Polymeric Materials Group for the Controlled Release of Bioactive Compounds in Biomedicine, Biochemistry and Molecular Biology Department, Facultad de Medicina, Universidad Complutense de Madrid, Madrid 28040, Spain.
Nursing Department, Facultad de Enfermería, Universidad Complutense de Madrid, Madrid 28040, Spain.
Int J Pharm. 2014 Aug 15;470(1-2):107-19. doi: 10.1016/j.ijpharm.2014.05.002. Epub 2014 May 9.
Environmentally sensitive hydrogels have gained considerable attention in recent years as one of the most promising drug delivery systems. In the present study, two new formulations of pH and temperature stimuli-responsive nanogels (NGs) based on poly-N-isopropylacrylamide (NIPA), N-hydroxyethyl acrylamide (HEAA) and tert-butyl 2-acrylamidoethyl carbamate (2AAECM) were synthesized and evaluated for passive targeting of paclitaxel (PTX). Nanogels were prepared by microemulsion polymerization method using N-methylenebis(acrylamide) (NMBA) as crosslinking agent. TEM images and DLS results showed nanosized spherical hydrogels. FTIR spectra confirmed the synthesis of nanogels by radical polymerization among vinyl groups of monomers. The PTX loading capacity, encapsulation efficiency and in vitro release were analyzed by HPLC. The cumulative release profile of the PTX-loaded nanohydrogels within 144h showed a faster drug release at acid pH (pH 5), similar to those observed at lysosome compartment, whereas a fewer PTX amount was released from NGs at pH similar to plasma levels. Cellular uptake assays revealed rapid penetration and intracellular accumulation of those nanogels in MCF7, HeLa and T47D cells after 48h incubation. MTT assays showed cell viability dependence on concentration and time incubation. Finally, the PTX effect on cell viability showed a G2/M cell arrest after using PTX-loaded NGs and pure PTX.
近年来，环境敏感水凝胶作为最有前途的药物传递系统之一受到了广泛关注。在本研究中，合成了两种基于聚 N-异丙基丙烯酰胺（NIPA）、N-羟乙基丙烯酰胺（HEAA）和叔丁基 2-丙烯酰胺乙基碳酸酯（2AAECM）的新型 pH 和温度刺激响应纳米凝胶（NGs）配方，并对其进行了紫杉醇（PTX）的被动靶向评价。纳米凝胶通过使用 N-亚甲基双丙烯酰胺（NMBA）作为交联剂的微乳液聚合方法制备。TEM 图像和 DLS 结果表明纳米凝胶为纳米尺寸的球形水凝胶。FTIR 光谱证实了通过单体中乙烯基之间的自由基聚合合成了纳米凝胶。通过 HPLC 分析了 PTX 的载药量、包封效率和体外释放。在 144 小时内，载有 PTX 的纳米水凝胶的累积释放曲线显示在酸性 pH（pH 5）下药物释放更快，类似于溶酶体隔室中观察到的情况，而在与血浆水平相似的 pH 下，NGs 释放的 PTX 量较少。细胞摄取实验表明，在孵育 48 小时后，这些纳米凝胶在 MCF7、HeLa 和 T47D 细胞中迅速穿透并在细胞内积累。MTT 分析表明细胞活力取决于浓度和时间孵育。最后，使用载有 PTX 的 NGs 和纯 PTX 后，PTX 对细胞活力的影响显示 G2/M 细胞停滞。
