Jitrangsri Kritamorn, Khaing Ei Mon, Intaraphairot Torsak, Phaechamud Thawatchai, Mahadlek Jongjan
Department of Chemical Engineering and Pharmaceutical Chemistry, School of Engineering and Technology, Walailak University, Nakhon Srithammarat 80160, Thailand.
Natural Bioactive and Material for Health Promotion and Drug Delivery System Group (NBM Group), Faculty of Pharmacy, Silpakorn University, Nakhon Pathom 73000, Thailand.
Gels. 2023 Sep 12;9(9):737. doi: 10.3390/gels9090737.
The aim of this study was to prepare and characterize the imatinib mesylate (IM)-loaded gamboge-based ISG system for local administration of an anticancer agent against colorectal carcinoma. The ISG formulations were prepared in dimethyl sulfoxide (DMSO) and -methyl-2-pyrrolidone (NMP). The physicochemical properties, drug release profile, and cytotoxicity of the developed formulations were assessed. The developed ISG demonstrated Newtonian flow behavior with acceptable rheological and mechanical properties. The viscosity of the developed ISG, measured at less than 80 cP, and the applied forces of less than 50 N·mm, indicated easy administration using clinical injection techniques. Upon contact with an aqueous phase, the ISG immediately formed a porous cross-sectional structure, enabling sustained release of IM over 14 days. The release profile of IM was fitted to the quasi-Fickian diffusion mechanism, and the release rate could be controlled by the types of solvent and the amount of IM content. The developed IM-loaded gamboge ISG effectively inhibited colorectal cancer cells, including HCT116 and HT29 cell lines, with less than 20% cell viability observed at a concentration of 1% / IM after 2 days of incubation. This suggests that the developed ISG may potentially serve as an injectable system for localized anticancer delivery against colorectal cells, potentially reducing the side effects of systemic chemotherapy and improving patient adherence.
本研究的目的是制备并表征负载甲磺酸伊马替尼（IM）的藤黄基原位凝胶系统，用于局部给药抗癌剂以治疗结直肠癌。原位凝胶制剂在二甲基亚砜（DMSO）和N-甲基-2-吡咯烷酮（NMP）中制备。评估了所开发制剂的物理化学性质、药物释放曲线和细胞毒性。所开发的原位凝胶表现出牛顿流体行为，具有可接受的流变学和机械性能。所开发的原位凝胶在低于80厘泊的粘度和低于50 N·mm的作用力下，表明使用临床注射技术易于给药。与水相接触后，原位凝胶立即形成多孔横截面结构，使IM能够在14天内持续释放。IM的释放曲线符合准菲克扩散机制，释放速率可通过溶剂类型和IM含量来控制。所开发的负载IM的藤黄原位凝胶有效抑制了包括HCT116和HT29细胞系在内的结肠癌细胞，孵育2天后，在1%/IM浓度下观察到细胞活力低于20%。这表明所开发的原位凝胶可能潜在地作为一种可注射系统，用于针对结肠细胞的局部抗癌递送，有可能减少全身化疗的副作用并提高患者依从性。
