乳酸/羟基乙酸共聚物的分子量及其单体组成比例对利培酮微球性质的影响

目的:制备利培酮-乳酸(LA)/羟基乙酸(GA)共聚物(R-PLGA)缓释微球,并对微球的性质及释放效果进行评价。方法:采用单乳溶剂蒸发法制备R-PLGA缓释微球;对微球的粒径分布、载药量、包封率、突释、体外释放等指标进行测定,考察PL-GA不同分子量和LA/GA不同单体组成比例对微球性质的影响。结果:所制微球外观圆整,分散良好。PLGA的单体组成比例以及分子量对微球性质尤其是释放速度有明显的影响。结论:可通过调节PLGA的分子量和LA/GA单体组成比例改变微球性质,以达到控制微球释放速率等预期目的。     

乳酸/羟基乙酸共聚物分子量对艾塞那肽微球性质的影响

目的:制备艾塞那肽一乳酸/羟基乙酸共聚物(PLGA)微球,并研究PLGA分子量对微球性质的影响.方法:选用不同分子量的PLGA,采用复乳法制备艾塞那肽PLGA微球;对微球的粒径、载药量、包封率和体外释放等指标进行测定.结果:PLGA分子量对艾塞那肽PLGA微球的性质有明显影响.结论:可通过调节PLGA分子量调控微球的性质.     

替莫唑胺乳酸-羟基乙酸共聚物微球的制备及表征

采用乳化-溶剂挥发法制备替莫唑胺微球,考察了制备工艺中影响微球粒径、载药量和包封率的主要因素,筛选处方工艺.按优化工艺制得的微球形态圆整,表面光滑,平均粒径62.2μm,载药量7.5%,包封率83.5%,体外试验表明该载药微球有明显的缓释效果.     

注射用乳酸-羟基乙酸共聚物微球的体内外相关性研究进展

注射用乳酸-羟基乙酸共聚物(polylactide-polyglycolide, PLGA)微球作为一种储库型释药系统,自1989年第1个产品Lupron depot获准在美国上市起,已成功用于多种疾病的治疗,具备在体内几天到几个月长时间释药的能力,可显著改善用药安全性,提升患者顺应性。体内外相关性(in vitro-in vivo correlation, IVIVC)研究给微球制剂的发展带来更多可能。IVIVC可以通过微球的体外释放行为阐述体内释药的动态信息,在表征微球性能的同时减轻各阶段的工作量,对药物的研发、生产变更和监督管理等具有指导或支持作用。本文将注射用PLGA微球的释放机制、体内外释放测定涉及的常用方法和理论进行归纳总结,重点讨论了IVIVC尤其是A级IVIVC在微球制剂领域的建立及应用,为进一步的微球体内外相关性研究提供参考。     

卡铂-乳酸/羟基乙酸共聚物微囊在家兔体内的药动学

目的 :考察卡铂 乳酸 /羟基乙酸共聚物微囊在家兔体内的药动学过程。方法 :健康家兔 8只 ,随机交叉试验 ,单剂量注射卡铂微囊混悬液和卡铂原料药溶液后 ,采用等离子体原子发射光谱法测定血药浓度 ,药 时数据经PKS计算机程序拟合 ,自动判别最佳模型及计算药动学参数。结果 :两种剂型的的药 时曲线符合三室模型 ,二者的药动学参数Cmax、t1/ 2 β、MRT、AUC、CL差异存在显著性 (P <0 .0 5 )。结论 :卡铂制成微囊后 ,在家兔体内具有明显的缓释作用 ,有效作用时间延长 ,有利于其抗肿瘤作用     

乳酸-羟基乙酸共聚物微球的研究进展

通过整理和归纳国内外文献,介绍乳酸-羟基乙酸(PLGA)载药微球的制备方法和作为药物载体的应用。     

罗哌卡因乳酸羟基乙酸共聚物微球的制备及体外释药研究

目的:优化罗哌卡因乳酸羟基乙酸共聚物微球制备工艺,并考察其粉粒学特征和体外释药特性。方法:以乳酸羟基乙酸共聚物为载体,采用W/O/W乳剂-扩散溶剂挥发法制备微球,以微球的粒径、药物包封率、载药量及微球形态等重要粉粒学特征为考察指标,通过正交分析试验优化微球制备工艺,并进行体外释药研究。结果:以优化处方制备的制剂,外观光滑圆整,平均粒径为(2.525±0.047)μm,粒径在1.8～5.0μm的占总数的80%以上,载药量(6.067±0.312)%,包封率(58.05±1.169)%。其体外释药曲线可用Higuchi方程拟合,192h累积释药率达82%,t1/2=60.16h。结论:罗哌卡因乳酸羟基乙酸共聚物微球具有明显的缓释性。     

蛋白质/多肽药物聚乳酸/乳酸-羟基乙酸共聚物微球研究进展

缓释微粒给药系统是蛋白质/多肽药物传输系统的一个重要研究方向，聚乳酸和乳酸-羟基乙酸共聚物是制备缓释微球最常用的载体材料。蛋白质/多肽药物聚乳酸/乳酸-羟基乙酸共聚物微球常用的制备方法包括溶剂萃取/挥发法(复乳法)、相分离法和喷雾干燥法。本文总结了微球制备中面临的难点如蛋白质/多肽药物稳定性、包封率、药物突释和药物吸附等问题，并综述了保持药物结构稳定性和生物活性、提高包封率、改善药物释放曲线等微球制备方法和进展。     

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。     

The pharmacokinetics of recombinant human interferon-alpha-2b poly(lactic-co-glycolic acid) microspheres in rats

Interferon-alpha2b (IFN α-2b) microspheres were prepared at various concentrations (5%, 10%, 15%, 20% and 25%) and viscosities (0.39, 0.6, 0.89 and 1.13?dL/g) of poly(lactic-co-glycolic acid) (PLGA) using double emulsion solvent evaporation. The optimal formulation of IFN α-2b microspheres was determined to be 0.89?dL/g PLGA, as assessed by the in vitro release test. The pharmacokinetics of IFN α-2b microspheres was investigated. Nine groups of rats were injected intramuscularly with three doses (0.5, 1 and 2?MIU) of commercial lyophilized IFNα-2b injection or IFN α-2b microspheres. At a dose of 0.5?MIU, the IFN α-2b microsphere released significantly longer than that of the IFN α-2b injection. At a dose of 2?MIU, each pharmacokinetics parameter of microspheres prepared with the IFNa-2b stock solution was manifestly greater than those of the injection. Our study indicated that the IFN α-2b microspheres prepared in 15% of 0.89?dL/g PLGA provided a sustained drug effect for up to 21 days in rats.     

紫杉醇PLGA微球制备及体外性质评估

目的：以乳酸-羟基乙酸共聚物（PLGA）为材料,制备用于肿瘤内注射的紫杉醇PLGA长效缓释微球.方法：采用改良溶剂蒸发法制备,对微球的体外性质以及不同剂量（10,15,25 kGy）60Coγ射线对微球性质的影响进行考察.结果：制得的微球形态圆整,载药量、包封率、平均粒径和跨距分别为1.53%,97.29%,42.72μm和0.95.药物体外释放30 d累计释放达到56.19%,体外降解30 d后微球失去完整结构,表面粗糙.3个剂量60Coγ射线的灭菌效果均良好,且对微球的体外性质均无明显影响.微球中二氯甲烷的残留量低于药典规定的限度.结论：紫舷杉醇PLGA微球满足缓释长效的要求,对恶性肿瘤的间质化疗具有一定前景.     

Preparation and testing of cefquinome-loaded poly lactic-co-glycolic acid microspheres for lung targeting

The aim of this study was to prepare cefquinome-loaded poly lactic-co-glycolic acid (PLGA) microspheres and to evaluate their in vitro and in vivo characteristics. Microspheres were prepared using a spry drier and were characterized in terms of morphology, size, drug-loading coefficient, encapsulation ratio and in vitro release. The prepared microspheres were spherical with smooth surfaces and uniform size (12.4?±?1.2?μm). The encapsulation efficiency and drug loading of cefquinome was 91.6?±?2.6 and 18.3?±?1.3%, respectively. In vitro release of cefquinome from the microspheres was sustained for 36?h. In vivo studies identified the lung as the target tissue and the region of maximum cefquinome release. A partial lung inflammation was observed but disappeared spontaneously as the microspheres were removed through in vivo decay. The sustained cefquinome release from the microspheres revealed its applicability as a drug delivery system that minimized exposure to healthy tissues while increasing the accumulation of therapeutic drug at the target site. These results indicated that the spray-drying method of loading cefquinome into PLGA microspheres is a straightforward method for lung targeting in animals.     

效应面法优化盐酸昂丹司琼微球的制备工艺

目的：优化盐酸昂丹司琼聚乳酸乙醇酸嵌段共聚物（PLGA）微球的处方工艺。方法：o／o型乳化溶剂挥发法制备微球，采用小复合设计安排实验，考察盐酸昂丹司琼和PLGA的重量比（X1）、PLGA在内相中的浓度（X2）以及正己烷加入的时间（X3）对微球性质的影响。微球性质的评价指标是包封率（Y1）、载药量（Y2）、粒径（Y3）、体外释曲曲线零级方程拟合的相关系数（Y4）和16d的累积释放度（Y5）。根据最佳数学模型绘制效应面图，通过效应面法优化制备工艺。结果：最优工艺：X1为1：10，X2为32％，X3为65min。按照优化工艺制备的微球的包封率为50．69％，载药量4．6l％，粒径为58μm，体外释药曲线符合零级释放（r=0．99），16d的累积释放度约为91％。优化工艺的预测值和实洲值比较接近。结论：采用效应面法完成了盐酸昂丹司琼微球的多目标优化。     

Pharmacokinetic and pharmacodynamic profiles of recombinant human erythropoietin-loaded poly(lactic-co-glycolic acid) microspheres in rats

Aim:

To characterize the pharmacokinetic and pharmacodynamic profiles of the recombinant human erythropoietin (rhEPO)-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres in rats.

Methods:

The rhEPO-loaded microspheres were prepared using a solid-in-oil-in-water emulsion method. Pharmacokinetics and pharmacodynamics of the rhEPO-loaded microspheres were evaluated in male Sprague-Dawley rats. The serum rhEPO level was determined with ELISA. The level of anti-rhEPO antibody in the serum was measured to assess the immunogenicity of rhEPO released from the microspheres.

Results:

rhEPO was almost completely released from the PLGA microspheres in vitro, following zero-order release kinetics over approximately 30 d. After intramuscular injection (10 000 or 30 000 IU rhEPO/kg) in the rats, the serum rhEPO concentration reached maximum levels on d 1, then decreased gradually and was maintained at nearly steady levels for approximately 4 weeks. Furthermore, the release of rhEPO from the PLGA microspheres was found to be controlled mainly by a dissolution/diffusion mechanism. A good linear correlation (R²=0.98) was obtained between the in vitro and in vivo release data. A single intramuscular injection of the rhEPO-loaded PLGA microspheres (10 000 or 30 000 IU rhEPO/kg) in the rats resulted in elevated hemoglobin and red blood cell concentrations for more than 28 d. Moreover, the immunogenicity of rhEPO released from the PLGA microspheres was comparable with that of the unencapsulated rhEPO.

Conclusion:

The results prove the feasibility of using the PLGA-based microspheres to deliver rhEPO for approximately 1 month.     

不同封端的PLGA/PLA-醋酸曲普瑞林微球的制备及体内外评价

目的考察微球载体材料聚乳酸-羟基乙酸共聚物(poly-lactic-co-glycolic acid,PLGA)和聚乳酸(poly(D,L-lactide acid),PLA)的不同封端基团对于包载醋酸曲普瑞林(triptorelin acetate,TA)微球的形态、粒径、包封率、体外释放行为以及体内药效学的影响。方法使用复乳化-溶剂挥发法制备包载TA的PLGA和PLA微球;用扫描电镜观察微球的形态,用激光粒度测定仪测定微球的粒径;建立高效液相色谱法(HPLC)用于TA包封率及体外释放度的测定;采用酶联-免疫吸附法考察了微球经肌肉注射后对正常雄性Sprague Dawley大鼠血浆睾酮浓度的影响。结果制备得到的微球形态为球形或类球形,平均粒径约为30μm。PLGA和PLA,尤其是PLGA,其分子末端基团对TA的包封率和体外释放速率均有影响。酯封端的PLGA微球的包封率显著高于酸封端的微球,而酯封端的释放速度要慢于酸封端。体内药效学实验结果显示,大鼠体内睾酮水平在注射微球后两个小时达到峰值,之后逐渐下降,不同微球之间无显著性差异。结论不同封端结尾的PLGA和PLA对微球形态、包封率和体外释药速率有显著影响,但对正常大鼠体内睾酮水平的影响没有显著性差异。     

聚乳酸乙醇酸在微球控释制剂中的研究进展

聚乳酸乙醇酸(PLGA)是生物可降解的聚合物,已取得了美国FDA的批准,用于组织工程支架和药物载体。由于其具有良好的生物相容性和生物可降解性,近20年来成为小分子药物、蛋白质和其他大分子(DNA、RNA或多肽类)化合物的缓释控释制剂研究的热点。对于PLGA微球制剂的研究主要集中在疫苗类、激素类、抗生素类、抗肿瘤类、神经营养物质类等药物控释制剂。主要介绍近5年来这些药物微球的研究情况,为进一步开发利用PLGA作为药物载体提供参考。     

水溶性添加剂对聚乳酸-聚乙烯醇酸共聚物基质释药动力学的影响

目的选择不同亲水性及空间构型的添加剂，研究其对聚乳酸-聚乙烯醇酸共聚物(poly lactic-co-glycolic acid, PLGA)药物释放动力学的影响，为心血管药物局部用药控释制剂的研究提供理论依据。方法用抗细胞增生药物2-氨基色酮(U-86)作为代表性药物，用溶剂浇铸和压膜结合的方法制备药物/PLGA/添加剂双层膜，在37 ℃磷酸缓冲液中测定体外药物释放并用扫描电镜观察表面形态。结果水溶性添加剂明显地提高了U-86的释放率，并转变为近似的单阶段模式。药物释放速率与基质的失重速率非常吻合。水溶性添加剂的基质在水中形成高度多孔的结构。结论添加剂的水溶性、分子量大小及空间构型等对于聚合物基质的孔隙结构具有决定性作用，而这些孔隙结构的特征又影响着药物释放机制以及释放动力学模式。     

In vitro characteristics of poly（lactic-co-glycolic acid） microspheres incorporating gelatin particles loading basic fibroblast growth factor

AIM: To construct a sustained drug release system for basic fibroblast growth factor (bFGF). With this special system, bFGF can be used to repair an injured peripheral nerve, injured spinal cord, or as a carrier for other drugs that need to be released over a long time. METHODS: Microsphere composite was prepared by encapsulating bFGF into gelatin particles with poly(lactic-co-glycolic acid) (PLGA) as its outer-coating. The encapsulation was conducted by a phase separation method. RESULTS: The average diameter of the gelatin particle-PLGA microsphere composite was 5-18 mum, and bFGF-loading efficiency was up to 80.5%. The bFGF releasing experiment indicated that this new composite system could release bFGF continuously and protect bFGF from denaturation. CONCLUSION: A modified approach was successfully employed to develop a biodegradable system for sustained release of the drug of bFGF in vitro.