The use of colloidal microgels as a (trans)dermal drug delivery system
The use of colloidal microgels as a (trans)dermal drug delivery system
复制标题
DOI：
10.1016/j.ijpharm.2004.11.040
复制
发表时间：
2005-03-23
影响因子：
5.8
通讯作者：
Snowden, MJ
中科院分区：
文献类型：
--
作者：
Lopez, VC;Hadgraft, J;Snowden, MJ
合成了一种由聚n -异丙基丙烯酰胺（85%）、共丙烯酸丁酯（10%）、共甲基丙烯酸（5%）（NIPAM/BA/MAA）（85/10/5）组成的微凝胶，并对其作为一种潜在的pH和温度敏感透皮给药装置进行了研究。将三种不同辛醇/水分配系数和溶解度的化合物掺入微凝胶中，分别是：水杨酰胺（SA）、对羟基苯甲酸甲酯（MP）和对羟基苯甲酸丙酯（PP）。这些微凝胶-药物复合物的理化性质表明，与单独的共聚合物NIPAM/BA/MAA（85/10/5）相比，加入NIP和SA的微凝胶在改变环境pH或温度后体积更小。这种体积的减小可归因于化合物与微凝胶颗粒的结合，对网络中存在的带电基团具有屏蔽作用。在305 K、pH 3-7范围内对SA、NIP和PP的饱和溶液以及含有这三种化合物的微凝胶颗粒进行了人体皮肤的扩散研究。与饱和溶液相比，掺入NIP的微凝胶的传输速率降低了2/3倍，掺入PP的微凝胶的传输速率降低了一个数量级，同时掺入SA的微凝胶的传输速率与相应的饱和溶液的传输速率相同。饱和胶体分散体的透皮释放研究表明，pH对药物释放的控制是边际的。化合物在pH/温度敏感共聚物NIPAM/BA/MAA（85/10/5）中的掺入和随后的释放取决于各自化合物的辛醇/水分配系数和溶解度。(c) 2004 Elsevier B.V.版权所有
A co-polymer of poly(N-isopropylacrylamide) (85%) co-butyl acrylate (10%) co-methacrylic acid (5%) (NIPAM/BA/MAA) (85/10/5) microgel was synthesised and investigated as a potential pH and temperature sensitive transdermal delivery device. Three compounds having different octanol/water partition coefficients and solubilities were incorporated into the microgel, namely: salicylamide (SA), methyl paraben (MP) and propyl paraben (PP). Physico-chemical characterisation of these microgel-drug complexes showed that microgels incorporating NIP and SA have smaller volumes after changing environmental pH or temperature when compared with the co-polymer NIPAM/BA/MAA (85/10/5) alone. This reduction in volume could be attributed to the incorporation of the compounds into the microgel particles, having a shielding effect on the charged groups present within the network. Diffusion studies, across human skin, were performed at 305 K in the range of pH 3-7 for saturated solutions of SA, NIP and PP, and for microgel particles incorporating the three compounds. The transport rate for these microgels incorporating NIP was reduced by 2/3-fold compared to the saturated solution, by one order of magnitude for PP, meanwhile the transport rate for these microgels incorporating SA is the same order of magnitude as that for the corresponding saturated solutions. Transdermal release studies of the saturated colloidal dispersions indicated that pH control of the drug release was marginal. The incorporation of compounds into the pH/temperature sensitive co-polymer NIPAM/BA/MAA (85/10/5) and the subsequent release depends on the octanol/water partition coefficient and solubility of the respective compound. (c) 2004 Elsevier B.V. All rights reserved.