GPC and (1)H NMR for their molecular structure. Paclitaxel-loaded PLA-TPGS NPs were prepared by a modified solvent extraction/evaporation method and characterized by laser light scattering for size and size distribution, scanning electron microscopy for surface morphology and zeta potential for surface charge. High performance liquid chromatography was used to measure the drug encapsulation efficiency and in vitro drug release profile. Cancer cell lines HT-29 and Caco-2 were used to image and measure the cellular uptake of fluorescent PLA-TPGS NPs. Cancer cell viability of the drug-loaded PLA-TPGS was measured by MTT assay. It was found that the PLA:TPGS composition ratio has little effects on the particle size and size distribution. However, the PLA-TPGS NPs of 89:11 PLA:TPGS ratio achieved the best effects on the drug encapsulation efficiency, the cellular uptake and the cancer cell mortality of the drug-loaded PLA-TPGS NPs. This research was also carried out in close comparison with the drug-loaded PLGA NPs.     

Long-term animal implantation study of biotube-autologous small-caliber vascular graft fabricated by in-body tissue architecture

This study aimed to synthesize and characterize biodegradable microcapsules based on poly(lactic acid) (PLA) and ethylcellulose (EC) for a controlled delivery of calcium hydroxide. Phase separation technique was adopted to synthesize calcium hydroxide-loaded PLA/EC microcapsules. Four PLA/EC blends (4/1, 1/1, 1/4, pure EC) were used as shell materials and the input ratio of calcium hydroxide to shell polymer was 4:1 for all microcapsules. The morphology and composition were studied using SEM-EDS and TEM. Particle size distribution, glass-transition temperature, drug loading, and encapsulation efficiency were characterized. In vitro release of the microcapsules was evaluated using a pH microelectrode and an auto-biochemistry analyzer. SEM images of microcapsules showed uniform spherical structures with smooth surfaces. Core-shell, hetero-structures were confirmed using TEM. The presence of calcium in the microcapsules was verified with EDS. Pure calcium hydroxide was 160 nm in diameter and the particle size of the microcapsules ranged between 500 nm and 4 μm. With an increase of PLA in PLA/EC blend, the size of microcapsules increased accordingly. Encapsulation efficiency of these microcapsules was higher than 57% and drug loading was higher than 80%, which were not significantly different among four microcapsules. Pure calcium hydroxide powder was used as a control and 90% was released within 48 h, while release of calcium hydroxide from microcapsules took between 168 and 456 h, depending on the PLA/EC ratio. Compared with calcium hydroxide powder, the calcium hydroxide-loaded microcapsules showed a sustained and prolonged release, which could be controlled via the regulation of the PLA/EC ratio.     

Poly(lactide)–vitamin E derivative/montmorillonite nanoparticle formulations for the oral delivery of Docetaxel

Four systems of nanoparticles of biodegradable polymers were developed in this research for oral delivery of anticancer drugs with Docetaxel used as a model drug, which include the poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs), the poly(lactide)–vitamin E TPGS nanoparticles (PLA–TPGS NPs), the poly(lactic-co-glycolic acid)–montmorillonite nanoparticles (PLGA/MMT NPs) and the poly(lactide)–vitamin E TPGS/montmorillonite nanoparticles (PLA–TPGS/MMT NPs). Vitamin E TPGS stands for d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), which is a water-soluble derivative of natural vitamin E formed by esterification of vitamin E succinate with polyethylene glycol (PEG) 1000. The design was made to take advantages of TPGS in nanoparticle technology such as high emulsification effects and high drug encapsulation efficiency, and those in drug formulation such as high cellular adhesion and adsorption. MMT of similar effects is also a detoxifier, which may cure some side effects caused by the formulated drug. The drug-loaded NPs were prepared by a modified solvent extraction/evaporation method and then characterized for their MMT content, size and size distribution, surface charge and morphology, physical status and encapsulation efficiency of the drug in the NPs, and in vitro drug release profile. Cellular uptake of the coumarin 6-loaded NPs was investigated. In vitro cancer cell viability experiment showed that judged by IC₅₀, the PLA–TPGS/MMT NP formulation was found 2.89, 3.98, 2.12-fold more effective and the PLA–TPGS NP formulation could be 1.774, 2.58, 1.58-fold more effective than the Taxotere^® after 24, 48, 72 h treatment, respectively. In vivo PK experiment with SD rats showed that oral administration of the PLA–TPGS/MMT NP formulation and the PLA–TPGS NP formulation could achieve 26.4 and 20.6 times longer half-life respectively than i.v. administration of Taxotere^® at the same 10 mg/kg dose. One dose oral administration of the NP formulations could realize almost 3 week sustained chemotherapy in comparison of 22 h of i.v. administration of Taxotere^®. The oral bioavailability can be enhanced from 3.59% for Taxotere^® to 78% for the PLA–TPGS/MMT NP formulation and 91% for the PLA–TPGS NP formulation respectively. Oral chemotherapy by nanoparticles of biodegradable polymers is feasible.     

聚乳酸/聚乙二醇琥珀酸酯-姜黄素纳米粒的制备及体外评价*

背景：聚乳酸及其共聚物是一类具有良好生物相容性的可降解高分子材料,已被广泛用于可生物降解型药物缓释或靶向给药系统中。 目的：探索载药纳米粒制备条件对包封率和载药量的影响,确定最佳制备工艺条件。 方法：以维生素E1000聚乙二醇琥珀酸酯(TPGS)为乳化剂、姜黄素为模型药物、聚乳酸为载体材料,采用O/W型乳化-溶剂挥发法制备聚乳酸-姜黄素纳米粒,以包封率和载药量为主要指标,单因素实验探索影响两指标的主要因素,再正交试验设计优化制备工艺。 结果与结论：通过正交试验设计制备聚乳酸-姜黄素纳米粒的最佳工艺为：水油相比10∶1,聚合物浓度15 g/L,药物浓度3 g/L,乳化剂TPGS浓度0.03%。以此工艺制备的载药纳米粒外形圆整光滑,粒度分布较为均匀,平均粒径为167.5 nm,包封率为89.52%,载药量为13.72%,纳米粒前期突释不明显具有良好的缓释作用。该工艺稳定、简单可行,优化制备工艺得到的聚乳酸-姜黄素纳米粒粒径适中、包封率和载药量较高。     

Cationic core–shell nanoparticles with carmustine contained within O-benzylguanine shell for glioma therapy

The application of carmustine (BCNU) for glioma treatment is limited due to its poor selectivity for tumor and tumor resistance caused by O⁶-methylguanine-DNA-methyl transferase (MGMT). To improve the efficacy of BCNU, we constructed chitosan surface-modified poly (lactide-co-glycolides) nanoparticles (PLGA/CS NPs) for targeting glioma, loading BCNU along with O⁶-benzylguanine (BG), which could directly deplete MGMT. With core–shell structure, PLGA/CS NPs in the diameter around 177 nm showed positive zeta potential. In vitro plasma stability of BCNU in NPs was improved compared with free BCNU. The cellular uptake of NPs increased with surface modification of CS and decreasing particle size. The cytotoxicity of BCNU against glioblastoma cells was enhanced after being encapsulated into NPs; furthermore, with the co-encapsulation of BCNU and BG into NPs, BCNU + BG PLGA/CS NPs showed the strongest inhibiting ability. Compared to free drugs, PLGA/CS NPs could prolong circulation time and enhance accumulation in tumor and brain. Among all treatment groups, F98 glioma-bearing rats treated with BCNU + BG PLGA/CS NPs showed the longest survival time and the smallest tumor size. The studies suggested that the co-encapsulation of BCNU and BG into PLGA/CS NPs could remarkably enhance the efficacy of BCNU, accompanied with greater convenience for therapy.     

紫杉醇纳米粒子制备及血管内局部灌注后的组织分布

目的 制备紫杉醇纳米粒子,并考察其在实验兔体内经DispatchTM球囊灌注后组织分布情况.方法 以生物可降解材料聚乳酸聚乙醇酸共聚物(PLGA)为原料,采用超声乳化-溶剂挥发法制备载紫杉醇纳米粒子.对纳米粒子的粒径、形态、药物含量和体内外释放进行测定.通过新西兰兔腹主动脉局部给药模型考察紫杉醇纳米粒子球囊灌注后组织分布情况.结果 制备的紫杉醇纳米粒子的平均粒径约为246 nm,包封率为93.25％,紫杉醇含量19.06％.体外可维持恒定释放30d以上.新西兰兔体内经腹主动脉实现DispatchTM球囊灌注,观察药物可在靶部位体内贮留长达21d.结论 紫杉醇PLGA纳米粒子作为一种局部药物传递系统,经球囊灌注在动物模型体内提高局部药物浓度,延长药物作用时间,可实现缓释靶向治疗.     

Novel protein-loaded chondroitin sulfate-chitosan nanoparticles: preparation and characterization

In this study, the potential of chondroitin sulfate (ChS)–chitosan (CS) nanoparticles (NPs) for the delivery of proteins was investigated. ChS–CS NPs were prepared by ionic cross-linking of CS solution with ChS. The aggregation line, particle size and zeta potential were investigated as a function of the pH, weight ratio and concentration. The water content and formation yield of the NPs were measured by gravimetry. Results indicated that ChS–CS NPs showed a higher degree of ionic cross-linking and formation yield than sodium tripolyphosphate–CS NPs. Fluorescein isothiocyanate conjugate bovine serum albumin (FITC–BSA), a model protein drug, was incorporated into the ChS–CS NPs. The encapsulation efficiency was obviously increased with the increase in initial FITC–BSA concentration and was as high as 90%. In vitro release studies of ChS–CS NPs showed a small burst effect following a continued and controlled release. Cytotoxicity tests with Caco-2 cells showed no toxic effects of ChS–CS NPs. The ex vivo cellular uptake studies using Caco-2 and HEK-293 cells indicated that NPs were found to be endocytosed into the cells. In conclusion, ChS–CS NPs are a potential new delivery system for the transport of hydrophilic compounds such as proteins.     

Co-delivery of chemotherapeutic drugs with vitamin E TPGS by porous PLGA nanoparticles for enhanced chemotherapy against multi-drug resistance

We report a strategy to make use of poly(lactic-co-glycolic acid) nanoparticle (PLGA NPs) for co-delivery of docetaxel (DTX) as a model anticancer drug together with vitamin E TPGS. The latter plays a dual role as a pore-forming agent in the nanoparticles that may result in smaller particle size, higher drug encapsulation efficiency and faster drug release, and also as a bioactive agent that could inhibit P-glycoprotein to overcome multi-drug resistance of the cancer cells, The DTX-loaded PLGA NPs of 0, 10, 20 and 40% TPGS were prepared by the nanoprecipitation method and then characterized for their size and size distribution, surface morphology, physical status and encapsulation efficiency of the drug in the NPs. All four NPs were found of size ranged 100–120 nm and EE ranged 85–95% at drug loading level around 10%. The in vitro evaluation showed that the 48 h IC₅₀ values of the free DTX and the DTX-loaded PLGA NPs of 0, 10, 20% TPGS were 2.619 and 0.474, 0.040, 0.009 μg/mL respectively, which means that the PLGA NPs formulation could be 5.57 fold effective than the free DTX and that the DTX-loaded PLGA NPs of 10 or 20% TPGS further be 11.85 and 52.7 fold effective than the DTX-loaded PLGA NPs of no TPGS (therefore, 66.0 and 284 fold effective than the free DTX). Xenograft tumor model and immunohistological staining analysis further confirmed the advantages of the strategy of co-delivery of anticancer drugs with TPGS by PLGA NPs.     

Optimization of 5-flurouracil solid-lipid nanoparticles: a preliminary study to treat colon cancer

Solid lipid nanoparticle (SLNs) formulae were utilized for the release of 5-flurouracil (5-FU) inside the colonic medium for local treatment of colon cancer. SLNs were prepared by double emulsion-solvent evaporation technique (w/o/w) using triglyceride esters, Dynasan™ 114 or Dynasan™ 118 along with soyalecithin as the lipid parts. Different formulation parameters; including type of Dynasan, soyalicithin:Dynasan ratio, drug:total lipid ratio, and polyvinyl alcohol (PVA) concentration were studied with respect to particle size and drug entrapment efficiency. Results showed that formula 8 (F8) with composition of 20% 5-FU, 27% Dynasan™ 114, and 53% soyalithicin and F14 (20% 5-FU, 27% Dynasan™ 118, and 53% soyalithicin), which were stabilized by 0.5% PVA, as well as F10 with similar composition as F8 but stabilized by 2% PVA were considered the optimum formulae as they combined small particle sizes and relatively high encapsulation efficiencies. F8 had a particle size of 402.5 nm ± 34.5 with a polydispersity value of 0.005 and an encapsulation efficiency of 51%, F10 had a 617.3 nm ± 54.3 particle size with 0.005 polydispersity value and 49.1% encapsulation efficiency, whereas formula F14 showed a particle size of 343 nm ± 29 with 0.005 polydispersity, and an encapsulation efficiency of 59.09%. DSC and FTIR results suggested the existence of the lipids in the solid crystalline state. Incomplete biphasic prolonged release profile of the drug from The three formulae was observed in phosphate buffer pH 6.8 as well as simulated colonic medium containing rat caecal contents. A burst release with magnitudes of 26%, 32% and 28.8% cumulative drug released were noticed in the first hour samples incubated in phosphate buffer pH 6.8 for both F8, F10 and F14, respectively, followed by a slow release profile reaching 50%, 46.3% and 52% after 48 hours.     

骨碎补总黄酮/聚乳酸-羟基乙酸微囊的制备

背景：微囊是目前靶向治疗给药体系的主要方向之一,其大小为数微米到数百微米,可用于口服、注射、动脉给药及局部靶器官治疗等多种治疗途径。目的：制备骨碎补总黄酮/聚乳酸-羟基乙酸共聚物微囊,并对微囊制备条件进行优化。方法：采用乳化溶剂挥发法制备骨碎补总黄酮/聚乳酸-羟基乙酸共聚物微囊,单因素分析聚乳酸-羟基乙酸共聚物质量浓度(60,100,140,180 g/L)、搅拌速度(50,1 000,2 000,4 000 r/min)、初乳乳化时间(2,4,6,8 min)及水油比(1∶5、1∶10、1∶15、1∶20)对微囊大体形态、粒径分布宽度与微囊中总黄酮包封率的影响,筛选出微囊粒径较小、分散均匀、包封率较高的骨碎补总黄酮/聚乳酸-羟基乙酸共聚物微囊。结果与结论：确定最佳工艺参数为：140 g/L 聚乳酸-羟基乙酸共聚物溶液,匀浆机2 000 r/min搅拌速度,初乳乳化时间6 min,水油比为1∶15。优化工艺下所制备的微囊分布均匀,平均粒径为(789.8±712.3) nm,粒径分布宽度较窄,基本小于5 μm;扫描电镜下观察所见微囊呈圆形,边缘较规则;微囊平均包封率为47.72%。  中国组织工程研究杂志出版内容重点：人工关节;骨植入物;脊柱;骨折;内固定;数字化骨科;组织工程     

膜乳化法制备单分散性载羟基喜树碱缓释微球

目的 研究利用微孔膜乳化法制备载抗癌药10-羟基喜树碱（IqCPT）缓释微球的可行性。方法 以HCPT为模型药物,聚乳酸（PEA）为载体,以膜乳化法制备载药微球,并研究制剂的表面形态、载药率、包封率和缓释效果等性质。结果 膜乳化法制备的载HCPT聚乳酸微球,粒径可控制在1-10μm之间。表面圆整,稳定性、单分散性良好,载药率和包封率最高分别可达32．7％和81．7％,24h体外累积释放量为17．3％。结论 膜乳化法制备的载HCPT微球制剂均匀分散,具有明显缓释效果,是制备缓释微球制剂的较好方法。     

Nanoparticles of poly(lactide)-tocopheryl polyethylene glycol succinate (PLA-TPGS) copolymers for protein drug delivery

Nanoparticles (NPs) of poly(lactide)-tocopheryl polyethylene glycol succinate (PLA-TPGS) copolymers with various PLA:TPGS component ratios were prepared by the double emulsion technique for protein drug formulation with bovine serum albumin (BSA) as a model protein. Influence of the PLA:TPGS component ratio and the BSA loading level on the drug encapsulation efficiency (EE) and in vitro drug release behavior was investigated. The PLA-TPGS NPs achieved 16.7% protein drug loading and 75.6% EE, which exhibited a biphasic pattern of controlled protein release with higher initial burst for those NPs of more TPGS content. Furthermore, the released proteins retained good structural integrity for at least 35 days at 37 degrees C as indicated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and circular dichroism (CD) spectroscopy. Compared with other biodegradable polymeric NPs such as poly(D,L-lactide-co-glycolide) (PLGA) NPs, PLA-TPGS NPs could provide the encapsulated proteins a milder environment. Confocal laser scanning microscopy (CLSM) observation demonstrated the intracellular uptake of the PLA-TPGS NPs by NIH-3T3 fibroblast cells and Caco-2 cancer cells. This research suggests that PLA-TPGS NPs could be of great potential for clinical formulation of proteins and peptides.     

乳酸-羟基乙酸共聚物载药纳米粒的制备及体外释药性

背景：医用纳米粒作为药物传递的新型载体,目前已经成为医药领域研究的重点。 目的：构建以生物可降解材料乳酸-羟基乙酸共聚物为载体,负载抗肿瘤药物5-氟尿嘧啶的载药纳米粒。 方法：利用复乳-溶剂挥发法制备乳酸-羟基乙酸共聚物载药纳米粒。场发射扫描电子显微镜观察纳米粒表面形态;激光粒度分析仪测定粒径分布并计算成球率;紫外分光光度计测定5-氟尿嘧啶载药量、包封率,并对体外释药进行评估。 结果与结论：纳米粒呈球性,平均粒径为(186±14) nm,成球率、载药量和包封率分别为70.8%、6.6%、28.1%,体外释药有突释现象,24 h内5-氟尿嘧啶累积释药量达36.2%,10 d达83.6%。提示成功制备乳酸-羟基乙酸共聚物载药纳米粒,其具有缓释效应。     

In vitro and in vivo evaluation of methoxy polyethylene glycol-polylactide (MPEG-PLA) nanoparticles for small-molecule drug chemotherapy

Methoxy polyethylene glycol-polylactide (MPEG-PLA) nanoparticles (NPs) were prepared by the nanoprecipitation method with particle size of 140+/-21nm in diameter and drug encapsulation efficiency of 87.6+/-3.1%. In vitro cytotoxicity of the drug formulated in the NPs was investigated with MCF-7 cancer cells in close comparison with that of Taxol((R)). The in vitro cytotoxicity with MCF-7 cells showed that the NP formulation could be 33.3, 10.7, 7.7 times more effective than Taxol((R)) after 24, 48, 72h culture at the same drug concentration of 1microg/ml. Confocal laser scanning microscopy (CLSM) visualized cellular internalization of the coumarin 6-loaded MPEG-PLA NPs. The in vitro results were further confirmed by the in vivo pharmacokinetic analysis with SD rats. The total area-under-the-curve (AUC(0-infinity)), which determines the therapeutic effects of a dose, was found to be 29,600+/-1,690ng-h/ml for the NP formulation, which is 3.09 times of 9,570+/-1,480ng-h/l for Taxol((R)) with 10mg/kg dose i.v. injection. The half-life (t(1/2)) of the drug formulated in the NPs was found to be 18.80+/-3.14h, which is 2.75 times of 6.84+/-1.39h for Taxol((R)). The distribution volume at steady state for the drug loaded in the NPs was 7.21+/-2.17l/kg, which was 2.93 times of 2.46+/-1.41l/kg for Taxol((R)). Our proof-of-concept in vitro and in vivo valuation shows that our MPEG-PLA NP formulation could have great advantages versus the original drug in small-molecule drug chemotherapy as well as in various applications in nanomedicine.     

In vitro evaluation of antisense oligonucleotide functionalized core-shell nanoparticles loaded with α-tocopherol succinate

Antisense oligonucleotide (ASO)-conjugated-α-tocopherol succinate (TCS)-loaded-poly(lactic acid)-g-poly(ethylene glycol) nanoparticles (ASO-TCS-PLA-PEG NPs), with the ratio of polymer/TCS of 10:2.5, 10:5, 10:7 (w/w) were prepared for targeting cancer therapy. The amphiphilic PLA, amino terminated PEG graft copolymers were synthesized by ring opening polymerization reaction. Nanoparticles were produced by using double emulsion (w/o/w) solvent evaporation method. ASO-TCS-PLA-PEG NPs demonstrated satisfactory encapsulation and loading efficiency and size distribution. The short-term stability studies were carried out at 4 and 25 °C for 30 days to assess their mean particle size, polydispersity index and zeta potential. The cellular uptake and extended cytoplasmic retention of the NPs in A549 human lung carcinoma and L929 mouse fibroblast cells were examined by fluorescence and confocal microscopy. In human lung cancer cells, ASO-TCS-PLA-PEG NPs exhibited better cellular internalization, cytotoxicity and apoptotic and necrotic effects compared to healthy cell line, L929. These findings showed that ASO-modified nanoparticles could serve as a promising nanocarrier for targeted tumor cells.     

载表柔比星的壳聚糖纳米粒的制备及其特性研究

目的 制备经聚乙二醇修饰的壳聚糖纳米粒(PEG/CS NP),并负载表柔比星(EPI),研究载表柔比星的壳聚糖纳米粒(PEG/CS-EPI NP)体外释药性能.方法 应用阴离子凝聚法制备PEG/CS-EPI NP,透射电镜观察纳米粒的形态特征,激光粒度分析仪测定粒径大小,紫外分光光度法测定纳米粒的载EPI量,动态透析法考察载EPI纳米粒的体外释放特性.结果 当壳聚糖与三聚磷酸钠质量比为6∶1,壳聚糖与EPI质量比为8∶1时,制备的PEG/CS-EPI NP呈圆形或椭圆形,分散性良好,平均粒径(322.1±14.4)nm,载EPI量为(13.9±1.1)%,包封率(74.2±1.8)%,72 h累积释药率达(82.0±2.1)%.结论 采用阴离子凝聚法制备的PEG/CS-EPI NP形状规则、粒度分布均匀,具有较高包封率和较好缓释性能.     

Comparison of ciprofloxacin hydrochloride-loaded protein, lipid, and chitosan nanoparticles for drug delivery

The aim of the present study was to develop single dose delivery systems based on nanotechnology for prolonged antibiotic release in a controlled manner. Five different drug-carrier ratios of ciprofloxacin hydrochloride-loaded nanoparticles of albumin, gelatin, chitosan (CS), and lipid [solid lipid nanoparticles (SLNs)] were prepared and characterized. Average particle size was found to be in the range of 73 +/- 2 to 98 +/- 44 nm for SLNs, 140 +/- 7 to 175 +/- 24 nm for albumin nanoparticles, 143 +/- 18 to 184 +/- 27 nm for gelatin nanoparticles, and 247 +/- 48 to 322 +/- 52 nm for CS nanoparticles. A drug-to-carrier ratio of 0.5:1 was preferred for CS nanoparticles having zeta potential of >20 mV and drug encapsulation of 35.01% +/- 2.66%. Similarly, 0.6:1 ratio was preferred for albumin nanoparticles with zeta potential >16 mV and drug encapsulation 48.20% +/- 3.01%. Zeta potentials of gelatin nanoparticles loaded with ciprofloxacin suggested that they were unstable and prone to flocculation. SLN with 0.25:1 drug carrier ratio showed 38.71% +/- 2.38% drug entrapment and -28 +/- 1 mV surface charge. All the nanoparticles showed sustained drug release avoiding "burst effect" of the free drugs for up to 120 h for albumin nanoparticles, 96 h for CS and gelatin nanoparticles, and 80 h for SLNs. The drug release profiles followed Higuchi model. Results suggest that CS nanoparticles and SLNs can act as promising carriers for sustained ciprofloxacin release in infective conditions.     

Biodegradable microparticles and fiber fabrics for sustained delivery of cisplatin to treat C6 glioma in vitro

The duration of cisplatin release from most of the drug delivery devices seemed to be shorter than 14 days except large microparticles. The objective of this study was to fabricate and characterize cisplatin-loaded PLA microparticles, PLA/PLGA (30/70) composite microparticles, and fibers as formulations for long-term sustained delivery of cisplatin to treat C6 glioma in vitro by electrospray and electrospinning techniques. Cisplatin-loaded biodegradable microparticles with particle size of around 5 microm and fiber fabrics with diameter of 0.5-1.7 microm were obtained using electrospray and electrospinning techniques. Encapsulation efficiency and in vitro release of formulations were measured by ICP-OES. The encapsulation efficiency for different samples of microparticles was approximately from 33% to 72% and the fiber fabrics had encapsulation efficiency greater than 90%. Cisplatin-loaded microparticles showed typical characteristics of cisplatin release profile: a large initial burst followed by a sustained slow release of 35 days. The composite PLA/PLGA (30/70) microparticles could reduce the initial burst release of cisplatin because of their core-shell structures. In contrast, more than 75 days sustained release could be achieved by fiber fabric formulations without large initial burst. MTT assay was used to quantify the cytotoxicity of different formulations against C6 glioma cells. Microparticle formulations had slightly higher cytotoxicity than free drug. In contrast, the cytotoxicity of fiber fabrics formulation was around 4 times higher than of the free drug based on the actual amount of drug released. The microparticle and fiber fabric formulations presented may be promising for the sustained delivery of cisplatin to eliminate the undesired side effects caused by direct injection of cisplatin solution in systemic administration.     

Nanoparticles of poly(D,L-lactide)/methoxy poly(ethylene glycol)-poly(D,L-lactide) blends for controlled release of paclitaxel

Paclitaxel is one of the best antineoplastic drugs found in nature in the past decades, which has excellent therapeutic effects against a wide spectrum of cancers. Because of its high hydrophobicity, Cremophor EL has to be used as adjuvant in its clinical dosage form (Taxol), which has been found to cause serious side effects. Nanoparticles of biodegradable polymers may provide an ideal solution. In this research, paclitaxel-loaded nanoparticles of poly(D,L-lactide)/methoxy poly(ethylene glycol)-polylactide (PLA/MPEG-PLA) blends of various blend ratio 100/0, 75/25, 50/50, 25/75, and 0/100 were formulated by the nanoprecipitation method for controlled release of paclitaxel. It was found that increasing the proportion of MPEG-PLA component in the blend from 0 to 100% resulted in a progressive decrease of the particle size from 230.6+/-11.1 nm to 74.8+/-14.0 nm. The zeta potential of the drug-loaded nanoparticles was increased accordingly from -19.60+/-1.13 mV to a nearly neutral, that is, -0.33+/-0.28 mV, which indicates the gradual enrichment of PEG segments on the particle surface. The findings were further confirmed by X-Ray Photoelectron Spectroscopy (XPS) analysis. Differential scanning calorimetry (DSC) analysis showed that the glass transition temperature of PLA was significantly decreased from 58.7 to 52.1 degrees C with an increase of MPEG-PLA proportion from 0 to 75%, suggesting the miscibility of PLA and MPEG-PLA. The pure PLA nanoparticles (100/0) exhibited the slowest drug-release rate with 37.3% encapsulated drug released from the nanoparticles for 14 days while the MPEG-PLA nanoparticles (0/100) achieved the fastest drug release with 95.9% drug release in the same period.     

盐酸表阿霉素纳米靶向制剂的缓释效应

背景：盐酸表阿霉素是一种广谱抗生素,目前临床使用的不足多为药物释放快、目标组织药物浓度低,静脉给药后广泛分布于体内各种组织器官,不良反应明显。 目的：针对盐酸表阿霉素临床应用的不足,制备盐酸表阿霉素纳米靶向注射制剂。 方法：以叶酸偶联牛血清白蛋白为载体,采用乳化-高压匀质法,制备盐酸表阿霉素纳米靶向注射制剂,以激光粒度分析仪测定纳米颗粒的粒径大小、粒径分布及Zeta电位,扫描电镜观察纳米颗粒的表面形态,高效液相色谱法分析白蛋白负载盐酸表阿霉素纳米制剂的包封率、载药量和释药性能。 结果与结论：制备的盐酸表阿霉素纳米粒外观呈均匀球型,粒径分布较窄,平均粒径为(157.73±     0.40) nm,平均 Zeta 电位为(-30.85±0.43) mV,载药量 22.78%,包封率可达96.24%。体外模拟释药结果表明药物释放曲线分为两个阶段,突释阶段微球释药量在24 h内达42.6%,缓释阶段纳米粒释药持续时间长,在112 h 时释药量达 84.1%,载药纳米粒的药物释放速率持续稳定。结果表明乳化结合高压匀质法制备的盐酸表阿霉素纳米靶向制剂粒径均匀,粒径范围分布窄,载药量和包封率高,具有一定的缓释作用。