Abstract：
Purpose of this study was to prepare chitosan/tamarind crosslinked poly (methacrylic acid) hydrogels for pH responsive delivery of cytarabine by using aqueous free radical polymerization technique. Polymers were chemically cross-linked with monomer (methacrylic acid) using methylene bisacrylamide as cross-linking agent and ammonium per sulphate as a reaction initiator in aqueous medium. Developed hydrogels were characterized for morphology, physical existence, drug loading (%), compositional and structural analysis, thermal behavior and stability, drug release analysis (pH 1.2 and pH 7.4), and in vivo release kinetics. pH sensitive behavior was established by observing swelling and release behavior at different pH values (1.2 and 7.4). Biocompatibility of network was evaluated through acute oral toxicity studies in rabbits. Results revealed that cytarabine was efficiently loaded in prepared hydrogels with an entrapment efficiency of 54.67%-108.59%. Highest swelling ratio of 38.67 was noticed at pH 7.4. Maximum pH sensitive behavior was seen at pH 7.4 showing maximum drug release up to 94.51%. All developed formulations followed zero order release as confirmed from regression coefficient (R2 = 0.9912-0.9991). In-vivo studies confirmed enhanced bioavailability of cytarabine. Histopathological examination and hemocompatibility studies proved that developed hydrogel system was safe, biocompatible, nonhemolytic in nature exhibiting no symptoms of dermal, ocular toxicities, and no changes in biochemical parameters of blood and histology of key organs. So, developed hydrogel system can be employed as an excellent drug delivery device where controlled drug delivery is desired.
摘要：
本研究的目的是通过使用水性自由基聚合技术制备壳聚糖/罗望子交联聚（甲基丙烯酸）水凝胶，用于pH响应性递送阿糖胞苷。在水性介质中，使用亚甲基双丙烯酰胺作为交联剂，并使用过硫酸铵作为反应引发剂，将聚合物与单体（甲基丙烯酸）化学交联。开发的水凝胶的形态特征，物理存在,载药量（%），成分和结构分析，热行为和稳定性，药物释放分析（pH1.2和pH7.4），和体内释放动力学。通过在不同pH值(1.2和7.4)下观察溶胀和释放行为建立pH敏感行为。通过兔的急性口服毒性研究评估了网络的生物相容性。结果表明，阿糖胞苷有效地负载在制备的水凝胶中，包封率为54.67％-108.59％。在pH7.4时观察到最高的溶胀率38.67。在pH7.4时观察到最大的pH敏感行为，显示最大的药物释放高达94.51％。从回归系数(R2=0.9912-0.9991)证实,所有开发的制剂都遵循零级释放。体内研究证实阿糖胞苷的生物利用度提高。组织病理学检查和血液相容性研究证明，开发的水凝胶系统是安全的，生物相容性非溶血性质，没有皮肤症状，眼部毒性，血液生化参数和关键器官的组织学没有变化。所以,开发的水凝胶系统可以用作需要受控药物递送的优异的药物递送装置。
