脂质体物理稳定性和包封率的影响因素

脂质体制备的难点在于改善物理稳定性和提高包封率.现从脂质体的常用制备方法、投料和投料比、制备过程中的条件控制及贮存条件等方面考察其对脂质体的物理稳定性和包封率的影响.     

长循环脂质体的研究进展

脂质体的稳定性脂质体的物理、化学和生物学稳定性三个方面。其中生物学稳定性是脂质体在生物样品内保持长循环的关键,制备长循环脂质体是实现脂质体许多性质的前提和基础。本文从脂质体的物理、化学特性,膜材组成及构造等几个方面综述了制备长循环脂质体的基本原理,制备手段和方法。     

紫草素外用脂质体搽剂制备及稳定性研究

目的制备紫草素脂质体搽剂,并考察稳定性。方法以胆固醇、卵磷脂等脂溶性材料为基质制备紫草素脂质体搽剂,以HPLC进行稳定性考察的含量测定。结果在优化条件下制备的紫草素脂质体搽剂符合质量标准要求,考察18个月紫草素含量无显著变化。结论该制备工艺简便可行,产品稳定性好。     

洛伐他汀自组装前体脂质体的制备及其理化性质的研究

目的:为研究洛伐他汀新剂型,制备洛伐他汀新型前体脂质体,并对其质量进行考察。方法:采用一种新型前体脂质体制备方法将洛伐他汀制成自组装前体脂质体,对水合后脂质体的形态、粒径、Zeta电位、包封率、自组装速度、稳定性等进行考察,验证这种新型前体脂质体制备方法用于制备洛伐他汀脂质体的可行性。结果:所形成的洛伐他汀脂质体包封率为95.4%±6.7%,平均粒径为(327.4±29.6)nm,Zeta电位值为-(22.4±1.5)mV。洛伐他汀自组装前体脂质体可在60 s内自发形成脂质体并达到分散平衡;以人工胃液为稀释介质,洛伐他汀脂质体在12 h内稳定。结论:采用新型前体脂质体制备方法可将洛伐他汀制成洛伐他汀脂质体,形成的脂质体包封率较高且具有良好的稳定性。     

脂质体制备方法及相关性质的研究概况

脂质体制备剂技术发展迅速并逐渐完善,其多种制备方法各有利弊.评价脂质体质量的指标有外观、粒径分布、包封率和渗漏率等;稳定性也是制备脂质体过程中需要考虑的另一个重要因素.逆相蒸发法是制备脂质体的一种常用方法.本文从近几年逆相蒸发法制备脂质体及其质量评价和稳定性研究三方面作一综述.     

不同类型的磷脂对三氧化二砷脂质体外观稳定性的影响

目的:研究不同类型的磷脂对三氧化二砷(As2O3)脂质体外观稳定性的影响。方法:采用A、B厂家生产的浓缩磷脂和C、D厂家生产的粉状磷脂,分别应用薄膜分散法、乙醚注入法、逆相蒸发法制备脂质体,以样品是否发生分层凝聚现象为指标观察其在1、7d,1、6、12个月内的外观稳定性。结果:A、B2厂家磷脂制备的As2O3脂质体在1年内全部出现分层凝聚现象,C、D厂家磷脂制备的As2O3脂质体保存1年仍未见分层凝聚现象。结论:C、D2个厂家所生产的磷脂制备的As2O3脂质体稳定性更好,不同类型的磷脂对所制备的脂质体的外观稳定性具有一定影响。     

硫酸铵梯度法制备伊立替康脂质体及稳定性研究

目的：制备盐酸伊立替康脂质体并考察提高脂质体稳定性的方法。方法：采用硫酸铵梯度法制备盐酸伊立替康脂质体。以粒径、外观、颜色、渗漏率作为指标，考察盐酸伊立替康脂质体的物理和化学稳定性。结果：硫酸铵梯度法制备的盐酸伊立替康脂质体呈圆球形，平均粒径为600nm，稳定性较好。结论：盐酸伊立替康脂质体不耐高温，将其制成冻干粉剂可显著提高药物稳定性。     

干扰素脂质体制备方法概述

目的 介绍近年来干扰素脂质体的常用制备方法。方法 检索国内外文献资料，对已开展的几种干扰素脂质体制备方法特点进行归纳分析。结果 国内外学者分别采用不同方法制备了干扰素脂质体，但普遍存在包封率低、工业化生产困难等问题。结论 干扰素脂质体制备的关键是提高包封率和稳定性，探索工业化生产的可行性。     

脂质体处方和制备方法对阿昔洛韦棕榈酸酯脂质体稳定性的影响

目的　研究不同处方组成和制备方法对阿昔洛韦棕榈酸酯脂质体在 4℃和 2 5℃分别贮存 90d和 180d后的稳定性的影响。方法　用卵磷脂 (PC) 胆固醇 (CH) 磷脂酰丝氨酸 (PS) ,卵磷脂 (PC) 胆固醇 (CH) 硬脂酰胺 (SA) ,卵磷脂 (PC) 胆固醇 (CH) 胆固醇硫酸酯 (CS) ,神经酰胺 (CM) 胆固醇 (CH) 棕榈酸 (PA) 胆固醇硫酸酯 (CS) ,以薄膜分散法、逆向蒸发法和去水化 水化法 ,分别制备多室脂质体 (MLV)、大单室脂质体 (LUV)、去水化 水化脂质体(DRV) ,以平均粒径、渗漏率、pH值和Zeta电位 4个指标考察不同贮存条件下脂质体的稳定性。结果　脂质体稳定性顺序依次为 ,对不同脂质体处方 :PC CH CS >CM CH PA CS >PC CH PS >PC CH SA ;对不同制备方法 :LUV优于MLV和DRV ;4℃时脂质体的稳定性优于 2 5℃时的脂质体。结论　脂质体的稳定性与制剂处方和制备方法密切相关。     

甘草次酸阳离子脂质体的制备及稳定性考察

目的:制备甘草次酸阳离子脂质体,并研究其稳定性。方法:用乙醇注入法制备甘草次酸阳离子脂质体。考察其粒径、包封率、过氧化值、在血浆中的稳定性和放样稳定性等性质。结果:所得脂质体的粒径小而均匀,呈球形和类球形,包封率为(91.6±1.2)%;离心加速试验结果显示脂质体的稳定性参数KE值较小,脂质体在血浆中释放缓慢,在4℃下放置6个月,其外观、包封率、粒径等各项指标无明显改变。结论:制得的甘草次酸脂质体包封率较高,稳定性良好。     

Encapsulation,Stability and In-vitro Release Characteristics of Liposomal Formulations of Colchicine

The severe toxicity and low therapeutic index of colchicine limit its therapeutic use. Encapsulation in liposomes might reduce these toxic effects. The objective of this study was to determine the factors influencing encapsulation of colchicine in liposomes and to optimize the encapsulation parameters. Colchicine was encapsulated in multilamellar liposomes and large unilamellar liposomes prepared using various phospholipids. The effects of method of preparation, type of vesicle, charge, and concentration of cholesterol on encapsulation of colchicine in liposomes were investigated. Also, stability of colchicine under stress conditions and at various temperatures, and in-vitro release characteristics were determined. A significant difference in encapsulation of colchicine in multilamellar liposomes was observed when prepared by two different methods. Induction of charge on the liposome surface increased encapsulation of colchicine in multilamellar liposomes, but did not affect large unilamellar liposomes. The liposome preparations could withstand simulated transport conditions and frequent changes in temperature. Particle size and concentration of colchicine did not change significantly during storage at various temperatures for six months. In order to retain encapsulated colchicine in liposomes, storage at or below room temperature was found to be suitable. In-vitro release of colchicine from large unilamellar liposomes was biphasic and was influenced by two rate-limiting barriers, the dialysis membrane and the liposome bi-layers. For optimum encapsulation and stability of colchicine liposomes were prepared from a mixture of 1,2-distearoyl-sn-glycero-3-phosphocholine, cholesterol and either stearylamine or dicetyl phosphate.     

非特异靶向荷正电高分子磷脂脂质体的构建和体外评价

采用一种新设计的末端带有枝状结构寡赖氨酸聚乙二醇高分子磷脂为主要功能性辅料, 依照常规薄膜-水合和后续高分子插入两种方法制备了系列外表面带正电荷的高分子脂质体。激光衍射粒径仪研究证明, 常规脂质体制备方法和后续高分子插入都可以制备纳米、粒径均匀、外表面携带不同密度正电荷的高分子磷脂脂质体, 正电荷密度不同并不影响脂质体的粒径和分布。后续高分子插入过程不影响脂质体的载药工艺, 不干扰脂质体的载药量, 不引起脂质体的形态和粒径变化, 也不诱发脂质体内部包裹的药物早期泄漏。体外细胞学实验证明这种荷正电高分子脂质体局部电荷密度高, 对细胞有显著非特异性靶向作用。     

Increased intracellular targeting to airway cells using octaarginine-coated liposomes: in vitro assessment of their suitability for inhalation

Delivery of macromolecular drugs to airway cells after inhalation can be limited by rapid clearance, in vivo degradation, and poor intracellular targeting. Liposome carriers offer an effective method of improving drug stability, but conventional liposomes have limited intracellular targeting capacity and are cleared rapidly by the lungs. Further modification is required to improve liposome-cell interaction and intracellular targeting. Therefore, we proposed conjugating three arginine-rich membrane translocating peptides, namely, HIV-TAT, Antennapedia, and octaarginine, to neutral liposomes as a biocompatible alternative to cationic lipids for intracellular delivery of macromolecules to airway cells. Conjugation did not significantly affect liposome stability, and each system was nebulized to produce aerosols of mean aerodynamic diameter < 1.5 microm. The peptides caused a significant (p < 0.05) increase in liposome-airway cell association compared to untagged liposomes and to DOTAP liposomes. Up to 30% of the peptide-conjugated liposomes added were bound and internalized (via a temperature-dependent, endocytic process) after just 2 h. The novel carriers all delivered encapsulated dextrans rapidly and efficiently to the cytoplasm of Calu-3 cells. Once internalized by the cells, the modified carriers localize for the most part in the cytoplasm with only a small amount of nuclear localization. These peptide-conjugated liposomes were significantly (p < 0.05) less toxic than DOTAP liposomes with octaarginine-coated liposomes the least toxic. These systems, particularly octaarginine-coated liposomes, offer many advantages for drug delivery to airway epithelial cells including increased stability, improved cell binding, and cell uptake with an improved toxicity profile.     

脂质体处方和制备方法对阿昔洛韦棕榈酸酯脂质体稳定性的影响

目的研究不同处方组成和制备方法对阿昔洛韦棕榈酸酯脂质体在4℃和25℃分别贮存90 d和180 d后的稳定性的影响。方法用卵磷脂(PC)/胆固醇(CH)/磷脂酰丝氨酸(PS),卵磷脂(PC)/胆固醇(CH)/硬脂酰胺(SA),卵磷脂(PC)/胆固醇(CH)/胆固醇硫酸酯(CS),神经酰胺(CM)/胆固醇(CH)/棕榈酸(PA)/胆固醇硫酸酯(CS),以薄膜分散法、逆向蒸发法和去水化/水化法,分别制备多室脂质体(MLV)、大单室脂质体(LUV)、去水化/水化脂质体(DRV),以平均粒径、渗漏率、pH值和Zeta电位4个指标考察不同贮存条件下脂质体的稳定性。结果脂质体稳定性顺序依次为,对不同脂质体处方:PC/CH/CS>CM/CH/PA/CS>PC/CH/PS>PC/CH/SA;对不同制备方法:LUV优于MLV和DRV;4℃时脂质体的稳定性优于25℃时的脂质体。结论脂质体的稳定性与制剂处方和制备方法密切相关。     

盐酸莫西沙星脂质体的制备及包封率测定方法研究

目的：制备盐酸莫西沙星脂质体,建立盐酸莫西沙星脂质体包封率测定方法。方法：乙醇注入法制备盐酸莫西沙星脂质体,正交试验优选脂质体的最佳处方。采用葡聚糖凝胶柱法、超滤离心法分离脂质体与游离药物,并进行方法学考察,优选出测定盐酸莫西沙星脂质体包封率的方法。结果：盐酸莫西沙星脂质体的最佳处方为：卵磷脂与胆固醇比为 3：1,药脂比为 1：7,水合介质中聚山梨酯20的用量为1%,优化后的包封率为90.73%。葡聚糖凝胶柱法和超滤离心法都能将脂质体与游离药物分离,葡聚糖凝胶柱法的平均柱加样回收率为85.54%~88.15%,超滤离心法的平均加样回收率为94.40%~97.35%。结论：盐酸莫西沙星脂质体的制备工艺稳定,包封率较高。葡聚糖凝胶柱法不适于盐酸莫西沙星脂质体的包封率测定,超滤离心法可高效、准确、方便地测定盐酸莫西沙星脂质体包封率。     

Studies on the carboxymethyl chitosan-containing liposomes for their stability and controlled release of dapsone.

Stable liposomes containing carboxymethyl chitosan (CMC) were prepared and characterized. CMC was introduced in the phosphatidyl choline (PC) liposomes by different methods; firstly, CMC in a free state in the aqueous phase; secondly as a coat (coupled); and finally as a conjugate of dapsone. The stability of liposomes was assessed by their disintegration in ethanol and surfactants. Both hydrophilic bromothymol blue and lipophilic dapsone were encapsulated in these liposomes and their in vitro release studies were carried out at 37 degrees C using different media, namely, phosphate buffer (pH 7.4), 0.02 N-HCl and 1% mouse plasma. The conjugate of dapsone with CMC present in PC liposomes gave the best results in its stability as compared to other modified liposomes. The release data of dapsone also confirmed the results of the stability studies on liposomes. CMC-dapsone conjugate released the dapsone much slower in all three media than did PCCMC and PCCMC-coat liposomes.     

卡波姆包衣姜黄素脂质体的制备及体外黏附性考察

目的探讨提高难溶性药物口服生物利用度的方法。方法采用薄膜分散法制备姜黄素脂质体,采用孵育法对姜黄素脂质体进行卡波姆包衣并考察姜黄素脂质体包衣前后稳定性、包封率及相对包衣率的变化,采用离体大鼠小肠孵育法考察卡波姆包衣姜黄素脂质体体外黏附性。结果卡波姆包衣对脂质体的稳定性影响较大,当卡波姆的质量浓度为5.0 g.L-1时脂质体最稳定;脂质体包衣后包封率略有下降,相对包衣率随着卡波姆质量浓度的增大而增大;质量浓度同为5.0 g.L-1的条件下,卡波姆包衣脂质体的体外生物黏附性比壳聚糖包衣的体外生物黏附性大,未包衣的脂质体体外生物黏附性很小。结论作为药物载体,卡波姆包衣脂质体具备了难溶性药物姜黄素口服给药的条件,将有很好的应用前景。     

类脂囊泡在不同给药途径中的研究进展

纳米载体具有靶向递送药物至特定部位的潜力,因此纳米载体的开发一直受到广泛关注。近10年里,制备基于表面活性剂的纳米囊泡以改善药物递送,引起了研究者们的兴趣。类脂囊泡由非离子表面活性剂在水性介质中自组装形成,具有既能包裹亲水性化合物又能包裹亲脂性化合物的囊泡结构,广泛应用于各种给药途径。与脂质体相比,类脂囊泡不仅具有与其相似的优点,如既能装载亲水性药物又能装载亲脂性药物,而且类脂囊泡的制备方法更简单,制备原料价格更便宜,稳定性更好,克服了脂质体的主要缺点。本文综述了类脂囊泡各制备方法的优缺点及其在不同给药途径中的研究进展。     

Liposomes containing drugs for treatment of vaginal infections

To develop a novel vaginal delivery system, able to effectively deliver entrapped drugs during an extended period of time at the site of action, liposomes made of phosphatidylcholine were prepared by two different methods, namely the polyol dilution method and the proliposome method. Liposomes containing three commonly applied drugs in the treatment of vaginal infections: clotrimazole, metronidazole and chloramphenicol were tested for in vitro stability (in buffers at pH 4.5 and 5.9 representing pre- and postmenopausal vaginal pH). In situ stability (in the presence of cow vaginal mucosa) showed that after 6 h incubation (at 37°C), liposomes retained more than 40% of originally entrapped clotrimazole, 28% of entrapped metronidazole or 37% of entrapped chloramphenicol. In vitro and in situ stability studies confirmed the applicability of liposomes as a carrier system for vaginal delivery. Even after 24 h of incubation in the presence of vaginal mucosa liposomes retained sufficient amounts of entrapped drugs.     

Liposomes with nifedipine and nifedipine-cyclodextrin complex: calorimetrical and plasma stability comparison

Inclusion complexes of nifedipine with 2-hydroxypropyl-ß-cyclodextrin (HPβCD) were formed by the spray- and freeze-drying methods. Nifedipine or its inclusion complexes (Nifedipine-CD complex I and II) were incorporated into liposomes prepared by the ethanol injection method. The highest entrapment value (77.7% of the starting material) was achieved for liposomes with N-CD complex II. The interaction of nifedipine with lipid bilayers was measured calorimetrically. DPPC liposomes mixed with nifedipine or N-CD complex II showed a slight shift of the transition temperature of DPPC towards lower temperatures compared to DPPC liposomes alone or mixed with HPßCD. However, with nifedipine, an additional transition peak was seen at lower temperatures in the second and all subsequent scans which could not be detected for the N-CD complex. Plasma stability studies showed that liposomes containing N-CD complex II are more stable than liposomes containing nifedipine. Encapsulation of drug-cyclodextrin complexes into liposomes can increase the entrapment of the lipophilic drug and reduce its release from the carrier.