Senarat Setthapong, Pornsawad Pornsarp, Lertsuphotvanit Nutdanai, Østergaard Jesper, Phaechamud Thawatchai
Programme of Pharmaceutical Engineering, Faculty of Pharmacy, Silpakorn University, Nakhon Pathom 73000, Thailand.
Department of Mathematics, Faculty of Science, Silpakorn University, Nakhon Pathom 73000, Thailand.
Pharmaceutics. 2023 Sep 28;15(10):2401. doi: 10.3390/pharmaceutics15102401.
The development of effective drug delivery systems remains a focus of extensive research to enhance therapeutic outcomes. Among these, in situ forming gels (ISG) have emerged as a promising avenue for controlled drug release. This research focuses on the mathematical modeling of levofloxacin HCl (Lv) release from zein-based ISG using the cup method, aiming to mimic the environment of a periodontal pocket. The drug release behavior of the ISGs was investigated through experimental observations and numerical simulations employing forward and central difference formula. Notably, the experimental data for drug release from the 20% / zein-based ISG formulations closely aligned with the simulations obtained from numerical mechanistic modeling. In summary, 20% / zein-based ISG formulations demonstrated nearly complete drug release with the maximum drug concentration at the edge of the matrix phase values consistently around 100-105%, while 25% / zein-based ISG formulations exhibited somewhat lower drug release extents, with values ranging from 70-90%. Additionally, the rate of drug transport from the polymer matrix to the external phase influenced initial release rates, resulting in a slower release. The utilization of glycerol formal as a solvent extended drug release further than dimethyl sulfoxide, thanks to denser matrices formed by high-loading polymers that acted as robust barriers to solvent removal and drug diffusion. Furthermore, UV-vis imaging was utilized to visualize the matrix formation process and solvent diffusion within the ISGs. The imaging results offered valuable insights into the matrix formation kinetics, controlled drug release mechanisms, and the influence of solvent properties on drug diffusion. The combination of mathematical modeling and experimental visualization provides a comprehensive understanding of drug release from zein-based ISGs and offers a foundation for tailored drug delivery strategies.
开发有效的药物递送系统仍然是广泛研究的重点，以提高治疗效果。其中，原位形成凝胶（ISG）已成为控制药物释放的一个有前景的途径。本研究聚焦于使用杯法对盐酸左氧氟沙星（Lv）从玉米醇溶蛋白基ISG中的释放进行数学建模，旨在模拟牙周袋的环境。通过实验观察和采用前向和中心差分公式的数值模拟，研究了ISG的药物释放行为。值得注意的是，20%玉米醇溶蛋白基ISG制剂的药物释放实验数据与数值机理建模得到的模拟结果紧密吻合。总之，20%玉米醇溶蛋白基ISG制剂显示出几乎完全的药物释放，基质相边缘的最大药物浓度值始终在100 - 105%左右，而25%玉米醇溶蛋白基ISG制剂的药物释放程度略低，值在70 - 90%之间。此外，药物从聚合物基质向外相的传输速率影响初始释放速率，导致释放较慢。使用甲醛甘油作为溶剂比二甲基亚砜进一步延长了药物释放，这得益于高负载聚合物形成的更致密的基质，这些基质对溶剂去除和药物扩散起到了强大的屏障作用。此外，利用紫外 - 可见成像来可视化ISG内的基质形成过程和溶剂扩散。成像结果为基质形成动力学、控制药物释放机制以及溶剂性质对药物扩散的影响提供了有价值的见解。数学建模与实验可视化的结合提供了对玉米醇溶蛋白基ISG药物释放的全面理解，并为定制药物递送策略奠定了基础。
