PLA对贝美前列素植入剂体外释放行为影响的考察

高眼压是不可逆性眼病的重要原因,但传统滴眼液存在诸多缺点,为了开发长效缓释的眼用植入剂,考察了聚丙交酯(PLA)对贝美前列素植入剂体外释放行为的影响.采用溶剂挥发-热熔挤出的方法制备了长5 mm、直径0.5 mm、载药量20％的贝美前列素-聚乙交酯丙交酯(PLGA)植入剂.通过考察加入不同量PLA的植入剂的体外释放度、...     

丙交酯-乙交酯共聚物中残留单体的去除

将丙交酯-乙交酯共聚物(PLGA)溶于二氯甲烷中,用稀盐酸为萃取剂(即稀酸萃取法)或乙醇为沉淀剂(乙醇沉淀法)去除PLGA中残留的乙交酯和丙交酯单体.考察了两种方法的工艺参数对单体残留量的影响.结果表明,稀酸萃取法比乙醇沉淀法的去除效果好,但所用盐酸会破坏PLGA;沉淀法能有效避免PLGA的降解,且工艺简单.上述两法的去除效果均优于真空加热法.     

乳化分散法制备聚乳酸微球的研究进展

介绍人工合成高分子材料聚乳酸和乙交酯丙交酯共聚物(PLA/PLGA)及PLA/PLGA微球乳化分散制备技术,包括有机溶剂的选择、难溶药物的制备技术、复乳制备技术以及微球表面的乳化剂(PVA)含量的测定方法等.     

乳化分解法制备聚乳酸微球的研究进展

介绍人工合成高分子材料聚乳酸和乙交酯丙交酯共聚物（PLA／PLGA）及PLA／PLGA微球乳化分解制备技术，包括有机溶剂的选择、难溶药物的制备技术、复乳制备技术以及微球表面的乳化剂（PVA）含量的测定方法等。     

以乳酸-羟乙酸共载体的纳米粒给药系统

乳酸 ( lactic acid) 与羟乙酸 (glycolic acid)的共聚物包括两种 : 一种是乳酸 - 羟乙酸共聚物 (poly- lactic acid- co- glycolic acid, 简称 PLGA), 为一定量的乳酸与羟乙酸聚合后的产物 ; 另一种是丙交酯 - 乙交酯共聚物 ( poly(lactide- co- glycoli- de)或 polyglactin 370, 简称 PLGA或 PLGA370) , 其合成原料为 2分子乳酸的脱水物 - 丙交酯和 2分子羟乙酸的脱水物 - 乙交酯 , 两者先在酸性条件下水解成相应的酸 , 再进一步缩合成丙交酯 - 乙交酯共聚物 . 在共聚物中 , 乳酸与羟乙酸的比例或丙交酯与乙交酯的比例可从 50∶ 50改变为 75∶ 25、 85∶ 15, 这种变化不但会影响聚合物的结晶度 , 也会影响聚合物的降解速率 , 进而影响纳米粒的降解以及被包封药物的释放 . PLGA可在体内分解 , 最终生成二氧化碳和水 , 对机体无不良影响 , 因此被视为理想的载体材料且广泛应用于各种药物的纳米粒制剂 .     

PLGA的结构和分子量对纳曲酮微球体外释药的影响

制备了分子量、比旋度、摩尔比及分子链末端修饰不同的丙交酯-乙交酯共聚物,并测定理化参数.以其为载体制备纳曲酮微球,比较了体外释药速率.结果表明,用分子量较小、有光学活性、单体摩尔比较小、分子链末端未酯化的共聚物制备的微球体外释药速率较快.     

作为肽疫苗载体的聚丙交酯-乙交酯微球

作者通过对聚丙交酸-乙交酯(PLG)微球中丙交酯与乙交酯配比的研究以及对影响聚合物降解和内容物释放两项参数的研究,探讨了作为肽疫苗载体的PLG微球在免疫应答中的作用.作者合成了狂犬病病毒ERA株的部分核蛋白:多肽31D带有免疫显性辅助性T细胞表位;多肽V10c含有线性B细胞表位.此外,作者采用3种不同配方制备了3种PLG微球:(1)50/50.2 PLG微球:丙交酯:乙交酯为1:1,分子量为8000Da,微球直径为1～20μm;(2)50/50.74 PLG微球:丙交酯:乙交酯为1:1,分子量为60000Da,微球直径为10～60μm;(3)85/15 PLG微球:丙交酯:乙交酯为85:15,分子量为95000Da,微球直径为50～100μm.分别将31D多肽和31D与V10c多肽的结合物掺入3种PLG微球中制成含肽微球.用酯酶处理微球,用反向高效液相层析测定肽从PLG制剂中的相对释放率.结果显示,50/50.2 PLG制剂在酯     

脂蟾毒配基PLGA-TPGS纳米粒的质量评价

目的：以自制材料乙交酯丙交酯共聚物-维生素E聚乙二醇1000琥珀酸酯（polylactide-co-glycolide-D-α-tocopheryl polyethylene glycol 1000 succinate,PLGA-TPGS）为载体制备脂蟾毒配基PLGA-TPGS纳米粒（Resibufogenin-loaded PLGA-TPGS nanoparticles,RPTN）,并以市售材料乙交酯丙交酯共聚物（PLGA）为载体制备脂蟾毒配基PLGA纳米粒（RBG-loaded PLGA nanoparticles,RPN）,体外评价和比较2种纳米粒的质量。方法：采用超声乳化-溶剂挥发法制备RPTN和RPN,用透射电子显微镜和激光粒度仪分别测定二者的外观、粒径、表面电荷。采用反相高效液相色谱法,色谱柱为Hypersil C₁₈（4.6 mm×250 mm,5 μm）,甲醇和0.05%冰醋酸溶液（9∶1）为流动相,检测波长为298 nm,测定RBG在RPTN和RPN中的载药量、包封率和体外释放度。结果：RPTN和RPN的粒径分别为152.3 nm和331.7 nm,载药量和包封率分别为18.4%、79.3%和15.1%、68.6%。体外药物释放30 d时RPTN和RPN的体外累积释放率分别为86.7%和72.3%,RPTN释放较完全。结论：自制载体制备的RPTN比RPN粒径更小,载药量和包封率更大,体外有明显的缓释作用,释放更完全。     

丙交酯—乙交酯共聚物组成比的不同对微球释药速率的影响

二种组成比不同的丙交酯—乙交酯共聚物以溶剂挥发法制成含炔诺酮的微球。通过体外释药、大鼠注射部位药物残留量的测定及大鼠动情周期抑制试验。证明药物用共聚物PLGA制成微球,能延缓炔诺酮的释放。体内实验显示微球能显著延长大鼠动情周期抑制的时间。且随着共聚物中GA比例的增加,炔诺酮的释药速率加快。     

乙交酯-丙交酯共聚物精制过程中有机锡的去除方法

在乙交酯-丙交酯共聚物(PLGA)精制过程中,比较了采用稀酸溶液和有机溶剂为萃取剂对聚合物中有机锡的去除效果,并考察了以有机溶剂为萃取剂时各工艺参数对精制效果的影响.结果表明,将PLGA溶于乙腈中配成1％的溶液后用等体积石油醚萃取3次,所得产品中锡残留量低于10 μg/g.该法能有效避免酸性条件下PLGA的降解,不使用无机酸.     

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。     

5-Fluorouracil delivery from a novel three-dimensional micro-device: in vitro and in vivo evaluation

A novel three-dimensional biodegradable micro-device using microelectromechanical systems technology was developed for implantable controlled drug delivery. In order to evaluate the effect of monomer composition and molecular weight of poly(lactic-co-glycolic acid) (PLGA) on the drug release, three 5-Fluorouracil loaded micro-devices, made of 50/50, 27 kDa; 50/50, 40 kDa and 75/25 27 kDa PLGA, were prepared and characterized by in vitro and in vivo methods. The in vitro drug release from three micro-devices followed zero-order kinetics, and PLGA micro-device with the higher molecular weight and lactide/glycolide ratio tended to a longer sustained release period. The in vivo release results agreed with the in vitro results and drug release in vivo was faster than that in vitro for each of micro-devices. And three micro-devices showed different tumor inhibition effect in the tumor bearing mice. In addition, the SEM and weight loss experiments showed that PLGA micro-devices with lower molecular weight and lactide/glycolide ratio had faster degradation. These data provided the information for the optimization of the novel three-dimensional biodegradable micro-device to obtain more suitable systems for controlled release and to meet release requirements of different drugs.     

Changes in morphology of in situ forming PLGA implant prepared by different polymer molecular weight and its effect on release behavior

The effects of polymer molecular weight on drug release behavior would be more complicated from in situ forming implants (ISFIs) that change gradually from liquid to semi-solid or solid after injection. To investigate this phenomenon, three commercially available D,L-lactic acid-co-glycolic acid (PLGA) polymers with molecular weights of 12, 34, and 48 kDa were used to prepare ISFIs containing leuprolide acetate (LA) as a model peptide. The influence of polymer molecular weight on the membrane formation, morphology, and also on their in vitro drug release behavior over a period of 28 days was investigated. Results showed that the amount of drug released over the first 24 h (36% +/- 0.34%) (burst release), for formulation prepared with polymer RG 503H (medium molecular weight, M(w) 34 kDa), was significantly higher than others (p < 0.05). Surface and cross-section morphology of ISFI prepared with medium molecular weight polymer to cellular and spongy-like structure which was in good agreement with the release behavior of LA from it.     

聚乳酸-乙醇酸共聚物降解行为对缓控释制剂药物释放行为影响的研究进展

在以聚乳酸–乙醇酸共聚物（PLGA）为辅料的药物缓控释制剂中,药物的释放行为主要取决于PLGA聚合物的降解行为。PLGA的降解行为受骨架结构、环境因素和剂型因素等影响。对PLGA的降解机制进行剖析,并综述影响PLGA降解行为的相关因素,包括PLGA的单体聚乳酸与聚乙醇酸的比例、相对分子质量、pH值、结晶度、温度、药物的类型和基质包封药物后的剂型等,同时论述了其对缓控释制剂药物释放行为的影响。     

Polymer and microsphere blending to alter the release of a peptide from PLGA microspheres.

The objective of this study was to evaluate the effect of polymer and microsphere blending in achieving both a sufficient initial release and a desired continuous release of a peptide from poly(D, L-lactide-co-glycolide) microspheres. Leuprolide acetate loaded hydrophilic 50:50 PLGA microspheres were prepared by a solvent-extraction/evaporation process and were characterized for their drug load, bulk density, size distribution, surface area, surface morphology, in vitro drug release, and in vivo efficacy. Combining PLGA polymers that varied in their molecular weights in various ratios yielded microspheres with varied drug release profiles commensurate with the hydration tendencies of the polymers. Increasing the component of lower molecular weight 50:50 hydrophilic PLGA polymer, 8.6 kDa increased the initial drug release. A similar microsphere formulation prepared instead with blending microspheres from individual polymers showed a similar increase. In an animal model, microspheres obtained from polymer or microsphere blends attained a faster onset of testosterone suppression as compared to microspheres from higher molecular weight 50:50 hydrophilic PLGA polymer, 28.3 kDa, alone. These studies illustrated the feasibility of blending polymers or microspheres of varied characteristics in achieving modified drug release. In particular the increased initial release of the peptide could help avoid the therapeutic lag phase usually observed with microencapsulated macromolecules.     

利培酮长效注射微球的制备及体外释放的研究

目的：制备利培酮长效注射微球并考察其体外释放行为。方法：使用乳酸-羟基乙酸共聚物（PLGA）为材料,采用乳化-溶剂挥发法制备利培酮微球,观察微球的形态及粒径,测定微球的载药量和包封率,考察微球的体外释放情况。结果：利培酮微球表面圆整,粒径集中在40～80μm之间。微球的包封率较高,达到80％以上,以低分子量PLGA（50：50）制备的微球,体外突释很高达到40％以上;以高分子量PLGA（75：25）制备的微球,在高载药量时突释较小,可持续释放达3周以上。结论：以高分子量PLGA制备的高载药量的利培酮微球,体外突释较小可缓释达3周以上。     

Carboplatin-loaded PLGA microspheres for intracerebral injection: formulation and characterization

The purpose of this study is to prepare and characterize injectable carboplatinloaded poly(D,L-lactic-co-glycolic) acid copolymer (PLGA) microspheres for the intracerebral treatment of malignant glioma. The microspheres were prepared by an acetone/mineral oil emulsion and solvent evaporation method. Preparation variables were optimized and the following processing conditions resulted in the highest drug loading and best yields of the microspheres compared with those prepared with the other variables: the PLGA concentration was 8%(w/w) in the internal phase; the emulsifier (Span 80) concentration was 8%(w/w) in the external phase; the ratio of the internal phase: the external phase was 1:8; the stirring speed was 1500 rpm; the emulsion time was 15 min; the solvent evaporation time was 3.75 hr. Microspheres so prepared were analysed for size distribution, drug loading, in vitro release and morphological characteristics. The drug release in phosphate buffer solution started with a 10- day slow release period, followed by a fast near zero order release period from 12 to 22 days. The carboplatin release in brain homogenate was slower than in phosphate buffer solution. The morphological changes of the microspheres during the in vitro degradation correlated with the drug relase profile. In conclusion, the carboplatin-loaded PLGA microspheres were specifically prepared to meet the specification as an injectable and biodegradable brain implant.     

Microspheres made by w/o/o emulsion method with reduced initial burst for long-term delivery of endostar, a novel recombinant human endostatin

The purpose of this work is to design biodegradable Poly(lactide-co-glycolide) (PLGA) microspheres with low initial burst for sustained delivery of Endostar (a novel recombinant human endostatin) and investigate effects of PLGA molecular weight and composition on the release behavior of Endostar microspheres. Endostar microspheres were prepared by using novel w/o/o multiple emulsification-evaporation technique. Effects of polymer molecular weight and copolymer composition on particle properties and release behavior (in vitro and in vivo) have been reported. Drug release in vitro decreased with increase in molecular weight and lactide content of PLGA. Zero order release and low initial burst were obtained with all microsphere formulations. The in vivo performance of Endostar microspheres were also found to be dependent on the polymer molecular weight and copolymer composition. Together, these results suggest that the initial burst release can be reduced by w/o/o emulsion method and the release of Endostar can be changed significantly by varying the polymer molecular weight and copolymer composition.     

罗替戈汀原位形成植入剂的处方研究

目的通过单因素考察优化处方,制备罗替戈汀原位形成植入剂。方法采用聚乳酸-羟基乙酸共聚物(PLGA)为载体,以体外累积释放度为指标考察PLGA类型、PLGA相对分子质量、PLGA质量浓度和载药量对罗替戈汀原位形成植入剂的影响,优化最佳处方。结果罗替戈汀原位形成植入剂的最佳处方为:以PLGA 7525 5A为载体、N-甲基-2-吡咯烷酮为溶剂的PLGA质量浓度为25%、载药量为50%。制备的罗替戈汀原位形成植入剂体外释药30 d累积释放度达85%以上,具明显的缓释特征。结论罗替戈汀原位形成植入剂结合了缓释注射剂和植入剂的优点,体外具有良好的缓释效果。     

Preparation, characterization, and in vitro evaluation of 1- and 4-month controlled release orntide PLA and PLGA microspheres

PURPOSE: To prepare, characterize and evaluate in vitro sustained delivery formulations for a novel LHRH antagonist, Orntide acetate, using biodegradable microspheres (ms). METHODS: Poly(d,l-lactide) (PLA) and poly(d,l-lactide-co-glycolide) (PLGA) were characterized for molecular weight (Mw, Mn) using gel permeation chromatography (GPC) and content of free end carboxyl groups (acid number, AN) by a titration method. 1- and 4-month Orntide ms were prepared by a dispersion/solvent extraction/evaporation process and characterized for drug content (HPLC), bulk density (tapping method), particle size (laser diffraction method), surface morphology (scanning electron microscopy, SEM), and structural integrity of encapsulated peptide by Fourier Transform Matrix Assisted Laser Desorption mass spectrometry (FT-MALDI). Peptide binding to PLA and PLGA and non-specific adsorption to blank ms was studied in 0.1 M phosphate buffer pH 7.4 (PB) and 0.1 M acetate buffer pH 4.0 (AB). In vitro release of peptide was assessed in PB and AB. RESULTS: Mw for the PLGA copolymers varied from 10,777 to 31,281 Da and was 9,489 Da for PLA. AN was between 4.60 and 15.1 for the hydrophilic resomers and 0.72 for the hydrophobic 50:50 PLGA copolymer. Spherical ms (3.9 mu to 14 mu in diameter) with mostly nonporous surface and varying degree of internal porosity were prepared. FT-MALDI mass spectra of the extracted peptide showed that the encapsulation process did not alter its chemical structure. Peptide binding to PLGA and PLA and non-specific adsorption to blank PLGA ms were dependent upon pH and were markedly higher in PB than in AB. The initial in vitro release in PB varied from 0.5 to 26%/24 h but due to substantial binding of the peptide to the polymeric matrix the long-term release in PB could not be determined. Application of a dialysis method allowed for a more accurate determination of in vitro release and a good total drug recovery. CONCLUSIONS: Orntide acetate was successfully incorporated into PLA and PLGA ms and the 1- and 4-month in vitro release profiles were achieved by polymer selection and optimization of the manufacturing parameters.