利福平聚乳酸-羟基乙酸共聚物纳米粒的成型工艺及制剂学性质分析

目的优化利福平聚乳酸-羟基乙酸共聚物纳米粒(RFP-PLGA-NPs)的制备工艺,并分析其制剂学性质。方法以PLGA为载体,采用改良的自乳化溶剂蒸发法(M-SESD)制备RFP-PLGA-NPs。以粒径、包封率、载药量为指标,采用正交设计法优化处方和制备工艺。结果制备RFP-PLGA-NPs的优化条件为PLGA 100 mg,poloxsmer 188质量分数1.0%,丙酮与乙醇体积比3:1,有机相体积15 mL。按优化条件所制备的RFP-PLGA-NPs的粒径为(128.73±4.07)nm,多分散系数(PDI)为0.046～0.105,包封率(65.84±0.69)%,载药量(3.78±0.14)%。结论该工艺简单、稳定性好,为后续RFP-PLGA-NPs的体内研究奠定了基础。     

因子设计-效应面法优化紫杉醇聚乳酸-羟基乙酸纳米粒处方和制备工艺

目的:优化紫杉醇聚乳酸-羟基乙酸(PLGA)纳米粒处方和制备工艺.方法:以PLGA为载体,采用溶剂扩散法制备紫杉醇PLGA纳米粒,用32满因子设计实验,考察因素PLGA在有机相中的浓度和理论载药量对纳米粒的粒径、载药量和包封率的影响,实验数据分别采用线性方程和二次多项式拟合,根据最佳数学模型绘制效应面并选出最优处方.结果:2个影响因素和3个评价指标之间存在定量关系,最优处方为:紫杉醇的理论载药量为9.09%、有机相中PLGA浓度为2%,制备得到的纳米粒粒径为281 nm,实际载药量为7.73%,包封率为57.43%.结论:采用因子设计-效应面法完成了紫杉醇纳米给药系统的多目标同步优化.     

聚乙二醇-聚乳酸-羟基乙酸嵌段共聚物载药纳米粒制备方法的研究进展

目的:为聚乙二醇-聚乳酸-羟基乙酸(PEG-PLGA)嵌段共聚物载药纳米粒制备方法的进一步研究提供参考。方法:以"聚乙二醇-聚乳酸-羟基乙酸""嵌段共聚物""载药纳米粒制备方法""PEG""PLGA""PEG-PLGA"等为关键词,组合查询1998年1月-2017年1月在Pub Med、Springer Link、Science Direct、中国知网、万方、维普等数据库中的相关文献,对溶剂挥发法、沉淀法、自乳化溶剂扩散法、盐析法等制备方法进行综述。结果与结论:共检索到相关文献246篇,其中有效文献28篇。虽然载药纳米粒制备方法已经解决了操作、耗能及环境污染上的一些难题,但仍然存在常使用毒性较大含氯有机溶剂和难以工业化大生产等问题。前者可通过寻找毒性较小的有机溶剂(如丙酮、乙酸乙酯)来代替和通过对PLGA结构修饰基团或合成方法的改进使其可溶于毒性较小的有机溶剂加以解决;后者可通过研发新型辅料,或是改进制备工艺(如冻干)来改善纳米粒的稳定性和研发新型生产设备来解决。     

Box-Behnken设计-效应面法优化吴茱萸碱-羟基乙酸共聚物纳米粒处方及体外释药研究

目的：Box-Behnken设计-效应面法优化吴茱萸碱聚乳酸-羟基乙酸共聚物[poly （lactic-co-glycolic acid）,PLGA]纳米粒处方（吴茱萸碱-PLGA纳米粒）,考察体外释药行为。方法：单因素考察PLGA用量,油水体积比,泊洛沙姆188浓度,超声功率和时间等因素的影响,采用Box-Behnken响应面法优化吴茱萸碱-PLGA纳米粒处方。采用甘露醇为冻干保护剂,制备吴茱萸碱-PLGA纳米粒冻干粉末,并考察体外释药情况及释药模型。结果：吴茱萸碱-PLGA纳米粒最佳处方为：PLGA用量为445.1 mg、油水体积比1：5.2、泊洛沙姆188质量分数为1.2%。包封率和粒径分别为（75.73±1.33）%和（173.27±6.86） nm,与模型预测值接近。体外释药符合Higuchi模型：M_t/M_∞=0.109 9t^1/2+0.081 6,缓释特征明显。结论：Box-Behnken实验设计可用于吴茱萸碱-PLGA纳米粒处方研究,为进一步研究奠定了基础。     

聚乳酸-羟基乙酸纳米粒表面功能化修饰及其应用

聚乳酸-羟基乙酸(PLGA)纳米粒表面特性是影响其体内分布的重要因素,经表面修饰的PLGA纳米粒已广泛应用于靶向给药系统研究.本文综述了PLGA纳米粒表面修饰的方法,包括共价交联、静电作用及疏水作用力等,概述了表面修饰纳米粒在非特异性生物黏附和生物渗透、特异性靶向、延长体循环时间及稳定生物活性分子方面的应用.     

尼莫地平PEG-PLGA纳米粒的制备及其处方优化

目的：负载尼莫地平的聚乙二醇修饰的聚乳酸-羟基乙酸共聚物[poly （ethylene glycol-poly （lactin-co-glycolic acid）,PEG-PLGA）]纳米粒,并对其进行制备工艺、质量评价以及体外释放等相关性研究。方法：以PEG-PLGA为药物载体,采用乳化溶剂挥发法成功制备尼莫地平载药纳米粒。单因素实验和响应面法设计优化处方工艺,透射电子显微镜观察纳米粒形态,激光粒度仪测定其粒径和Zeta电位,HPLC法测定其包封率及载药量并考察其体外释药特性。结果：制备的尼莫地平纳米粒外观呈实心球体,大小均匀且分散性良好;平均粒径为（183.2±3.30） nm,PDI为（0.115±0.049）,Zata电位为（-11.78±2.16） mV;平均包封率为84.99%,平均载药量为2.45%;尼莫地平原料药在4 h时基本释放完全（达到95%左右）,而尼莫地平纳米粒在4 h时释放仅为43.9%,在第24 h时累计释放度达到（83.66±2.57）%。与对照组相比,制剂组释放缓慢,符合实验设计缓释的要求。结论：本实验成功制备了尼莫地平PEG-PLGA纳米粒,其体外释药具有明显缓释特征,为心脑血管疾病的治疗奠定了基础。     

载塞来昔布-聚乳酸/羟基乙酸共聚物纳米粒的制备及表征

目的:制备载塞来昔布-聚乳酸/羟基乙酸共聚物(PLGA)纳米粒,并对其进行表征。方法:采用乳化-溶剂蒸发法制备塞来昔布-PLGA纳米粒,以包封率、粒径为指标,首选Plackett-Burman试验设计筛选出对纳米粒性质影响显著的处方和工艺变量,然后对筛选出的变量(PLGA质量分数、超声功率、超声时间)应用Box-Behnken效应面法进一步优化,并进行验证。采用粒度分析仪测定最优处方工艺所制纳米粒的粒径分布和Zeta电位,采用透射电镜考察其形态,并考察纳米粒的体外释药行为和稳定性(25、5℃)。结果:最优处方工艺为PLGA质量分数30.0%、超声功率180 W、超声时间8 min;所制纳米粒的包封率和粒径分别为(85.7±4.1)%、(226.1±36.1)nm(n=3),粒径分布为(176.2±41.2)nm,多分散系数为0.211±0.021,Zeta电位为(-37.3±1.6)m V;电镜下微乳粒径均一,呈球状或椭圆形,24 h累积释放度为52.4%;纳米粒在5℃条件下放置3个月内稳定。结论:成功制得塞来昔布-PLGA纳米粒。     

乳酸-羟基乙酸共聚物纳米粒的制备及其表面修饰

目的:促进生物可降解聚合物乳酸-羟基乙酸共聚物(PLGA)纳米粒作为蛋白、多肽类药物投递载体的应用。方法:综述近几年乳酸-羟基乙酸共聚物纳米粒的制备方法及其参数,并概述其纳米粒的表面修饰手段。结果:乳酸-羟基乙酸共聚物纳米粒的制备方法主要包括乳化-溶剂挥发法、相转变法、乳化-扩散法、沉淀法、盐析法以及高压乳匀法。制备纳米粒的一个关键性参数是表面活性剂/稳定剂。纳米粒表面修饰最常用聚乙二醇。结论:乳酸-羟基乙酸共聚物纳米粒作为一种新型的给药系统富有前景,可广泛应用于亲水性和疏水性药物,尤其是蛋白、疫苗、生物大分子的给药。     

大黄素-聚乳酸-羟基乙酸共聚物纳米粒的制备

目的 制备大黄素-聚乳酸-羟基乙酸( emodin-polylactic-co-glycolic acid,EMD-PLGA NPs)共聚物纳米粒,观察其电镜形态、稳定性,测定粒径、包封率、载药量.方法 采用乳化-溶剂挥发法( emulsion solvent evaporation method)按照正交设计制备EMD-PLGA NPs并优化处方,透射电镜下观察纳米粒的外观形态,激光粒度仪检测纳米粒的大小、分布及zeta电位,沉降法观察稳定性,用紫外分光光度计测定大黄素纳米粒的吸光度以计算包封率、载药量.结果 得到最佳优化处方工艺条件,在最佳条件下制得大黄素纳米粒呈圆球状或椭圆状;粒径约( 100±50 )nm;分散体系的颗粒由上而下呈逐渐变淡的弥散分布,无明显的沉积物;包封率为(24.5±1.9)％,载药量为(18.5±3.7)％.结论 采用乳化-溶剂挥发法制备大黄素-PLGA纳米粒,该方法材料简单,便于操作,优于以往的固体脂质纳米粒法;制备的大黄素纳米粒粒径小、分布均匀、载药率较高,药物吸光度及稳定性等均符合要求,为进一步制备组织靶向药物的研究奠定了基础.     

利福平聚乳酸-羟基乙酸共聚物纳米粒雾化吸入给药肺靶向性研究

目的研究利福平聚乳酸-羟基乙酸共聚物纳米粒雾化吸入给药的肺靶向性。方法分别将利福平聚乳酸-羟基乙酸共聚物纳米粒混悬液(RFP-PLGA-NPs)和利福平注射液(RFP-Sol)以雾化吸入方式给予SD大鼠,在不同时间点测定利福平在大鼠肺组织中的浓度,计算相应药动学参数,比较2种制剂在肺组织中药动学过程,并评价靶向性。结果 RFP-Sol和RFP-PLGA-NPs的Tmax分别为(1.50±0.01)h和(2.00±0.08)h,Cmax分别为(0.83±0.07)mg.L 1和(5.02±0.05)mg.L 1,AUC0→∞分别为(6.24±0.24)mg.h.L 1和(35.80±6.34)mg.h.L 1,CL分别为(4.801±0.18)L.h 1.kg 1和(0.85±0.15)L.h 1.kg 1。通过对re和Ce等靶向性指标进行分析,RFP-PLGA-NPs在肺组织中的re和Ce均>1。结论与RFP-Sol相比,RFP-PLGA-NPs经雾化吸入给药后,明显提高了肺组织中药物的分布并且延缓消除,有显著的缓释性,从而降低药物对全身的不良反应,提高对肺结核的治疗作用。     

Development and characterization of poly(lactic-co-glycolic) acid nanoparticles loaded with copaiba oleoresin

Abstract

Copaiba oleoresin (CPO), obtained from Copaifera landgroffii, is described as active to a large number of diseases and more recently in the endometriosis treatment. In this work, poly(lactic-co-glycolic acid) (PLGA) nanoparticles containing CPO were obtained using the design of experiments (DOE) as a tool to optimize the production process. The nanoparticles optimized by means of DOE presented an activity in relation to the cellular viability of endometrial cells. The DOE showed that higher amounts of CPO combined with higher surfactant concentrations resulted in better encapsulation efficiency and size distribution along with good stability after freeze drying. The encapsulation efficiency was over 80% for all produced nanoparticles, which also presented sizes below 300?nm and spherical shape. A decrease in viability of endometrial stromal cells from ectopic endometrium of patients with endometriosis and from eutopic endometriotic lesions was demonstrated after 48?h of incubation with the CPO nanoparticles. The nanoparticles without CPO were not able to alter the cell viability of the same cells, indicating that this material was not cytotoxic to the tested cells and suggesting that the effect was specific to CPO. The results indicate that the use of CPO nanoparticles may represent a promising alternative for the treatment of endometriosis.     

不同表面活性剂修饰的汉防己甲素PLGA纳米粒制备表征及体外评价

目的:基于纳米粒的递送系统,以改善天然化合物汉防己甲素对肺癌的功效。方法:选取聚乙烯醇、普朗尼克-F127和双十二烷基二甲基溴化铵3种不同的稳定剂,采用单乳化扩散溶剂挥发法制备载汉防己甲素的PLGA纳米粒,考察不同稳定剂对载药纳米粒粒径、ζ电位以及对肺癌A549细胞摄取的影响。结果:2%,1%和0.1%浓度的PVA、PF127和DMAB制备的纳米粒呈表面光滑、大小均一的球形,粒径范围均控制在180~200nm;药物包封率为50%~60%;体外释放实验显示,在pH 7.4的PBS溶液中3组载药纳米粒均呈现缓慢持续释药;细胞学实验结果表明3组纳米粒给药系统均表现出比药物更强的抗肿瘤活性。结论:对PLGA进行表面修饰制备的纳米载体能使汉防己甲素的给药效率得到明显提升。     

Local drug delivery using poly(lactic-co-glycolic acid) nanoparticles in thermosensitive gels for inner ear disease treatment

Intratympanic (IT) therapies have been explored to address several side effects that could be caused by systemic administration of steroids to treat inner ear diseases. For effective drug delivery to the inner ear, an IT delivery system was developed using poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) and thermosensitive gels to maintain sustained release. Dexamethasone (DEX) was used as a model drug. The size and zeta potential of PLGA NPs and the gelation time of the thermosensitive gel were measured. In vitro drug release was studied using a Franz diffusion cell. Cytotoxicity of the formulations was investigated using SK-MEL-31 cells. Inflammatory responses were evaluated by histological observation of spiral ganglion cells and stria vascularis in the mouse cochlea 24 h after IT administration. In addition, the biodistribution of the formulations in mouse ears was observed by fluorescence imaging using coumarin-6. DEX-NPs showed a particle size of 150.0 ± 3.2 nm in diameter and a zeta potential of −18.7 ± 0.6. The DEX-NP-gel showed a gelation time of approximately 64 s at 37 °C and presented a similar release profile and cytotoxicity as that for DEX-NP. Furthermore, no significant inflammatory response was observed after IT administration. Fluorescence imaging results suggested that DEX-NP-gel sustained release compared to the other formulations. In conclusion, the PLGA NP-loaded thermosensitive gel may be a potential drug delivery system for the inner ear.     

Exploring the immunopotentiation of Chinese yam polysaccharide poly(lactic-co-glycolic acid) nanoparticles in an ovalbumin vaccine formulation in vivo

Biocompatible and biodegradable poly(lactic-co-glycolic acid) (PLGA) has been approved by the US Food and Drug Administration and has frequently been used to develop potential vaccine delivery systems. The immunoregulation and immunopotentiation of Chinese yam polysaccharide (CYP) have been widely demonstrated. In the current study, cell uptake mechanisms in dendritic cells (DCs) were monitored in vitro using confocal laser scanning microscopy, transmission electron microscopy, and flow cytometry. To study a CYP-PLGA nanoparticle-adjuvanted delivery system, CYP and ovalbumin (OVA) were encapsulated in PLGA nanoparticles (CYPPs) to act as a vaccine, and the formulation was tested in immunized mice. The CYPPs more easily underwent uptake by DCs in vitro, and CYPP/OVA could stimulate more effective antigen-specific immune responses than any of the single-component formulations in vivo. Mice immunized using CYPP/OVA exhibited more secretion of OVA-specific IgG antibodies, better proliferation, and higher cytokine secretion by splenocytes and significant activation of CD3⁺CD4⁺ and CD3⁺CD8⁺ T cells. Overall, the CYPP/OVA formulation produced a stronger humoral and cellular immune response and a mixed Th1/Th2 immune response with a greater Th1 bias in comparison with the other formulations. In conclusion, the data demonstrate that the CYPP-adjuvanted delivery system has the potential to strengthen immune responses and lay the foundation for novel adjuvant design.     

无稳定剂修饰的汉防己甲素PLGA纳米粒制备及体外评价

目的:制备无稳定剂修饰的汉防己甲素PLGA纳米粒,研究其理化性质及细胞毒和细胞摄取特性。方法:以聚乳酸-羟基醋酸共聚物(PLGA)为载体材料,采用无稳定剂修饰的纳米沉淀法制备汉防己甲素纳米粒;通过单因素试验考察不同制备工艺对纳米粒理化性质的影响;通过载药量、包封率、累积释药量等指标考察其载药特性;采用MTT比色法检测其对人肺腺癌细胞株A549的细胞毒性;采用共聚焦显微镜技术考察其细胞摄取特性。结果:无稳定剂修饰的汉防己甲素PLGA纳米粒平均粒径169.3 nm,与有稳定剂的汉防己甲素PLGA纳米粒相比外观无明显改变。在一定范围内,随着PLGA用量的增加,纳米粒的粒径呈上升趋势;随着投药量的增加,纳米粒的载药量显著增加,包封率下降。在pH7.4的释放介质中,纳米粒释慢释药,96 h累积释药率60.44%。细胞毒试验显示,当培养时间为8 h时,汉防己甲素组的细胞毒性大于汉防己甲素纳米粒组;当培养时间延长至24 h时,汉防己甲素纳米粒组的细胞活性明显低于纯药物组;高剂量的空白纳米粒组始终表现较低的细胞毒性。激光共聚焦电镜断层扫描显示汉防己甲素纳米粒能够较好的被细胞摄取。结论:制备的无稳定剂修饰的汉防己甲素PLGA纳米粒大小均一,包封率高,体外释药表现出较好的缓释效果,易被细胞摄取,对A549细胞的增殖有明显的抑制作用。     

壳聚糖包衣对胰岛素聚酯纳米粒胃肠道吸收的促进作用

目的研究壳聚糖包衣胰岛素乳酸/羟基乙酸共聚物(PLGA)纳米粒对胰岛素胃肠道吸收的促进作用。方法以双乳化法制备了胰岛素PLGA复乳,壳聚糖用作稳定剂,制备了包衣纳米粒;观察了粒子大小、表面形态及Zeta电位;测定了包封率;考察了体外释药行为;以糖尿病大鼠评价降血糖水平。结果包衣纳米粒粒度分布均匀,隐约可见层状结构,壳聚糖可改变粒子表面Zeta电位,提高包封率,降低突释;灌服10 u·kg^-1包衣纳米粒,14～16 h降血糖水平显著高于未包衣纳米粒(P＜0.05),药理相对生物利用度提高到15.4%。结论壳聚糖包衣聚酯纳米粒可以促进胰岛素胃肠道吸收。     

Visual Evidence of Acidic Environment Within Degrading Poly(lactic-co-glycolic acid) (PLGA) Microspheres

Purpose. In the past decade, biodegradable polymers have becomethe materials of choice for a variety of biomaterials applications. Inparticular, poly(lactic-co-glycolic acid) (PLGA) microspheres havebeen extensively studied for controlled-release drug delivery. However,degradation of the polymer generates acidic monomers, andacidification of the inner polymer environment is a central issue in thedevelopment of these devices for drug delivery. Methods. To quantitatively determine the intrapolymer acidity, weentrapped pH-sensitive fluorescent dyes (conjugated to 10,000 Dadextrans) within the microspheres and imaged them with confocalfluorescence microscopy. The technique allows visualization of thespatial and temporal distribution of pH within the degradingmicrospheres (1). Results. Our experiments show the formation of a very acidicenvironment within the particles with the minimum pH as low as 1.5. Conclusions. The images show a pH gradient, with the most acidicenvironment at the center of the spheres and higher pH near the edges,which is characteristic of diffusion-controlled release of the acidicdegradation products.     

Poly(lactic-co-glycolic acid) nanoparticles for sustained release of allyl isothiocyanate: characterization,in vitro release and biological activity

The objective of this study is to establish the ability of entrap allyl isothiocyanate (AITC) into polymeric nanoparticles to extend its shelf life and enhance its antiproliferative properties. Natural compounds, such as AITC, have showed multi-targeting activity resulting in a wide-range spectrum of therapeutic properties in chronic and degenerative diseases, conversely with most current pharmaceutical drugs showing single targeting activity and often result in drug resistance after extended administration periods. Apparently, AITC-loaded poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) reduced AITC degradation and volatility and were able to extend AITC shelf life compared with free AITC (65% vs. 20% in 24?h, respectively). Cell viability and uptake of AITC-loaded nanoparticles were studied in vitro, showing that the protection and sustained release of AITC from polymeric NPs involved a larger toxicity of tumoral cells. These nanoparticles could be used as protective systems for enhancing a biological activity.     

Preparation,characterization, and anticancer efficacy of evodiamine-loaded PLGA nanoparticles

Evodiamine (EVO) is a plant-derived indolequinazoline alkaloid with potential anticancer activity. However, low bioavailability caused by its poor water solubility limits it anticancer efficacy in clinic. To enhance the solubility and improve the bioavailability of EVO, a delivery system based on poly (lactic-co-glycolic acid) (PLGA) nanoparticles loaded with EVO (EVO-PLGA NPs) for treating breast cancer was prepared in this study. The physicochemical characterization and in vitro antitumor evaluation of EVO-PLGA NPs were determined. EVO-PLGA NPs could persistently control the release of EVO for 180?h. 3-[4,5-Dimethyl-2-thiazolyl]-2,5-diphenyl tetrazolium bromide (MTT) assessment and colony formation assay showed that EVO-PLGA NPs could enhance the toxicity and the proliferation inhibition effect of EVO on MCF-7 breast cancer cells. EVO-PLGA NPs did not strengthen G2/M arrest effect of EVO-treated cells after 24h incubation. Meanwhile, EVO-PLGA NPs could increase the expression of cyclin B1 and decrease the expression of β-actin. Taken together, these results suggested that -PLGA NPs is promising for improving anticancer efficacy of EVO in breast cancer therapy.     

姜黄素PLGA纳米粒的制备及制剂学性质分析

目的制备姜黄素(Curcumin,Cur)聚乳酸羟基乙酸共聚物(PLGA)纳米粒(Cur-PLGA-NPs)并对其理化性质进行考察。方法采用改良的自乳化溶剂挥发法制备纳米粒,通过正交设计,以粒径、包封率和载药量为评价指标优化处方工艺。结果制备Cur-PLGA-NPs的优化条件为PLGA 100 mg,泊洛沙姆188浓度1.0%,丙酮与乙醇体积比3∶1,有机相体积15 m L。按优化条件所制备的Cur-PLGA-NPs粒径为(120.33±2.44)nm,多分散系数为0.10±0.02,包封率为84.50%±1.13%,载药量为4.75%±0.22%。结论采用改良的自乳化溶剂挥发法成功制备了Cur-PLGA-NPs,为后续"纳米粒-脂质体系统"的研究奠定了基础,有望实现药物在肝脏的浓集。