Baumann Frank, Paul Theresa, Ossmann Susann, Enke Dirk, Aigner Achim
Rudolf-Boehm-Institute for Pharmacology and Toxicology, Clinical Pharmacology, Faculty of Medicine, Leipzig University, 04107 Leipzig, Germany.
Institute of Chemical Technology, Leipzig University, 04103 Leipzig, Germany.
Pharmaceutics. 2024 Jul 26;16(8):995. doi: 10.3390/pharmaceutics16080995.
Compared to other forms of drug administration, the use of Transdermal Drug Delivery Systems (TDDSs) offers significant advantages, including uniform drug release profiles that contribute to lower side effects and higher tolerability, avoidance of direct exposure to the gastrointestinal tract, better patient compliance due to their non-invasive means of application and others. Mesoporous silica membranes are of particular interest in this regard, due to their chemical stability and their tunable porous system, with adjustable pore sizes, pore volumes and surface chemistries. While this allows for fine-tuning and, thus, the development of optimized TDDSs with high loading capacities and the desired release profile of a given drug, its systemic availability also relies on skin penetration. In this paper, using a TDDS based on mesoporous silica membranes in Franz cell experiments on porcine skin, we demonstrate surprisingly substantial drug loss during skin penetration. Drug passage through porcine skin was found to be dependent on the age and pre-treatment of the skin. pH and temperature were major determinants of drug recovery rates as well, indicating drug loss in the skin by enzymatic metabolization. Regarding the TDDS, higher loading obtained by SOH surface modification of the mesoporous silica membranes reduced drug loss. Still, high loss rates in the skin were determined for different drugs, including anastrozole, xylazine and imiquimod. We conclude that, beyond the fine-tuned drug release profiles from the mesoporous silica membrane TDDS, remarkably high drug loss in the skin is a major issue for achieving desired skin penetration and, thus, the systemic availability of drugs. This also poses critical requirements for defining an optimal TDDS based on mesoporous silica membranes.
与其他药物给药形式相比，透皮给药系统（TDDS）的使用具有显著优势，包括药物释放曲线均匀，有助于降低副作用和提高耐受性，避免直接接触胃肠道，因其非侵入性的应用方式而具有更好的患者依从性等。在这方面，介孔二氧化硅膜特别受关注，因为它们具有化学稳定性和可调谐的多孔系统，其孔径、孔体积和表面化学性质均可调节。虽然这允许进行微调，从而开发出具有高载药量和给定药物所需释放曲线的优化TDDS，但其全身可用性也依赖于皮肤渗透。在本文中，我们在猪皮的Franz扩散池实验中使用基于介孔二氧化硅膜的TDDS，结果表明在皮肤渗透过程中药物损失惊人地大。发现药物通过猪皮的情况取决于皮肤的年龄和预处理。pH值和温度也是药物回收率的主要决定因素，表明药物在皮肤中因酶代谢而损失。对于TDDS，通过介孔二氧化硅膜的SOH表面改性获得的更高载药量降低了药物损失。尽管如此，对于不同药物，包括阿那曲唑、赛拉嗪和咪喹莫特，在皮肤中的损失率仍然很高。我们得出结论，除了介孔二氧化硅膜TDDS具有微调的药物释放曲线外，皮肤中极高的药物损失是实现所需皮肤渗透以及药物全身可用性的一个主要问题。这也对定义基于介孔二氧化硅膜的最佳TDDS提出了关键要求。
