Rehman Umaira, Sarfraz Rai Muhammad, Mahmood Asif, Hussain Zahid, Thu Hnin Ei, Zafar Nadiah, Ashraf Muhammad Umar, Batool Nighat
Department of Pharmaceutics, University of Sargodha, Sargodha,Pakistan.
Department of Pharmaceutics, The University of Lahore, Lahore,Pakistan.
Curr Drug Deliv. 2021;18(9):1256-1271. doi: 10.2174/1567201818666210212085912.
Despite exhibiting promising anticancer potential, the clinical significance of capecitabine (a potent prodrug of 5-fluorouracil used for the treatment of colorectal cancer) is limited owing to its acidic and enzymatic hydrolysis, lower absorption following the oral administration, poor bioavailability, short plasma half-life, and poor patient compliance.
The present study was aimed to fabricate the capecitabine as a smart pH-responsive hydrogel network to efficiently facilitate its oral delivery while shielding its stability in the gastric media.
The smart pH-sensitive HP-β-CD/agarose-g-poly(MAA) hydrogel network was developed using an aqueous free radical polymerization technique. The developed hydrogels were characterized for drug-loading efficiency, structural and compositional features, thermal stability, swelling behaviour, morphology, physical form, and release kinetics. The pH-responsive behaviour of developed hydrogels was established by conducting the swelling and release behaviour at different pH values (1.2 and 7.4), demonstrating significantly higher swelling and release at pH 7.4 as compared with pH 1.2. The capecitabine-loaded hydrogels were also screened for acute oral toxicity in animals by analysing the body weight, water and food intake, dermal toxicity, ocular toxicity, biochemical analysis, and histological examination.
The characteristic evaluations revealed that capecitabine (anticancer agent) was successfully loaded into the hydrogel network. The range of capecitabine loading was from 71.22% to 90.12%. An interesting feature of hydrogel was its pH-responsive behaviour which triggers release at basic pH (94.25%). Optimum swelling (95%)was seen at pH 7.4. Based upon regression coefficient R2(0.96 - 0.99) the best-fit model was zero-order. The extensive toxicity evaluations evidenced a good safety profile with no signs of oral, dermal, or ocular toxicities, as well as no variations in blood parameters and histology of vital organs.
Our findings conclusively evinced that the developed hydrogel exhibited excellent pharmaceutical and therapeutic potential and thus can be employed as a pH-responsive system for the controlled delivery of anticancer agents.
尽管卡培他滨（一种用于治疗结直肠癌的5-氟尿嘧啶的有效前药）展现出了有前景的抗癌潜力，但其临床意义有限，这是由于其酸性和酶促水解、口服给药后吸收较低、生物利用度差、血浆半衰期短以及患者依从性差。
本研究旨在制备卡培他滨作为一种智能pH响应水凝胶网络，以有效促进其口服给药，同时保护其在胃介质中的稳定性。
采用水相自由基聚合技术开发了智能pH敏感的HP-β-CD/琼脂糖-g-聚（甲基丙烯酸）水凝胶网络。对所开发的水凝胶进行了载药效率、结构和组成特征、热稳定性、溶胀行为、形态、物理形态和释放动力学的表征。通过在不同pH值（1.2和7.4）下进行溶胀和释放行为，确定了所开发水凝胶的pH响应行为，结果表明与pH 1.2相比，在pH 7.4时溶胀和释放明显更高。还通过分析动物的体重、水和食物摄入量、皮肤毒性、眼毒性、生化分析和组织学检查，对载有卡培他滨的水凝胶进行了急性口服毒性筛选。
特征评估表明，卡培他滨（抗癌剂）成功负载到水凝胶网络中。卡培他滨的负载范围为71.22%至90.12%。水凝胶的一个有趣特征是其pH响应行为，该行为在碱性pH下触发释放（94.25%）。在pH 7.4时观察到最佳溶胀（95%）。基于回归系数R2（0.96 - 0.99），最佳拟合模型为零级。广泛的毒性评估证明了良好的安全性，没有口服、皮肤或眼毒性的迹象，以及重要器官的血液参数和组织学没有变化。
我们的研究结果确凿地表明，所开发的水凝胶具有优异的药学和治疗潜力，因此可以用作抗癌剂控释pH响应系统。
