Pawar Vaishali, Borse Vivek, Thakkar Riya, Srivastava Rohit
Department of Biosciences and Bioengineering, Indian Institute of Technology (IIT) Bombay, Powai, Mumbai 400076, India.
Curr Drug Deliv. 2018;15(5):716-726. doi: 10.2174/1567201814666171013151750.
In situ gel formulations have been widely reported as a carrier for sustained release delivery systems due to certain advantages such as targeted drug delivery, minimal invasiveness and potent therapeutic activity.
Herein, in situ gel system for sustained release of doxorubicin and ibuprofen for anti-cancer and anti-inflammatory activity is reported.
Doxorubicin-conjugated alginate (dox-alg) gel was prepared using EDC-NHS chemistry and loaded with ibuprofen encapsulated polycaprolactone (PCL) microparticles (dox-alg composite). PCL microparticles were prepared by a solvent evaporation method (size 50 - 100µm). The gel was characterized using SEM, FTIR, XRD and TGA analysis.
Dox-alg composite gel showed good syringeability and gel formation properties. Burst release was observed for both drugs within 24 h followed by sustained release till day 21. Doxorubicin released from composite showed considerable cytotoxic effect. Cell uptake was confirmed by confocal microscopy using MDA-MB-231 cells. Anti-inflammatory activity of ibuprofen released from composite gel was compared with the free drug. An injection of dox-alg composite gel in the tissue would fill the void created after tumor removal surgery, prevent the resuscitation of remnant cancerous cells and reduce inflammation.
Thus, the dox-alg composite gel could be a potential agent for the dual anti-cancer and anti-inflammatory therapy.
原位凝胶制剂作为一种用于缓释给药系统的载体已被广泛报道，因其具有靶向给药、微创性和强效治疗活性等优点。
本文报道了一种用于阿霉素和布洛芬缓释的原位凝胶系统，以实现抗癌和抗炎活性。
采用EDC-NHS化学法制备阿霉素共轭藻酸盐（dox-alg）凝胶，并负载包裹布洛芬的聚己内酯（PCL）微粒（dox-alg复合物）。PCL微粒通过溶剂蒸发法制备（尺寸为50 - 100μm）。使用扫描电子显微镜（SEM）、傅里叶变换红外光谱（FTIR）、X射线衍射（XRD）和热重分析（TGA）对凝胶进行表征。
dox-alg复合凝胶表现出良好的可注射性和凝胶形成特性。两种药物在24小时内均出现突释，随后持续释放至第21天。从复合物中释放的阿霉素显示出相当大的细胞毒性作用。使用MDA-MB-231细胞通过共聚焦显微镜确认了细胞摄取。将复合凝胶中释放的布洛芬的抗炎活性与游离药物进行了比较。在组织中注射dox-alg复合凝胶将填充肿瘤切除手术后形成的空隙，防止残留癌细胞复苏并减轻炎症。
因此，dox-alg复合凝胶可能是一种用于双重抗癌和抗炎治疗的潜在药物。
