Department of Chemistry, Kırıkkale University, Kırıkkale, Turkey.
Eur J Pharm Biopharm. 2012 Oct;82(2):316-31. doi: 10.1016/j.ejpb.2012.07.015. Epub 2012 Aug 10.
The first decade of the 21st century saw an increasing interest in the development of devices and biomaterials for delivery of bioactive substances that can be controlled by external stimuli. This study deals with the production of novel pH and temperature responsive beads for colon-specific delivery of indomethacine (IM). For this purpose, N-isopropylacrylamide (NIPAAm) was grafted onto sodium alginate (NaAlg) with microwave radiation in aqueous solution. The graft copolymer (NaAlg-g-PNIPAAm) was characterized by using attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), elemental analysis, differential scanning calorimetry (DSC), and thermogravimetric analysis. A series of pH- and temperature-responsive NaAlg-g-PNIPAAm beads were prepared as drug delivery matrices of indomethacine cross-linked by glutaraldehyde (GA) in the hydrochloric acid catalyst. Preparation condition of the beads was optimized by considering the percentage entrapment efficiency, particle size, swelling capacity of beads, and their release data. Effects of variables such as graft yield, drug/polymer ratio, exposure time to GA, and concentration of GA on the release of IM were investigated and discussed at two different pH values (1.2 and 7.4) and temperatures (25°C and 37°C). It was observed that IM release from the beads decreased when the grafting of NIPAAm, drug/polymer ratio (d/p), and extent of cross-linking were increased. The results also showed that NaAlg-g-PIPAAm beads were positive pH and temperature responsive. The release of IM from grafted beads was slower for the pH 1.2 solution than that of the pH 7.4 buffer solution, whereas the release rate was higher at 37°C than at 25°C.
21 世纪的第一个十年，人们对开发可受外部刺激控制的生物活性物质输送的装置和生物材料越来越感兴趣。本研究涉及新型 pH 和温度响应珠的制备，用于吲哚美辛（IM）的结肠特异性输送。为此，在水溶液中用微波辐射将 N-异丙基丙烯酰胺（NIPAAm）接枝到海藻酸钠（NaAlg）上。使用衰减全反射傅里叶变换红外光谱（ATR-FTIR）、元素分析、差示扫描量热法（DSC）和热重分析对接枝共聚物（NaAlg-g-PNIPAAm）进行了表征。在盐酸催化剂中用过氧化戊二醛（GA）交联，制备了一系列 pH 和温度响应的 NaAlg-g-PNIPAAm 珠作为吲哚美辛的药物输送基质。通过考虑包封效率、粒径、珠的溶胀能力及其释放数据，优化了珠的制备条件。研究并讨论了接枝产率、药物/聚合物比、GA 暴露时间和 GA 浓度等变量对 IM 释放的影响，在两个不同的 pH 值（1.2 和 7.4）和温度（25°C 和 37°C）下进行了研究。结果表明，随着 NIPAAm 的接枝、药物/聚合物比（d/p）和交联程度的增加，IM 从珠中的释放减少。结果还表明，NaAlg-g-PIPAAm 珠对 pH 和温度具有正响应性。在 pH 1.2 溶液中，IM 从接枝珠中的释放速度比在 pH 7.4 缓冲溶液中慢，而在 37°C 时的释放速度比在 25°C 时高。
