Thermoreversible Pluronic® F127-based hydrogel containing liposomes for the controlled delivery of paclitaxel: in vitro drug release, cell cytotoxicity, and uptake studies
Thermoreversible Pluronic® F127-based hydrogel containing liposomes for the controlled delivery of paclitaxel: in vitro drug release, cell cytotoxicity, and uptake studies
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DOI：
10.2147/ijn.s15057
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发表时间：
2011-01-01
影响因子：
8
通讯作者：
Yang, Zhijun
中科院分区：
文献类型：
--
作者：
Nie, Shufang;Hsiao, W. L. Wendy;Yang, Zhijun
目的：开发一种将含有紫杉醇（PTX）的脂质体分散在热可逆凝胶（Pluronic（R）F127凝胶）中的原位凝胶系统，用于控制释放并提高抗肿瘤药物效率。方法：采用透析膜和无膜扩散法研究体外药物释放行为。差示扫描量热法（DSC）热分析用于研究原位凝胶体系的“胶束化”和“溶胶/凝胶转变”过程。通过MTT、细胞间药物浓度和荧光强度测定测定KB癌细胞的体外细胞毒性和药物摄取。结果：用透析膜模型进行的体外释放实验表明，与脂质体、普通凝胶和商品制剂紫杉醇（R）相比，脂质体凝胶表现出最长的药物释放期。这种效应可能是由于脂质体凝胶粘度增加，从而产生药物储库的作用。原位凝胶系统的药物和凝胶释放均在零级动力学下运行，并显示出 PTX 与凝胶释放的相关性，表明侵蚀类型的主要释放机制。将脂质体分散到凝胶中取代了更大的凝胶本身，以获得相同的凝胶溶解速率。通过 DSC 热分析检测到的临界胶束温度和溶胶/凝胶温度都通过添加脂质体转移到较低的温度。变化的程度取决于嵌入的脂质体的量。 MTT测定和药物摄取研究表明，负载PTX的脂质体18% Pluronic F127处理产生的细胞毒性、细胞间荧光强度和KB细胞中的药物浓度远高于传统脂质体，而空白脂质体18% Pluronic F127凝胶远低于Cremophor EL(R)载体和空载剂。 结论：嵌入脂质体的热敏水凝胶是一种有前景的疏水性抗癌药物载体，可用于治疗局部癌症的胃肠外制剂。
Purpose: To develop an in situ gel system comprising liposome-containing paclitaxel (PTX) dispersed within the thermoreversible gel (Pluronic (R) F127 gel) for controlled release and improved antitumor drug efficiency.Methods: The dialysis membrane and membrane-less diffusion method were used to investigate the in vitro drug release behavior. Differential scanning calorimetry (DSC) thermal analysis was used to investigate the "micellization" and "sol/gel transition" process of in situ gel systems. In vitro cytotoxicity and drug uptake in KB cancer cells were determined by MTT, intercellular drug concentration, and fluorescence intensity assay.Results: The in vitro release experiment performed with a dialysis membrane model showed that the liposomal gel exhibited the longest drug-release period compared with liposome, general gel, and commercial formulation Taxol (R). This effect is presumably due to the increased viscosity of liposomal gel, which has the effect of creating a drug reservoir. Both drug and gel release from the in situ gel system operated under zero-order kinetics and showed a correlation of release of PTX with gel, indicating a predominating release mechanism of the erosion type. Dispersing liposomes into the gel replaced larger gel itself for achieving the same gel dissolution rate. Both the critical micelle temperature and the sol/gel temperature, detected by DSC thermal analysis, were shifted to lower temperatures by adding liposomes. The extent of the shifts depended on the amount of embedded liposomes. MTT assay and drug uptake studies showed that the treatment with PTX-loaded liposomal 18% Pluronic F127 yielded cytotoxicities, intercellular fluorescence intensity, and drug concentration in KB cells much higher than that of conventional liposome, while blank liposomal 18% Pluronic F127 gel was far less than the Cremophor EL (R) vehicle and empty liposomes.Conclusions: A thermosensitive hydrogel with embedded liposome is a promising carrier for hydrophobic anticancer agents, to be used in parenteral formulations for treating local cancers.