药物纳米载体——聚合物胶束的研究进展

目的对目前聚合物胶束作为药物纳米载体的国内外研究进展进行综述。方法参考近年来国内外文献50篇,从聚合物胶束的类别和构成,药物的包载方法,药物从聚合物胶束中的释放,聚合物胶束的稳定性,聚合物胶束的表征,聚合物胶束对药物的药动学和体内分布的影响以及聚合物胶束作为药物载体的应用等几个方面系统地介绍了其研究进展。结果聚合物胶束包括自聚集胶束,单分子胶束和交联的胶束,可采用化学结合法、物理包载和聚离子复合法包载药物;药物分子在聚合物胶束中的分布以及聚合物的降解行为决定了药物的释放速度;聚合物胶束的热力学和动力学稳定性与其结构组成密切相关;载药聚合物胶束可改变药物的药动学和体内分布;目前聚合物胶束已被用于作为肿瘤药物、难溶性药物的载体,也可作为药物药物经皮传递载体和药物的缓释载体,发展前景较好,但同时也面临挑战。结论聚合物胶束作为药物的纳米载体具有广泛的应用前景。     

和厚朴酚泊洛沙姆F-127胶束的制备及其体外抗肿瘤研究

目的以泊洛沙姆F－127为载体制备一种新型的和厚朴酚胶束制剂,以提高其抗肿瘤效果。方法选用泊洛沙姆F－127为药物载体,采用自组装法制备和厚朴酚胶束制剂,通过透射电镜观察和厚朴酚胶束的形貌,采用紫外分光光度法测定载药量、药物包封率以及体外药物释放行为。采用MTT法检测和厚朴酚及其和厚朴酚胶束制剂对BGC－823人胃癌细胞的抑制作用。结果本研究所制备的和厚朴酚胶束纳米制剂,具有壳．核的球型结构。纳米粒子分布较窄,平均粒径为28．7nm。和厚朴酚与泊洛沙姆F－127的投料比影响胶束制剂载药量,随着和厚朴酚与泊洛沙姆F-127的投料比从1：10增加到1：2．5,载药胶束的载药量从（8．4±1．6）％增加到（25．7±2．7）％,而包封率维持在97％左右。体外释放结果显示和厚朴酚可以缓慢地从泊洛沙姆F-127胶束中释放出来。体外抗肿瘤实验结果显示：相比于溶液剂型的和厚朴酚,和厚朴酚／泊洛沙姆F-127胶束具有更好的体外抗BGC．823人胃癌细胞效果。结论和厚朴酚／泊洛沙姆F-127胶束是一种新型的和厚朴酚纳米制剂,能有效提高体外抗BGC．823人胃癌细胞效果。     

聚氨基酸胶束在肿瘤治疗中的研究进展

聚氨基酸胶束是一类新型的聚合物胶束,具有高效、长效及药量高载等特点。抗肿瘤药物通过化学结合或物理包裹的方式进入胶束内部,具有较高的稳定性。同时,在EPR(Enhanced Permeability and Retention,EPR)效应作用下,聚氨基酸胶束纳米粒可以有效地蓄积于肿瘤组织中达到很好的抗肿瘤效果,并减少药物在其他正常组织中的分布而降低毒副作用。本文综述了聚天冬氨酸、聚谷氨酸和聚赖氨酸三类聚氨基酸胶束作为抗肿瘤药物载体的理化性质、特点及其相关临床研究进展,对各个研究实例进行简要介绍。     

姜黄素纳米胶束的制备及体外抗肿瘤作用研究

目的 制备姜黄素(Cur)/甲氧基聚乙二醇-聚己内酯(MP)载药纳米胶束,并研究其体外抗肿瘤作用。方法 采用薄膜分散法制备Cur/MP纳米胶束,筛选不同药材质量比优化处方,在扫描电镜下观察载药纳米胶束的形态;采用CCK-8法考察Cur、Cur/MP胶束对人非小细胞肺癌A549细胞的抑制率;以香豆素6为荧光探针考察细胞对胶束的摄取行为。结果 按最优处方制备3批胶束的平均粒径为35.71±0.2 nm,平均电位为-16.8±0.2 mV,平均包封率为97.52%±1.00%,平均载药量5.25%±0.80%;Cur/MP胶束在72 h内释放度最大可达74.16%,释放缓慢,无突释现象,遵循一级动力学方程;与Cur溶液比较,Cur/MP纳米胶束对A549细胞的抑制作用增强;荧光显微镜下可观察到,随着时间的延长,细胞对药物的摄取增加。结论 Cur/MP胶束制备工艺简单,可增强药物对A549细胞的抑制作用;聚合物纳米胶束的pH敏感性有利于其在体内肿瘤组织中的蓄积及肿瘤细胞内的摄取。     

聚古罗糖醛酸硫酸酯-铜纳米胶束制备及抗肿瘤活性研究

目的 制备1种基于化学动力学疗法的聚古罗糖醛酸硫酸酯(PGS)-铜纳米胶束,进行抗肿瘤活性研究。方法 采用聚离子复合法,将PGS与铜离子及过氧化氢反应制备聚电解质纳米胶束PGS-Cu,分光光度法测定铜离子含量和羟基自由基,CCK-8法测定细胞存活率。结果 制备的PGS-Cu纳米粒径为(109.54±14.29) nm,分布系数为0.23±0.02,Zeta电位为(-47.58±1.71) mV。酸性环境下,PGS-Cu纳米胶束铜离子累积释放量显著高于中性环境,并产生·OH。100μg·mL^-1的PGS-Cu纳米胶束作用下,人源三阴性乳腺癌细胞(MDA-MB-231)、小鼠乳腺癌细胞(4T1)和小鼠正常成纤维细胞(NIH/3T3)的存活率分别为14.87%、62.24%和90.77%,表明PGS-Cu纳米胶束对乳腺癌细胞有显著的细胞毒性,且对MDA-MB-231细胞抑制效果最佳。此外,4T1细胞在pH 7.4和6.0时的存活率分别为62.24%和18.33%,说明该纳米胶束具有pH响应性。结论 成功构建了1种基于化学动力学疗法、以多糖为载体的聚电解纳米胶束,该纳米胶...     

基于壳聚寡糖的黄芩苷固体分散体的研究

目的将壳聚寡糖应用于黄芩苷的制备,以提高药物的体外溶出度。方法以壳聚寡糖为载体,采用喷雾干燥法制备黄芩苷固体分散体,对药物与载体不同比例制备的固体分散体的溶出行为进行了比较研究,并进行物相分析。结果黄芩苷和壳聚寡糖按1∶6比例制备的固体分散体在30 min时药物的体外累积溶出度为94.25%;经差示扫描量热法(DSC)、扫描电镜法(SEM)和X-射线粉末衍射法(XRD)等分析,固体分散体中黄芩苷以非晶形态高度分散;傅里叶红外光谱扫描(IR)结果表明壳聚寡糖与黄芩苷之间存在相互作用。结论以壳聚寡糖为载体制备的固体分散体能显著改善黄芩苷的溶出度;壳聚寡糖作为一种新型固体分散体载体具有实际应用价值。     

紫杉醇自组装核壳型纳米胶束的制备与性能

本文合成了聚乙二醇-聚谷氨酸苄酯(polyethylene glycol-polybenzyl-L-glutamate， PEG-PBLG)两亲嵌段共聚物， 并采用超微透析法制备了紫杉醇/PEG-PBLG核壳型纳米胶束。通过高效液相色谱测定了胶束的载药量及药物包封率； 采用动态光散射法测定了胶束的粒径及分布； 通过体外试验研究了紫杉醇/PEG-PBLG胶束的释药特性； 采用四噻唑蓝法考察了紫杉醇/PEG-PBLG胶束的体外细胞毒性； 通过裸鼠的抑瘤试验评价了紫杉醇胶束对人肝癌细胞的疗效。结果表明， PEG-PBLG胶束能包埋疏水性药物紫杉醇； 紫杉醇/PEG-PBLG胶束的粒径为80～265 nm， 且随着载体共聚物PBLG嵌段相对分子质量的升高而增大； 紫杉醇/PEG-PBLG胶束的体外释放具有缓释特性； 当紫杉醇浓度大于20 μg·mL^-1时， 紫杉醇/PEG-PBLG胶束的细胞毒性低于相应浓度的紫杉醇/聚氧乙烯蓖麻油注射剂(P<0.05)， 紫杉醇/PEG-PBLG胶束具有与紫杉醇/聚氧乙烯蓖麻油注射剂相似的抑制肿瘤作用。综上所述， 紫杉醇/PEG-PBLG纳米胶束具有较均匀的粒径及粒径分布、 缓释特性、 低毒和较好的抗肿瘤作用。     

聚乙二醇接枝壳聚糖聚离子胶束的制备与体外表征研究

目的制备载有甘草酸二铵(DG)的聚乙二醇接枝壳聚糖(mPEG-CS)聚离子胶束,考察胶束的理化性质及体外释放机制.方法通过壳聚糖烷基化合成mPEG-CS,以三聚磷酸钠为引发剂,利用静电相互作用制备载有DG的mPEG-CS聚离子胶束.考察胶束的形态、粒径和zeta电位.用透析袋法研究载药胶束在不同介质中的释放动力学.结果制得胶束的平均粒径为(38.2±0.9)nm;包封率为(97.6±0.7)%;胶束的稳定性良好;胶束的释放与释放介质的种类、pH值和浓度有关.结论mPEG-CS是一种良好的制备聚离子胶束的高分子材料,聚离子胶束是离子型药物的良好载体.     

载地塞米松聚合物胶束的制备及其性质

目的 制备具有良好生物相容性的地塞米松聚合物胶束,为血管炎症提供一种高效的治疗方法.方法 以聚己内酯-聚乙二醇载体和聚己内酯-聚甲基丙烯酸乙酯阳离子载体为材料制备地塞米松载药聚合物胶束.对所制备的载药聚合物胶束的形态、粒径、PDI、Zeta电位、包封率及载药量进行表征.以人脐静脉内皮细胞为细胞模型,采用噻唑蓝法考察载药...     

纳米胶束作为药物载体的研究进展

药剂学中以表面活性剂或高分子载体材料形成的胶束为载体制成的药物胶柬制剂正受到越来越多的关注,而粒径为纳米尺寸的纳米胶束作为药物的载体具有许多独特的优势,如缓控释及靶向特性、与细胞和组织的生物相容性等优点,在新型载药系统领域显示了良好的应用前景。本文简要综述了纳米胶束的性质、形成机理、载体材料、制备方法、体内外释药特性及在药物载体方面的应用研究。     

壳聚糖微球制备方法研究

综述近年来国内外壳聚糖微球制备方法的研究进展,其中主要介绍交联法、凝聚法、乳化-溶剂蒸发法、壳聚糖溶液包衣法、壳聚糖微球乙酰化法、喷雾干燥法等。     

Optimization of Chitosan Succinate and Chitosan Phthalate Microspheres for Oral Delivery of Insulin using Response Surface Methodology

In the present study, a Box-Behnken experimental design was employed to statistically optimize the formulation parameters of chitosan phthalate and chitosan succinate microspheres preparation. These microspheres can be useful for oral insulin delivery system. The effects of three parameters namely polymer concentration, stirring speed and cross linking agent were studied. The fitted mathematical model allowed us to plot response surfaces curves and to determine optimal preparation conditions. Results clearly indicated that the crosslinking agent was the main factor influencing the insulin loading and releasing. The in vitro results indicated that chitosan succinate microspheres need high amount of crosslinking agent to control initial burst release compared to chitosan phthalate microspheres. The reason may be attributed that chitosan succinate is more hydrophilic than chitosan phthalate. The relative pharmacological efficacy for chitosan phthalate and chitosan succinate microspheres (18.66 ± 3.84%, 16.24 ± 4%) was almost three-fold higher than the efficacy of the oral insulin administration (4.68 ± 1.52%). These findings suggest that these microspheres are promising carrier for oral insulin delivery system.     

Optimization of chitosan succinate and chitosan phthalate microspheres for oral delivery of insulin using response surface methodology

In the present study, a Box-Behnken experimental design was employed to statistically optimize the formulation parameters of chitosan phthalate and chitosan succinate microspheres preparation. These microspheres can be useful for oral insulin delivery system. The effects of three parameters namely polymer concentration, stirring speed and cross linking agent were studied. The fitted mathematical model allowed us to plot response surfaces curves and to determine optimal preparation conditions. Results clearly indicated that the crosslinking agent was the main factor influencing the insulin loading and releasing. The in vitro results indicated that chitosan succinate microspheres need high amount of crosslinking agent to control initial burst release compared to chitosan phthalate microspheres. The reason may be attributed that chitosan succinate is more hydrophilic than chitosan phthalate. The relative pharmacological efficacy for chitosan phthalate and chitosan succinate microspheres (18.66 +/- 3.84%, 16.24 +/- 4%) was almost three-fold higher than the efficacy of the oral insulin administration (4.68 +/- 1.52%). These findings suggest that these microspheres are promising carrier for oral insulin delivery system.     

Simulation of skin permeability in chitosan membranes

To provide an alternative means of evaluating transdermal drug delivery systems, membranes of chitosan were developed. The membranes were prepared by cast-drying method. The effects of chitosan concentration, sodium tripolyphosphate (NaTPP) concentration and crosslinking (CL) time on flux and lag time were studied using central composite design. It was observed that chitosan membrane at a particular composition simulated the permeation of diclofenac sodium through rat skin The mathematical model developed in the present study can be used to simulate the permeation of drugs through different species of animal skins.     

Hydrogel nanoparticles in drug delivery

Hydrogel nanoparticles have gained considerable attention in recent years as one of the most promising nanoparticulate drug delivery systems owing to their unique potentials via combining the characteristics of a hydrogel system (e.g., hydrophilicity and extremely high water content) with a nanoparticle (e.g., very small size). Several polymeric hydrogel nanoparticulate systems have been prepared and characterized in recent years, based on both natural and synthetic polymers, each with its own advantages and drawbacks. Among the natural polymers, chitosan and alginate have been studied extensively for preparation of hydrogel nanoparticles and from synthetic group, hydrogel nanoparticles based on poly (vinyl alcohol), poly (ethylene oxide), poly (ethyleneimine), poly (vinyl pyrrolidone), and poly-N-isopropylacrylamide have been reported with different characteristics and features with respect to drug delivery. Regardless of the type of polymer used, the release mechanism of the loaded agent from hydrogel nanoparticles is complex, while resulting from three main vectors, i.e., drug diffusion, hydrogel matrix swelling, and chemical reactivity of the drug/matrix. Several crosslinking methods have been used in the way to form the hydrogel matix structures, which can be classified in two major groups of chemically- and physically-induced crosslinking.     

Dissolution and Permeation Properties of Naproxen From Solid-State Systems With Chitosan

The purpose of this study was to investigate the influence of different types of chitosan and of the preparation technique of the drug–polymer combination in improving the dissolution and permeation abilities of naproxen, a very poorly water-soluble anti-inflammatory drug. Drug–chitosan systems were prepared by simple physical mixing, kneading, cogrinding, or coevaporation using five types of chitosan (base and glutamate or hydrochloride salts, both at two different molecular weights). The products were tested for drug-dissolution behavior and for permeation properties through both Caco-2 cell monolayers and artificial lipophilic membranes. All combinations with chitosan base were significantly (p < .01) more effective in enhancing drug-dissolution rate than those with both its salts, probably in virtue of its higher amorphizing effect toward the drug, as observed in solid-state studies. A different rank order was found in permeation experiments in which chitosan glutamate was the most powerful partner in improving the drug-apparent permeability (p < .01), followed by the hydrochloride salt (p < .05), whereas no significant effect was obtained with chitosan base. Cogrinding was the most powerful technique in promoting both dissolution and permeation properties of the drug, thus pointing out the importance of the preparation method in obtaining efficacious drug-carrier systems. Finally, the good correspondence between permeation experiments with Caco-2 cells and those with the artificial lipophilic membrane indicated the suitability of this latter in preformulation studies for a rapid screening of the best carrier and the most efficient drug-carrier preparation method for improving the biopharmaceutical properties of drugs.     

Dissolution and permeation properties of naproxen from solid-state systems with chitosan

The purpose of this study was to investigate the influence of different types of chitosan and of the preparation technique of the drug-polymer combination in improving the dissolution and permeation abilities of naproxen, a very poorly water-soluble anti-inflammatory drug. Drug-chitosan systems were prepared by simple physical mixing, kneading, cogrinding, or coevaporation using five types of chitosan (base and glutamate or hydrochloride salts, both at two different molecular weights). The products were tested for drug-dissolution behavior and for permeation properties through both Caco-2 cell monolayers and artificial lipophilic membranes. All combinations with chitosan base were significantly (p < .01) more effective in enhancing drug-dissolution rate than those with both its salts, probably in virtue of its higher amorphizing effect toward the drug, as observed in solid-state studies. A different rank order was found in permeation experiments in which chitosan glutamate was the most powerful partner in improving the drug-apparent permeability (p < .01), followed by the hydrochloride salt (p < .05), whereas no significant effect was obtained with chitosan base. Cogrinding was the most powerful technique in promoting both dissolution and permeation properties of the drug, thus pointing out the importance of the preparation method in obtaining efficacious drug-carrier systems. Finally, the good correspondence between permeation experiments with Caco-2 cells and those with the artificial lipophilic membrane indicated the suitability of this latter in preformulation studies for a rapid screening of the best carrier and the most efficient drug-carrier preparation method for improving the biopharmaceutical properties of drugs.     

肺靶向多西紫杉醇壳聚糖微球的制备与工艺优化

目的：研制肺靶向多西紫杉醇壳聚糖微球,并对处方工艺进行筛选。方法：以壳聚糖为载体,采用乳化-化学交联法制备多西紫杉醇壳聚糖微球。在单因素考察的基础上,利用正交试验设计优化微球制备工艺,采用HPLC法测定微球的载药量与包封产率。结果：制得的微球显微观察形态圆整、表面光滑,无粘连;平均粒径为（8．63±0．27）μm,粒径7—12μm的微球平均占总数的83．5％,载药量为（25．01±1．80）％,包封产率为（85．54±2．21）％。结论：筛选的最佳处方工艺制备的微球粒径大小适宜,可满足肺靶向微球的要求;该制剂有可能成为临床肺部肿瘤治疗的一种靶向制剂。     

注射用微乳的研究进展

微乳是由表面活性剂、辅助表面活性剂、油和水在适当比例下自发形成的透明或半透明分散体系.作为一种新型药物输送载体,除了具有乳剂的一般特征外,微乳还具有粒径小、可过滤灭菌、热力学稳定、黏度低、注射时刺激性小及制备简单等优点,是很多疏水性药物注射给药时的良好载体.本文主要从制备注射用微乳时考虑的各因素、微乳的评价指标,及微乳存在的一些不足等方面对注射用微乳的研究进展做一概括.     

壳聚糖纳米粒作为药物递送系统在癌症治疗中的应用

癌症是威胁人类生存的恶性疾病之一。近年来,利用纳米技术将药物靶向递送到肿瘤部位,可以增加疗效并降低毒性,为癌症治疗带来了新希望。壳聚糖是自然界唯一存在的碱性多糖,具有良好的生物相容性和生物可降解性。此外,其反应位点多,可制成不同性质的衍生物,广泛用于药物递送系统和组织工程支架,在生物医药领域具有重要的应用价值。本综述对近年来壳聚糖纳米粒在抗癌药物递送方面的研究进展进行介绍,重点介绍了壳聚糖纳米粒的制备、被动靶向、主动靶向和刺激-响应药物递送系统方面的研究进展。