PLGA包埋硫酸庆大霉素缓释微球的制备及体外释放行为

以生物可降解乙交酯和丙交酯的无规共聚物(PLGA)为载体,将硫酸庆大霉素分散在PLGA的有机溶液中,采用复乳溶剂挥发法制备了药物缓释微球。研究搅拌速度、PLGA浓度、乳化剂浓度和硫酸庆大霉素溶液体积对微球粒径的影响,观察微球的表面形貌,测定微球粒径、粒径分布和包封率,评价载药微球的体外释放行为。结果表明,采用甲基纤维素为乳化剂制备的微球形态完整,中粒径为(130±30)μm,微球中硫酸庆大霉素的包封率均在36%以上,平均42%,最高达56%。硫酸庆大霉素/PLGA微球具有显著的药物缓释作用,体外释放30d的累积释药率达80%以上。     

硫酸庆大霉素/壳聚糖纳米球的制备及其释药性能

目的 制备具有预防和降低硫酸庆大霉素耳毒性的壳聚糖纳米球.方法 采用离子交联法,以三聚磷酸钠为离子交联剂,制备了硫酸庆大霉素/壳聚糖纳米球,用透射电子显微镜,X-射线衍射仪和紫外分光光度计考察了其理化性质和释药性能.结果 纳米球的粒径为50～80nm,载药包封率为39.8%,载药量为18.3%,体外60h释药90%左右,释放过程符合双相动力学方程.结论 这可能预示硫酸庆大霉素/壳聚糖纳米球缓释效果可降低硫酸庆大霉素的耳毒性.     

庆大霉素聚氰基丙烯酸丁酯毫微球冻干注射剂的制备及其特性

用乳化聚合法制备庆大霉素聚氰基丙烯酸丁酯毫微球，经冷冻干燥制成冻干型注射剂。用一阶导数分光光度法测定药物的结合率和载药量；以浊度作为评价冻干毫微球重分散性能的指标，筛选配方和工艺；用透射电镜测定了冻干前后粒度分布的变化；对体外释药进行了考察；还对毫微球的其他理化特性进行了测定。     

PLA/CoFe_2O_4载药微球的制备、表征及释药性能

采用 乳化-溶剂挥发法制备了聚乳酸(polylactie acid,PLA)载硫酸庆大霉素复合微球.通过正交设计实验优选PLA载药微球的最佳实验条件.在此基础上利用微乳法制备的铁酸钴(CoFe2O4)制备了PLA/CoFe_2O_4载硫酸庆大霉素复合微球.通过透射电子显微镜(TEM)、X-射线衍射(XRD)、振动样品磁强计(VSM)对铁酸钴进行微观结构表征和性能分析.采用傅立叶变换红外光谱(FT-IR),扫描电子显微镜(SEM)、生物数码显微镜对聚乳酸载药微球和PLA/CoFe_2O_4载药微球进行了微观结构的表征和分析.结果 表明两种载药微球呈规则球形,表面光滑,分布较均匀,平均粒径约为20μm.通过体外模拟释药试验考查了PLA载药微球和PLA/CoFe_2O_4载药微球的释药性能.结果 表明聚乳酸作为药物载体具有明显的药缓控释作用,PLA/CoFe_2O_4载药微球药物释放持续的时间最长.     

用毫微球增加体外小鼠腹腔巨噬细胞与大鼠肝细胞对庆大霉素的摄取

用³H-庆大霉素制备了聚氰基丙烯酸正丁酯毫微球。结果表明,毫微球可使小鼠腹腔巨噬细胞的cpm达³H-庆大霉素溶液对照组的6.34倍,使大鼠肝细胞的cpm在1,12和24h分别达到³H-庆大霉素溶液对照组的27.74,9.03和8.36倍。毫微球的粒径、使用的稳定剂种类、表面活性剂包裹以及庆大霉素的投药量等对摄取量均有明显影响。本研究为筛选细胞内给药系统提供了依据。     

多肽,蛋白质药物的微球给药系统研究进展

本文综述了近年来生物大分子药物微球给药系统的现状，包括长效注射剂，鼻腔、口服给药微球、毫微球的研究进展，探讨了各剂型的释药机理，特点和存在的问题。     

魔芋葡甘聚糖-海藻酸钠载药凝胶微球释药研究

目的:考察不同制备条件对魔芋葡甘聚糖-海藻酸钠载药凝胶微球释药的影响,并对其释药机制进行初步研究。方法:采用滴制法制备凝胶微球,建立体外分析方法,考察多糖浓度、复配比例、加药量对微球释放的影响,绘制释药曲线,并对其进行释药方程拟合,分析释药机理。结果:微球的释药速率随着多糖总浓度、海藻酸钠比例的增大而增加,加药量较小时,释药速率较快,完全释放所需时间较短。释药曲线与一级动力学方程拟合度最高。结论:采用滴制法制备凝胶微球,方法简便易操作,2 h内可基本释放完全,释放机制可用一级动力学方程进行评价。     

甲睾酮聚乳酸微球的制备及其释药性能研究

目的制备甲睾酮聚乳酸微球,研究其体外释药过程。方法采用乳化-溶剂挥发法制备甲睾酮聚乳酸微球;以0.25%SDS-5%乙醇(pH3.4)为释放介质,采用高效液相色谱法测定甲睾酮聚乳酸微球的体外释药量。结果甲睾酮聚乳酸微球开始释药较快,存在一定突释效应,随后以缓慢的方式释药,可用双相动力学方程100-R=35.77e0.1321t+63.91e7.372E-4t描述。结论制成的甲睾酮聚乳酸微球具有明显的缓释作用。     

制备工艺对石杉碱甲微球体外释药机制的影响

目的考察制备工艺对石杉碱甲(Hup)乳酸-羟基乙酸共聚物(PLGA)微球体外释药机制的影响。方法 采用两种O/O型乳化溶剂挥发法工艺(A法和B法)制备Hup微球。考察微球的体外释药曲线，结合微球在释放介质中的降解速度和溶胀速度曲线以及微球的形态和微球中药物的分布情况阐述微球的释药机制。结果采用A法制备的微球包封率为47.60%，体外无明显突释现象，可缓释35 d，符合零级动力学方程，通过扩散和降解两种机制释药。采用B法制备的微球包封率为83.50%，体外可缓释21 d，整体释药曲线符合Higuchi方程，主要以扩散机制释药。结论采用A法制备的微球具有更理想的缓释效果。     

乳酸环丙沙星淀粉微球的体外释药研究

目的：制备乳酸环丙沙星淀粉微球并对其体外释放行为进行考察。方法：采用反相乳液聚合法结合包埋载药法制备乳酸环丙沙星淀粉微球，应用体外恒温透析法考察其释药行为及影响因素，以紫外可见分光光度法测定并计算累积释药百分数。使用origin软件，将微球释药数据与载药微粒的主要释药方程进行拟合，以找出最佳拟合释药方程。结果：制备的乳酸环丙沙星淀粉微球置于生理盐水中约5小时后达到释放平衡，其释放行为受处方中球-药比和交联剂用量及释放介质的影响。该载药淀粉微球的释药行为最符合双指数双相动力学方程，即呈双相释放，前期为快速释放相，后期（5小时后）为缓慢释放相。结论：本制剂工艺切实可行，所得乳酸环丙沙星淀粉微球具有明显的缓释制剂特征。     

Self-Assembled Biodegradable Nanoparticles Developed by Direct Dialysis for the Delivery of Paclitaxel

Purpose The main objective of this study was to obtain self-assembled biodegradable nanoparticles by a direct dialysis method for the delivery of anticancer drug. The in vitro cellular particle uptake and cytotoxicity to C6 glioma cell line were investigated. Methods Self-assembled anticancer drugs—paclitaxel-loaded poly(d,l-lactic-co-glycolic acid) (PLGA) and poly(l-lactic acid) (PLA) nanoparticles—were achieved by direct dialysis. The physical and chemical properties of nanoparticles were characterized by various state-of-the-art techniques. The encapsulation efficiency and in vitro release profile were measured by high-performance liquid chromatography. Particle cellular uptake was studied using confocal microscopy, microplate reader, and flow cytometry. In addition, the cytotoxicity of this drug delivery system was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay on C6 glioma cell line to predict the possible dose response of paclitaxel-loaded PLGA and PLA nanoparticles. Results PLGA and PLA nanoparticles with or without vitamin E tocopherol polyethylene glycol succinate (TPGS) as an additive were obtained, in which the sustained release of paclitaxel of more than 20 days was achieved. The coumarin6-loaded PLGA and PLA nanoparticles could penetrate the C6 glioma cell membrane and be internalized. The cytotoxicity of paclitaxel-loaded nanoparticles seemed to be higher than that of commercial Taxol? after 3 days incubation when paclitaxel concentrations were 10 and 20 μg/ml. Conclusions Direct dialysis could be employed to achieve paclitaxel-loaded PLGA and PLA nanoparticles, which could be internalized by C6 glioma cells and enhance the cytotoxicity of paclitaxel because of its penetration to the cytoplasm and sustained release property.     

The use of response surface methodology for the formulation and optimization of salbutamol sulfate hydrophilic matrix sustained release tablets

The objective of this study was to develop a hydrophilic matrix formulation with in vitro release characteristics similar to Asthalin^® tablets and that would sustain the release of salbutamol sulfate over a 12-h period. A central composite design was used as the framework for manufacturing formulations that may be used to understand the relationships between polymer levels and in vitro release characteristics. Tablets were manufactured using wet granulation with Surelease^® as the granulating fluid and different levels of Methocel^® K100M, xanthan gum, and Carbopol^® 974P as matrix-forming materials. In vitro dissolution testing was conducted using USP Apparatus 3 and samples were analyzed using a validated reversed-phase HPLC method. The results revealed that the levels and types of polymers had a significant impact on the rate of drug release from these formulations and that it was possible to optimize the levels of matrix-forming polymers to achieve the desired release characteristics. Statistical design and response surface methodology have been successfully used to understand and optimize formulation factors and interactions that impact the in vitro release characteristics of salbutamol sulfate from a potential multisource sustained release dosage form.     

Novel polymeric nanoparticles containing tanshinone IIA for the treatment of hepatoma

Novel polylactic acid nanoparticles containing tanshinone IIA (TS-PLA-NPs) were synthesized by a single oil-in-water emulsion/solvent evaporation method. In this study, the optimized nanoparticles were characterized for morphology, mean particle size, zeta potential, entrapment efficiency, drug-loading content, X-ray diffractometer measurement, and in vitro release. The obtained nanoparticles were spherical and intact. The mean particle size was 192.5 nm with polydispersity index being 0.029 and zeta potential ? 26.27 mV. The mean entrapment efficiency and loading of tanshinone IIA (TSIIA) in TS-PLA-NPs were 86.35 and 1.61%, respectively. The in vitro release study was performed at pH 7.4 using a dialysis membrane. Without initial burst effect, the TSIIA sustained release from TS-PLA-NPs for more than 7 days. The mean in vitro cumulative release percentage of TSIIA from TS-PLA-NPs vs. time curve fitted well with the Higuchi Equation (Q = 2.0365 + 13.564 × t_1/2, r = 0.9950). In pharmacokinetics and tissue distribution studies, the concentrations of TSIIA are higher in hepatoma and lower in blood, heart, kidney, spleen, and lung at 2 h after TS-PLA-NPs was administered via caudal vein. TS-PLA-NPs were effective in destroying the human liver cancer cells by the Mono-nuclear cell direct cytotoxicity assay (MTT) assay, and the growth-inhibitory effect of TS-PLA-NPs on human liver cancer cells was concentration and time dependent. The effect of TS-PLA-NPs on hepatoma in mice was also performed. The results of TS-PLA-NPs were markedly more effective than both of TSIIA and blank PLA nanoparticles in preventing tumor growth and increasing survival time of mice with hepatoma. This study provided support for the new paradigm, the application of TSIIA for the treatment of hepatoma.     

Formulation,characterization and pharmacokinetic evaluation of gentamicin sulphate loaded albumin microspheres

The aim of this investigation was to prepare and evaluate microsphere formulations of gentamicin using bovine serum albumin (BSA) as a polymer matrix and glutaraldehyde as a cross-linker. Microsphere formulations of gentamicin were prepared using a spray dryer and were evaluated for product yield, encapsulation efficiency, particle size and in vitro drug release. The anti-microbial testing was performed using a modified Kirby-Bauer technique which showed that encapsulated gentamicin had an equivalent anti-microbial activity against E. coli bacteria as compared to gentamicin solution. Since it was the goal to deliver a high drug load intra-cellularly, the formulation with the least burst release profile in PBS was evaluated for its pharmacokinetic performance in rats. The in vivo pharmacokinetic evaluation on rats demonstrated increased bioavailability with microsphere formulation in comparison to the traditional solution form. The significant increase in bioavailability shall enable one to reduce the frequency of gentamicin administration and would effectively reduce the dose related side effects of gentamicin such as ototoxicity and nephrotoxicity.     

香菇多糖–番荔素纳米粒的性能考察及其对小鼠黑色素瘤肺转移癌的抑制作用

目的 考察香菇多糖–番荔素纳米粒的性能,及其对小鼠黑色素瘤肺转移癌的体内外抑制效果。方法 采用反溶剂沉淀法制备香菇多糖–番荔素纳米粒,以动态光散射法测定粒径、分散系数（PDI）及Zeta电位,及其在不同生理介质（5%的葡萄糖、生理盐水、PBS的混悬液）中的稳定性;采用透射电子显微镜观察纳米粒的形态、大小;精确称量香菇多糖–番荔素纳米粒质量,并采用HPLC法测量番荔素中番荔辛,计算载药量;用酶标仪在540 nm处测量不同浓度（2、1.5、1、0.5、0.25、0.125 mg/mL）香菇多糖–番荔素纳米粒与5%葡萄糖溶液等渗液的吸光度,并计算溶血率;采用透析袋法考察香菇多糖–番荔素纳米粒的体外释放行为。用划痕实验与MTT实验对香菇多糖–番荔素纳米粒进行体外药效学考察。构建黑色素瘤肺转移癌小鼠模型,以紫杉醇注射液为阳性对照,对不同剂量香菇多糖–番荔素纳米粒进行体内药效学研究。结果 香菇多糖–番荔素纳米粒的粒径为（160.6±1.0）nm,PDI为0.082±0.023,Zeta电位为（-28.10±1.14）m V,透射电镜下呈球状。香菇多糖–番荔素纳米粒在5%的葡萄糖、血浆中稳定,无溶血...     

Mannose 6‐phosphate‐modified bovine serum albumin nanoparticles for controlled and targeted delivery of sodium ferulate for treatment of hepatic fibrosis

Objectives The aim was to prepare neoglycoprotein‐based nanoparticles for targeted drug delivery to hepatic stellate cells, and to evaluate their characteristics in vitro and in vivo. Methods The neoglycoprotein of bovine serum albumin modified with mannose 6‐phosphate was synthesised from mannose, and used as wall material to nanoencapsulate the model natural antifibrotic substance sodium ferulate using a desolvation method. The morphology, drug loading capacity, release in vitro and biodistribution in vivo of the nanoparticles were studied. Selectivity of the nanoparticles for hepatic stellate cells was evaluated by immunohistochemical analysis of fibrotic rat liver sections. Key findings The spherical nanoparticles were negatively charged with zeta potential ranging from ?2.73 to ?35.85 mV, and sizes between 100 and 200 nm with a narrow size distribution. Drug entrapment efficiency of about 90% (w/w) and loading capacity of 20% (w/w) could be achieved. In vitro, the nanoparticles showed an initial rapid continuous release followed by a slower sustained release. After intravenous injection into mice, the nanoparticles showed a slower elimination rate and a much higher drug concentration in liver compared with the sodium ferrate solution, and less distribution to the kidneys and other tissues. Immunohistochemistry indicated that the neoglycoprotein‐based nano‐particles were taken up specifically by hepatic stellate cells. Conclusions The nanoparticles may be an efficient drug carrier targeting hepatic stellate cells.     

Biodegradable micro- and nanoparticles as long-term delivery vehicles for gentamicin

Micro- and nanoparticles of poly(lactide-co-glycolide) (PLGA) loading gentamicin were prepared by a solvent evaporation method with the aim of obtaining appropriate vectors for systemic administration. Microspheres presented mean diameters below 3?µm and nanoparticles showed homogeneous sizes with a diameter of 320?nm. Drug loading was more efficient in the case of microencapsulation. The more hydrophilic copolymers with carboxyl-end groups yielded higher microparticle loadings, reaching encapsulation efficiencies up to 9.2?µg?mg^?1 of polymer (502H, 503H or 75:25H). Nanoparticles made of 502H PLGA also achieved an acceptable level of encapsulation (6.2?µg?mg^?1). Particles prepared by using the solvent evaporation method showed no aggregation after hydration, in contrast to the microparticles prepared by spray-drying which showed fast and high auto-aggregation. In vitro release profiles revealed that 503H microspheres showed the highest burst during the first hour, while the most sustained release was for microparticles of 502H copolymer (40% of gentamicin remained in the formulation after 28 days). In summary, microspheres made of 502H, 503H and 75:25H and nanoparticles of 502H showed the best potential properties for systemic use in the treatment of intra-cellular gentamicin-susceptible pathogens.     

Self-assembled nanoparticles of reduction-sensitive poly (lactic-co-glycolic acid)-conjugated chondroitin sulfate A for doxorubicin delivery: preparation,characterization and evaluation

In this study, reduction-sensitive self-assembled polymer nanoparticles based on poly (lactic-co-glycolic acid) (PLGA) and chondroitin sulfate A (CSA) were developed and characterized. PLGA was conjugated with CSA via a disulfide linkage (PLGA-ss-CSA). The critical micelle concentration (CMC) of PLGA-ss-CSA conjugate is 3.5?µg/mL. The anticancer drug doxorubicin (DOX) was chosen as a model drug, and was effectively encapsulated into the nanoparticles (PLGA-ss-CSA/DOX) with high loading efficiency of 15.1%. The cumulative release of DOX from reduction-sensitive nanoparticles was only 34.8% over 96?h in phosphate buffered saline (PBS, pH 7.4). However, in the presence of 20?mM glutathione-containing PBS environment, DOX release was notably accelerated and almost complete from the reduction-sensitive nanoparticles up to 96?h. Moreover, efficient intracellular DOX release of PLGA-ss-CSA/DOX nanoparticles was confirmed by CLSM assay in A549 cells. In vitro cytotoxicity study showed that the half inhibitory concentrations of PLGA-ss-CSA/DOX nanoparticles and free DOX against A549 cells were 1.141 and 1.825?µg/mL, respectively. Therefore, PLGA-ss-CSA/DOX nanoparticles enhanced the cytotoxicity of DOX in vitro. These results suggested that PLGA-ss-CSA nanoparticles could be a promising carrier for drug delivery.     

Mucoadhesive polyethylenimine–dextran sulfate nanoparticles containing Punica granatum peel extract as a novel sustained-release antimicrobial

Abstract

Mucoadhesive polyethylenimine–dextran sulfate nanoparticles (PDNPs) were developed for local oral mucosa delivery. Punica granatum peel extract (PGE) was loaded into PDNPs for oral malodor reduction and caries prevention. PDNPs were constructed using the polyelectrolyte complexation technique employing oppositely charged polymers polyethylenimine (PEI) and dextran sulfate (DS), with PEG 400 as a stabilizer. Under optimal conditions, spherical particles of ～500?nm with a zeta potential of ～+28?mV were produced. Up to 98%, drug entrapment efficiency was observed. The mass ratio of PEI:DS played a significant role in controlling particle size and entrapment efficacy. PDNPs shown to be a good mucoadhesive drug delivery system as confirmed by ex vivo wash off test. In vitro dissolution studies revealed that PGE-loaded PDNPs manifested a prolong release characteristic with a burst release within 5?min. In addition, they remained effectively against oral bacteria.     

Tumor-preferential sustained drug release enhances antitumor activity of block copolymer micelles

Abstract

Nanoparticles are widely used as drug carriers for controlled, tumor-targeted delivery of various anticancer agents that have biopharmaceutical limitations such as water solubility and tissue permeability. Growing evidence suggests that nanoparticles not only reduce toxic side effects of anticancer drugs but also improve the therapeutic efficacy as a function of their drug-release profile. The purpose of this study is to confirm such hypothetical effects of tunable drug release on improving antitumor activity of nanoparticles in vitro and in vivo, using block copolymer micelles as drug carriers. Micelles were prepared from poly(ethylene glycol)-poly(aspartate) block copolymers modified with hydrazide (HYD), aminobenzoate hydrazide (ABZ) and glycine hydrazide (GLY) linkers to achieve a pH-dependent, tunable release of doxorubicin (DOX), a model anticancer drug. Regardless of the drug-release profile, all three micelles showed similar properties in vitro, such as pH-dependent drug release, intracellular drug delivery and cancer cell growth inhibition. However, micelles releasing DOX slowly in vitro showed that the most effective antitumor activity in vivo, compared to the micelles releasing drugs faster. These results demonstrate that tumor-preferential sustained drug release can enhance the antitumor activity of the micelles.