Hsu Wei-Chin, Hu Teh-Min
Department of Pharmacy, College of Pharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan.
ACS Omega. 2025 Aug 13;10(33):37639-37649. doi: 10.1021/acsomega.5c04153. eCollection 2025 Aug 26.
Gastroretentive drug delivery systems (GRDDS) are attractive oral extended-release dosage forms that prolong drug release and absorption in the gastrointestinal tract through engineered mechanisms to extend the residence time of orally administered dosage forms in the stomach. One of the gastroretentive designs is to render the dosage forms floatable in the gastric fluid upon oral administration. The present study aimed to develop albumin cryogels with extended buoyancy and remarkable resistance to gastric proteolysis. Protein hydrogel monoliths can be prepared through thiol-organosilane-mediated hydrogelation of bovine serum albumin, followed by lyophilization to remove water, thereby producing cryogels. The study demonstrates that, by adjusting the composition of NaHPO and sodium alginate in the hydrogel formulation, protein degradability can be effectively tuned to produce an intact floating structure with sustained buoyancy for over 24 h in simulated gastric fluid. This result is consistent with the finding that fluorescein, as a model payload, generally exhibited a decreased release rate from the formulations with increasing concentrations of NaHPO and alginate. Notably, above a threshold concentration (i.e., about 2%) of alginate, the hydrogel monolith rapidly disintegrated in nearly neutral environments such as water and simulated intestinal fluid, exhibiting pH-responsive characteristics. Finally, the generalizability of the albumin-organosilane-alginate system as a promising controlled-release platform is further demonstrated in expanded application examples, using doxorubicin, mitoxantrone, methylene blue, and rhodamine 6G as the loaded payload; all exhibiting reproducible controlled-release profiles for the alginate-doped formulation. This finding can be explained by the SEM images showing smaller and denser porous structures with thicker, fiber-tangled intercompartment walls for gels with high alginate concentrations. Overall, the freeze-dried albumin-organosilane-alginate cryogel formulation demonstrates excellent buoyancy, resistance to degradation by simulated gastric fluid, and the ability to regulate drug release, highlighting its feasibility as a GRDDS.
胃滞留型药物递送系统（GRDDS）是一种具有吸引力的口服缓释剂型，它通过工程化机制延长药物在胃肠道中的释放和吸收，从而延长口服剂型在胃中的停留时间。胃滞留设计之一是使剂型在口服后能在胃液中漂浮。本研究旨在开发具有延长浮力和显著抗胃蛋白酶水解能力的白蛋白冷冻凝胶。蛋白质水凝胶整体可以通过牛血清白蛋白的硫醇 - 有机硅烷介导的水凝胶化制备，然后通过冻干去除水分，从而制备冷冻凝胶。该研究表明，通过调整水凝胶配方中NaHPO和海藻酸钠的组成，可以有效调节蛋白质的降解性，以产生完整的漂浮结构，并在模拟胃液中保持超过24小时的持续浮力。这一结果与以下发现一致：作为模型载药量的荧光素，通常随着NaHPO和海藻酸钠浓度的增加，其从制剂中的释放速率降低。值得注意的是，当海藻酸钠浓度高于阈值浓度（即约2%）时，水凝胶整体在接近中性的环境（如水和模拟肠液）中迅速崩解，表现出pH响应特性。最后，使用阿霉素、米托蒽醌、亚甲蓝和罗丹明6G作为负载药物，在扩展的应用实例中进一步证明了白蛋白 - 有机硅烷 - 海藻酸盐系统作为一种有前景的控释平台的通用性；所有海藻酸盐掺杂制剂均表现出可重复的控释曲线。这一发现可以通过扫描电子显微镜图像来解释，该图像显示，对于高海藻酸钠浓度的凝胶，其具有更小、更致密的多孔结构以及更厚、纤维缠结的隔室壁。总体而言，冻干的白蛋白 - 有机硅烷 - 海藻酸盐冷冻凝胶制剂表现出优异的浮力、抗模拟胃液降解能力以及调节药物释放的能力，突出了其作为胃滞留型药物递送系统的可行性。
