Shahid Mehreen, Zaman Muhammad, Siddique Waqar, Aman Waqar, Salawi Ahmad, Almoshari Yosif, Alamoudi Jawaher Abdullah
Faculty of Pharmacy, University of Central Punjab, Lahore 54000, Pakistan.
Riphah Institute of Pharmaceutical Sciences, Riphah International University, Lahore 54000, Pakistan.
ACS Omega. 2025 Aug 21;10(34):38555-38568. doi: 10.1021/acsomega.5c02881. eCollection 2025 Sep 2.
Tacrolimus belongs to the BCS class-II drug family and exhibits poor water solubility, which leads to poor bioavailability. Furthermore, since tacrolimus is an immunosuppressant, it is essential to maintain its therapeutic concentration for a greater period of time to confirm its effectiveness against transplant rejection. Therefore, to achieve the objective of the sustained release of the drug with a suitable amount of entrapment efficiency, pH-sensitive tacrolimus-loaded superabsorbent hydrogels using chitosan have been prepared. The free-radical polymerization technique has been used to develop the hydrogel formulation, where chitosan served as the polymer, acrylamide served as the monomer, -methylenebis-(acrylamide) served as the cross-linker, and potassium persulfate served as the initiator. The prepared formulations were evaluated for their swelling behavior, entrapment efficiency, porosity, drug release, and kinetics. The formulation design and optimization have been carried out using a statistical tool, i.e., Design Expert. A good swelling capacity and porosity of the hydrogel have been observed, advocating a well-interconnected network structure suitable for drug entrapment and release. The porosity of the prepared hydrogel was found to be 77.7-232.16%, while the sol-gel fraction ranged between 4.65 and 17.71 and 82.29 and 95.35%, respectively. Furthermore, the release of 59.9% of the drug over 8 h of the studies has assured a good sustained behavior of the formulation. The outcomes of the studies have been advocating the successful execution of the research work, where the prepared hydrogel has demonstrated a good entrapment efficiency, followed by a suitable sustained-release behavior. Conclusively, the selected combination of the drug and excipients, the adopted method of hydrogel preparation, and the evaluation process were quite efficient for the delivery of a drug like tacrolimus.
他克莫司属于生物药剂学分类系统（BCS）中的II类药物家族，水溶性差，导致生物利用度低。此外，由于他克莫司是一种免疫抑制剂，必须在较长时间内维持其治疗浓度，以确认其对移植排斥反应的有效性。因此，为了实现药物的持续释放并达到合适的包封率，制备了使用壳聚糖的pH敏感型载他克莫司超吸水性水凝胶。采用自由基聚合技术开发水凝胶制剂，其中壳聚糖作为聚合物，丙烯酰胺作为单体，N,N'-亚甲基双丙烯酰胺作为交联剂，过硫酸钾作为引发剂。对制备的制剂进行了溶胀行为、包封率、孔隙率、药物释放和动力学评估。使用统计工具Design Expert进行了制剂设计和优化。观察到水凝胶具有良好的溶胀能力和孔隙率，表明其网络结构相互连通良好，适合药物包封和释放。制备的水凝胶孔隙率为77.7 - 232.16%，溶胶-凝胶分数分别在4.65至17.71以及82.29至95.35之间。此外，在8小时的研究中药物释放率达至59.9%，确保了制剂具有良好的持续释放性能。研究结果表明该研究工作成功实施，所制备的水凝胶显示出良好的包封率，随后具有合适的持续释放行为。总之，所选药物与辅料的组合、所采用的水凝胶制备方法以及评估过程对于递送他克莫司这类药物相当有效。
