聚乳酸聚乙醇酸微球体外突释的影响因素的研究

目的 考察几种影响干扰素α-2b聚乳酸聚乙醇酸(PLGA)微球体外释放突释的主要因素.方法 在复乳法的基础上结合海藻酸钠与钙离子螯合形成缓释凝胶的原理制备微球,研究海藻酸钠种类和浓度、PLGA黏度和浓度对微球突释的影响.结果 制备的微球形态圆整,结构致密,平均粒径范围为25～55 μm.微球的突释随着PLGA黏度或浓度...     

白藜芦醇PLGA长效注射微球的制备及工艺考察

目的采用乳化溶剂挥发法制备白藜芦醇聚乳酸羟基乙酸[poly(lactic-co-glycolic acid),PL-GA]长效微球,评价各因素对微球性质的影响。方法以微球的包封率、载药量、突释和粒径作为微球的质量评价指标,研究分散相与连续相的体积比、PLGA浓度、聚乙烯醇(polyvinyl alcohol,PVA)浓度、搅拌速度对微球性质的影响,并优化白藜芦醇PLGA微球的制备工艺。结果分散相与连续相的体积比为1∶50时,包封率高,但4 h突释量达到76%,当分散相与连续相体积比由1∶50提升到1∶150时,突释降低了22%;随着聚合物浓度的增加粒径明显增大,突释显著降低;理论载药量对粒径影响不大,在高载药量时突释显著减少;搅拌速度的增加使粒径减小,突释增加;PVA浓度的增加对粒径没有明显的影响,但当PVA的质量浓度从1 g.L-1增加到5 g.L-1时,包封率从93.57%降低到80.31%。结论分散相与连续相的体积比、PLGA浓度、PVA浓度、搅拌速度对微球性质有很大的影响。优化条件下制备的微球形态完整,载药量为(27.86±1.00)%,包封率为(93.57±2.87)%,平均粒径约为21.12μm。白藜芦醇PLGA微球体外释放25 d的累积释药率达(94.04±4.94)%,有望研制成1个月给药1次的给药系统。     

白益母草总生物碱聚乳酸-羟基乙酸共聚物微球的制备

目的:优化蒙药白益母草总生物碱的聚乳酸-羟基乙酸共聚物(PLGA)微球的处方工艺,制备微球并对其进行质量考察。方法:采用复乳-液中干燥法制备白益母草总生物碱PLGA微球,以处方中PLGA质量浓度、聚乙烯醇(PVA)浓度及内水相/油相体积比为因素,以微球的载药量、包封率、收率的综合评分为指标,采用L9(34)正交试验优化制备微球的处方工艺,并考察微球形态、粒径及体外释药情况。结果:最优工艺为PLGA 200 mg/ml、PVA 2%、内水相/油相的体积比为1∶5;验证试验中平均包封率为(83.2±2.4)%,平均载药量为(4.16±0.17)%,平均收率为(86.7±3.6)%,综合评分结果为(95.7±4.4)%,RSD均小于5.0%(n=3);制备的微球形态圆整,表面光滑,粒径分布均匀,平均粒径为(22.3±2.4)μm;微球24 h体外累积释放度为(82.3±3.5)%,符合一级释放模型(r=0.972 4)。结论:优选工艺稳定;制备的微球具有良好的缓释性能,质量符合要求。     

复乳法制备胰岛素PLGA纳米粒影响包封率因素考察

以Poloxamer188为乳化剂，乙酸乙酯为有机溶剂，采用复乳法制备了胰岛素乳酸／羟基乙酸共聚物（PLGA）纳米粒，考察了乳化剂和PLGA的浓度。内水相中胰岛素的浓度为pH，溶剂挥发方法和内水相中加入聚乙烯醇（PVA）等实验各因素对胰岛素PLGA纳米粒包封率的影响。结果表明，乳化剂的浓度较高，PLGA的浓度较小，内水相的pH接近胰岛素的pI(5．3），胰岛素的浓度较低，缩短有机溶剂挥发时间及内水相中加入PVA有利于提高胰岛素的包封率，经实验条件优化后制备的胰岛素PLGA纳米纳平均粒径为149．6nm，多分散性系数小于0．1，包封率提高到42．8％。     

一种聚乳酸聚乙醇酸缓释微球的制备工艺

目的:研究一种制备聚乳酸聚乙醇酸(PLGA)微球的新工艺,即将海藻酸钠与钙离子螯合形成缓释凝胶的原理与复乳法制备微球的工艺相结合。方法:以牛血清白蛋白(BSA)为模型药,以包封率、载药量、产率作为评价指标,研究PLGA黏度、海藻酸钠浓度及外水相1中氯化钙浓度对微球性质的影响,并通过L9(34)正交试验设计优选微球制备的工艺条件。结果:优选的制备工艺重现性好,微球形态圆整,结构致密,平均粒径为67.5μm,载药量、包封率和产率分别为0.669%、53.38%和80.08%。结论:本研究获得了较为满意的制备PLGA微球的新工艺,微球的理化性质良好。     

盐酸维拉帕米PLGA纳米粒的成型工艺及制剂学性质研究

目的 优化影响盐酸维拉帕米乳酸/羟基乙酸共聚物(PLGA)纳米粒成型工艺的参数,并评价优化工艺后所制纳米粒的制剂学性质.方法 采用O/W超声乳化-溶剂挥发法制备盐酸维拉帕米PLGA纳米粒(VRP-PLGANP),以粒径、包封率和载药量为评价指标,采用单因素试验系统考察PLGA浓度、PLGA/VRP质量比、PVA浓度、有机相中丙酮浓度、外水相pH、内外相(O/W)体积比、探头超声时间、旋蒸时间共8个参数对纳米粒成型工艺的作用规律.结果 用优化处方工艺制备的纳米粒的包封率和载药量分别为65.78%±6.32%和22.75%±1.48%、平均粒径为150.4±6.9 nm、PDI=0.070±0.018(n=3),体外释放规律符合Weibull方程,具有一定的缓释特性.结论 所用方法可用于制备载两亲性药物的PLGA纳米粒.     

改良自乳化-溶剂扩散法制备甲基莲心碱纳米粒的研究

目的制备甲基莲心碱纳米粒(NEF-NP),并采用正交试验设计对甲基莲心碱纳米粒制备工艺进行优化。方法以包封率和载药量为评价指标,采用聚乳酸-羟基乙酸共聚物(PLGA)为载体,丙酮-无水乙醇为有机溶剂,通过正交设计优化改良自乳化-溶剂扩散法制备载NEF的PLGA载药纳米粒的处方工艺。结果优化的最佳处方工艺为:PLGA的浓度为20 mg.mL-1,NEF的投药量为3.3 mg,PVA浓度为1.0%,水相与有机相的体积比为8∶1。最佳条件下制得的纳米粒平均包封率达(70.35±1.16)%,载药量(2.33±1.08)%,平均粒径为(213.5±2.7)nm。结论最佳处方工艺制备的NEF-PLGA纳米粒具有较高的包封率、载药量和较小的粒径。     

沉淀法制备甲基莲心碱聚乳酸-羟基乙酸共聚物纳米粒

目的:制备甲基莲心碱聚乳酸-羟基乙酸共聚物纳米粒(Nef-PLGA-NPs)。方法:以聚乳酸-羟基乙酸共聚物(PLGA)为载体,丙酮为有机溶剂,通过正交试验设计优化沉淀法制备甲基莲心碱PLGA纳米粒的工艺。结果:最佳工艺条件为:PLGA的质量浓度为10 mg.mL-1,Nef的质量浓度为1.0 mg.mL-1,水相与有机相的体积比为20∶1。纳米粒平均包封率为(85.3±0.8)%,平均载药量为(7.75±0.07)%,平均粒径为(82.9±1.2)nm。结论:优化条件下采用沉淀法制备的甲基莲心碱PLGA纳米粒包封率高、载药量大,平均粒径小。     

罗哌卡因-醋酸地塞米松PLGA微球的制备及体外释药特性研究

目的 制备罗哌卡因 醋酸地塞米松聚乳酸羟基乙酸共聚物（PLGA）微球（简称微球）并研究其体外释药特性。方法以PLGA为载体,采用W1/O/W2双重乳化 溶剂挥发法制备微球,研究实验过程中有机相PLGA浓度、外水相/有机相体积比、内水相体积、外水相聚乙烯醇（PVA）浓度几项因素变化对罗哌卡因 醋酸地塞米松PLGA微球粒径、表面形态﹑载药量﹑包封率和突释行为的影响。结果有机相PLGA浓度在制备微球的过程中是一个关键性因素。随着PLGA浓度增加,微球粒径增大,载药量﹑包封率明显提高,突释降低;外水相/有机相体积比增大,微球粒径增大, 载药量﹑包封率明显提高,微球表面更加光滑﹑微孔减少,突释降低;随着内水相体积增加使得微球表面的微孔明显增多,突释增加,载药量﹑包封率降低;当外水相PVA浓度由0.5%增加到2%,微球粒径变小,突释效应增加。通过优化条件制备的微球形状为球形,外观光滑圆整,粒径分布均匀,其中＞90%分布在20～70 μm。罗哌卡因载药量（7.48±0.33）%,包封率（70.97±2.36）%;醋酸地塞米松载药量（1.52±0.16）%,包封率（57.30±1.17）%。结论采用W1/O/W2双重乳化 溶剂挥发法成功制备罗哌卡因加醋酸地塞米松PLGA微球;以优化工艺制备的微球,在体外具有明显的缓释行为,释药曲线呈典型S形三阶段模式。     

细胞膜红色荧光探针PLGA纳米粒的制备及表征

目的以聚乳酸-羟基乙酸共聚物(PLGA)和单甲氧基聚乙二醇聚乳酸-羟基乙酸共聚物(MePEG-PLGA)为材料,制备包载细胞膜红色荧光探针(DiI)的纳米粒,为后续的细胞实验奠定基础。方法采用自乳化溶剂扩散法制备纳米粒;超滤法分离纯化纳米粒,紫外可见分光光度法测定DiI的含量,并计算包封率。结果 DiI用量为0.5 mg,PLGA或MePEG-PLGA投入量为50 mg,PVA浓度为0.5%,可制得粒径较合适的纳米粒。DiI-PLGA-NP平均粒径为(280.7±3.6)nm,Zeta电位为(2.98±0.47)mV,包封率可达88.0%;DiI-MePEG-PLGA-NP平均粒径为(157.2±3.2)nm,Zeta电位为(-4.90±0.54)mV,包封率可达87.1%。结论 DiI作为脂溶性良好的示踪剂,用其制得的荧光素纳米粒可为后续的体外实验奠定良好的基础。     

Preparation and characterization of poly(D,L-lactic-co-glycolic Acid) microspheres containing flurbiprofen sodium

This study aimed to prepare biodegradable microspheres containing flurbiprofen sodium, a nonsteroidal anti-inflammatory drug (NSAID), as the drug delivery system to the periodontal pocket. Microspheres were prepared from biodegradable copolymers of poly (D,L-lactic-co-glycolic acid) (PLGA) using solvent evaporation method. The effects of the different copolymers and amounts of polyvinyl alcohol (PVA) as a dispersing agent on characteristics of the microspheres were evaluated. Although there was no correlation between microsphere size and amount of PVA, an optimum PVA concentration was essential to achieve narrower size distributions of microspheres. As the concentration of PVA increased, the drug loading of the microspheres increased. The effect of PVA on drug loading was found to be statistically significant for those microspheres prepared from PLGA 50:50 (p < 0.05). Regarding copolymer composition, PLGA 85:15 provided higher drug loading into the microspheres than PLGA 50:50 (p < 0.05). The recoveries of microspheres (60-80%) were affected neither by different PVA concentrations nor by copolymer compositions (p > 0.05). According to the first-order release rate constants of the microspheres, the microspheres of PLGA 50:50 released the drug at the highest rate consistently, with the highest hydrophilicity of this copolymer.     

A short-term (accelerated release) approach to evaluate peptide release from PLGA depot formulations

An accelerated method to evaluate peptide release from poly(dl-lactide-co-glycolide) (PLGA) depot formulations in short time is described. Peptide-loaded microspheres were made from hydrophilic 50∶50 PLGA by a dispersionsolyent extraction technique, and peptide release was studied at 37°C and at higher temperatures in various media. For all accelerated conditions, release was faster at temperatures above the glass transition, Tg, of the host polymer. Complete release of peptide from 8600 MW PLGA was achieved in 35 hours at 50°C in buffered and nonbuffered media containing 0.5% polyvinyl alcohol (PVA). Type of release media and concentration of PVA influenced the release profiles. A PVA concentration of 0.1 to 0.5% was found to prevent aggregation of microspheres at higher temperatures, with an increase in release at the higher PVA concentration. Peptide release was associated with a reduction of pH of the releasing media and increased mass loss. Complete peptide release at pH 4 from 8.6 kd and 28 kd PLGA at 50 and 60°C occurred within 30–40 hours and correlated well with the real-time release at 37°C and pH 7.0. At the higher molecular weight, a slightly longer accelerated release time and higher temperature were required to correlate with the real-time release. The data suggest that by optimization of release conditions such as temperature, surfactant concentration, buffer component, and pH, an accelerated study could be employed to evaluate depot formulations for a given polymer type.     

Preparation of poly(DL-lactide-co-glycolide) microspheres encapsulating all-trans retinoic acid

Poly(DL-lactide-co-glycolide) (PLGA) microspheres containing all-trans retinoic acid (atRA) were prepared by o/w solvent evaporation method and various preparation parameters, such as poly(vinyl alcohol) (PVA) concentration in aqueous solution, PVA MW, drug weight, solvent, polymer MW, and polymer weight, on the characteristics of microspheres and drug release were investigated. PVA concentration in water phase was a critical factor in making microspheres consistently with smooth surface and round shape. In our study, at least 2% (w/v) of PVA in aqueous solution was necessary for making microspheres with round shape. The particle size of microspheres ranged 10-100 microm. AtRA was slowly released from PLGA microspheres over 30 days. Sterilization of microspheres by ethylene oxide (EO) gas at 37 degrees C did not significantly affect the characteristics of drug release or its morphology. Cell growth inhibition of atRA was affected by preparation process of microspheres rather than the EO-gas sterilization process. These results indicate that PLGA microspheres containing atRA are acceptable for controlled release devices for use in the treatment of brain tumor.     

β-methasone-containing biodegradable poly(lactide-co-glycolide) acid microspheres for intraarticular injection: effect of formulation parameters on characteristics and in vitro release

A sustained drug release system based on the injectable poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with β-methasone was prepared for localized treatment of rheumatic arthritis. The microscopy and structure of microspheres were characterized by scanning electron microscope (SEM) and Fourier transform infrared (FTIR). The effects of various formulation parameters on the properties of microspheres and in vitro release pattern of β-methasone were also investigated. The results demonstrated that increase in drug/polymer ratio led to increased particle size as well as drug release rate. Increase in PLGA concentration led to increased particle size, but decreased burst release. The drug encapsulation efficiency increased sharply by increasing polyvinyl alcohol (PVA) concentration in the aqueous phase from 1.5 to 2.0%. β-methasone release rate decreased considerately with decreasing OP (organic phase)/AP (aqueous phase) volume ratio. Stirring rate had significantly influence on the particle size and encapsulation efficiency. Independent of formulation parameters, β-methasone was slowly released from the PLGA microspheres over 11 days. The drug release profile of high drug loaded microspheres agree with Higuchi equation with a release mechanism of diffusion and erosion, that of middle drug loaded microspheres best agreed with Hixcon-Crowell equation and controlled by diffusion and erosion as well. The low drug loaded microspheres well fitted to logarithm normal distribution equation with mechanism of purely Fickian diffusion.     

Insulin-loaded PLGA microspheres for glucose-responsive release

Porous poly(lactic-co-glycolic acid) (PLGA) microspheres were prepared, loaded with insulin, and then coated in poly(vinyl alcohol) (PVA) and a novel boronic acid-containing copolymer [poly(acrylamide phenyl boronic acid-co-N–vinylcaprolactam); p(AAPBA-co-NVCL)]. Multilayer microspheres were generated using a layer-by-layer approach depositing alternating coats of PVA and p(AAPBA-co-NVCL) on the PLGA surface, with the optimal system found to be that with eight alternating layers of each coating. The resultant material comprised spherical particles with a porous PLGA core and the pores covered in the coating layers. Insulin could successfully be loaded into the particles, with loading capacity and encapsulation efficiencies reaching 2.83?±?0.15 and 82.6?±?5.1% respectively, and was found to be present in the amorphous form. The insulin-loaded microspheres could regulate drug release in response to a changing concentration of glucose. In vitro and in vivo toxicology tests demonstrated that they are safe and have high biocompatibility. Using the multilayer microspheres to treat diabetic mice, we found they can effectively control blood sugar levels over at least 18 days, retaining their glucose-sensitive properties during this time. Therefore, the novel multilayer microspheres developed in this work have significant potential as smart drug-delivery systems for the treatment of diabetes.     

Stabilization and encapsulation of a staphylokinase variant (K35R) into poly(lactic-co-glycolic acid) microspheres

The aim of this study is to prepare poly(lactic-co-glycolic acid) (PLGA) microspheres containing a staphylokinase variant K35R (DGR) with purpose of preserving the protein stability during both encapsulation and drug release. DGR-loaded microspheres are fabricated using a double-emulsion solvent extraction technique. Prior to encapsulation, the effect of ultrasonication emulsification of DGR solutions with methylene chloride on protein recovery was investigated. Moderate ultrasonic treatment of aqueous DGR/dichloromethane mixtures caused approximately 84% DGR aggregation. Polyvinyl alcohol (PVA) added into aqueous DGR solutions significantly improved DGR recovery to >90%. The effects of co-encapsulated PVA and NaCl in the external aqueous phase on the characteristics of the microspheres were investigated. When 2% PVA was co-encapsulated and 2.5% NaCl was added to the external water phase, DGR encapsulation efficiency was significantly increased from 7.1% to 78.1% and DGR was distributed uniformly throughout the microspheres. In vitro release test showed that DGR was released from PLGA microspheres in a sustained manner over 15 days. A large amount of released DGR was inactive in the absence of co-encapsulated PVA. On the contrary, when 2% PVA was co-encapsulated, the released DGR was almost completely intact within 9 days. In conclusion, PLGA microspheres can be an effective carrier for DGR and form a promising depot system.     

Formulation and in-vitro characterization of retinoic acid loaded poly (lactic-co-glycolic acid) microspheres

Poly (lactic-co-glycolic acid) (PLGA) microspheres containing all-trans retinoic acid (atRA) were prepared by emulsion/solvent evaporation technique. PLGA (50:50) with inherent viscosities of 0.17 and 0.39 dL g(-1) was used. Polyvinyl alcohol (PVA) or PVA and sodium oleate (SO) combinations (4:1) were used to stabilize the emulsions. The effect of polymer viscosity, emulsifier type and concentration on the in vitro release of atRA from the microspheres was investigated. The stability of the microparticles was also tested at the temperatures of 4, 25 and 40 degrees C. The particle size ranged between 1-2 microm. Microspheres were smooth and spherical in shape, as determined by scanning electron microscope (SEM) photographs. The yield of microspheres ranged from 50-75% and the encapsulation efficiency was determined between 45-75%. In vitro release studies showed that atRA release from microspheres lasted for 11 days.     

A Heterogeneously Structured Composite Based on Poly(lactic-co-glycolic acid) Microspheres and Poly(vinyl alcohol) Hydrogel Nanoparticles for Long-Term Protein Drug Delivery

Purpose. To prepare a heterogeneously structured composite based on poly (lactic-co-glycolic acid) (PLGA) microspheres and poly(vinyl alcohol) (PVA) hydrogel nanoparticles for long-term protein drug delivery. Methods. A heterogeneously structured composite in the form of PLGA microspheres containing PVA nanoparticles was prepared and named as PLGA-PVA composite microspheres. A model protein drug, bovine serum albumin (BSA), was encapsulated in the PVA nanoparticles first. The BSA-containing PVA nanoparticles was then loaded in the PLGA microspheres by using a phase separation method. The protein-containing PLGA-PVA composite microspheres were characterized with regard to morphology, size and size distribution, BSA loading efficiency, in vitroBSA release, and BSA stability. Results. The protein-containing PLGA-PVA composite microspheres possessed spherical shape and nonporous surface. The PLGA-PVA composite microspheres had normal or Gaussian size distribution. The particle size ranged from 71.5 m to 282.7 m. The average diameter of the composite microspheres was 180 m. The PLGA-PVA composite microspheres could release the protein (BSA) for two months. The protein stability study showed that BSA was protected during the composite microsphere preparation and stabilized inside the PLGA-PVA composite microspheres. Conclusions. The protein-containing PLGA-PVA composite may be suitable for long-term protein drug delivery.     

不同PLGA型号对奥曲肽微球的包封率和体外释放行为的影响

考察了不同型号聚乳酸-羟基乙酸共聚物(PLGA)作为水溶性药物奥曲肽微球载体对载药量、包封率和体外释放行为的影响.结果表明,PLGA中丙交酯含量降低,载药量和包封率降低,而突释量增大.PLGA型号相同时,黏度较大的PLGA微球载药量和包封率较高,突释量较小.采用PLGA与聚乳酸(PLA)混合材料制备的微球比单用PLGA材料微球的突释量小、载药量和包封率高、缓释效果好.