Dasgupta Queeny, Movva Sahitya, Chatterjee Kaushik, Madras Giridhar
Centre for Biosystems Science and Engineering, Indian Institute of Science, Bangalore, 560012, India.
Department of Chemical Engineering, Indian Institute of Science, Bangalore, 560012, India.
Int J Pharm. 2017 Aug 7;528(1-2):732-740. doi: 10.1016/j.ijpharm.2017.06.065. Epub 2017 Jun 19.
This work reports the synthesis of a novel, aspirin-loaded, linear poly (anhydride ester) and provides mechanistic insights into the release of aspirin from this polymer for anti-inflammatory activity. As compared to conventional drug delivery systems that rely on diffusion based release, incorporation of bioactives in the polymer backbone is challenging and high loading is difficult to achieve. In the present study, we exploit the pentafunctional sugar alcohol (xylitol) to provide sites for drug (aspirin) attachment at its non-terminal OH groups. The terminal OH groups are polymerized with a diacid anhydride. The hydrolysis of the anhydride and ester bonds under physiological conditions release aspirin from the matrix. The resulting poly(anhydride ester) has high drug loading (53%) and displays controlled release kinetics of aspirin. The polymer releases 8.5 % and 20%, of the loaded drug in one and four weeks, respectively and has a release rate constant of 0.0035h. The release rate is suitable for its use as an anti-inflammatory agent without being cytotoxic. The polymer exhibits good cytocompatibility and anti-inflammatory properties and may find applications as injectable or as an implantable bioactive material. The physical insights into the release mechanism can provide development of other drug loaded polymers.
本研究报告了一种新型载阿司匹林线性聚(酸酐酯)的合成,并对该聚合物释放阿司匹林以发挥抗炎活性的机制进行了深入探讨。与依赖基于扩散释放的传统药物递送系统相比,将生物活性物质掺入聚合物主链具有挑战性,且难以实现高负载量。在本研究中,我们利用五官能糖醇(木糖醇)在其非末端羟基处提供药物(阿司匹林)附着位点。末端羟基与二酸酐聚合。生理条件下酸酐键和酯键的水解使阿司匹林从基质中释放出来。所得的聚(酸酐酯)具有高药物负载量(53%),并显示出阿司匹林的控释动力学。该聚合物在一周和四周内分别释放8.5%和20%的负载药物,释放速率常数为0.0035h⁻¹。该释放速率适合其作为抗炎剂使用而无细胞毒性。该聚合物表现出良好的细胞相容性和抗炎特性,可作为可注射或可植入的生物活性材料。对释放机制的物理见解可为其他载药聚合物的开发提供参考。