Simeonov Marin, Kostova Bistra, Mihaylova Rositsa, Vassileva Elena
Laboratory on Structure and Properties of Polymers, Faculty of Chemistry and Pharmacy, University of Sofia, 1, J. Bourchier Blvd., 1164 Sofia, Bulgaria.
Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, Medical University of Sofia, 2, Dunav Str., 1000 Sofia, Bulgaria.
Pharmaceutics. 2025 Jan 5;17(1):62. doi: 10.3390/pharmaceutics17010062.
: This study is an attempt to reveal the potential of two types of interpenetrating polymer network (IPN) hydrogels based on poly(2-hydroxyethyl methacrylate) (PHEMA) and poly(N,N-dimethylacrylamide) (PDMAM). These IPNs were evaluated for their potential for dermal delivery of the hydrophobic drug dexamethasone (DEX). : The two types of IPNs were analyzed for their rheological behavior, swelling characteristics, and drug-loading capacity with DEX. Drug release profiles were studied in Franz diffusion cells in PBS media. Finally, the cytotoxicity of the PHEMA/PDMAM-based IPNs was studied against T-cell lymphoma cells (HUT-78) and a normal murine fibroblast cell line (CCL-1). : The rheological properties of these hydrogels show suitable mechanical properties for dermal application, with G' values of 10 kPa. From the rheological data, the mesh size of these hydrogels was found to be influenced by the type of the IPN and its composition, varying between 6.5 and 50 nm. The loading capacity of both IPN types and DEX entrapment efficiency were highly influenced by the IPN's composition. The loading capacity of the IPNs can reach ~3.5%, with a DEX entrapment efficiency of ~35%. The PHEMA/PDMAM IPNs demonstrate an extended release profile with up to ~95% DEX released in 24 h, while PDMAM/PHEMA IPNs release no more than ~25% DEX in 24 h. The drug release profiles follow either non-Fickian diffusion (n0.6) or case-II transport (n~0.9-1), depending on the IPN's composition. The PHEMA/PDMAM-based materials were found to be non-cytotoxic against HUT-78 and CCL-1 cells. : The study reveals that the IPNs of PHEMA and PDMAM appear to be suitable platforms for dermal delivery of dexamethasone as they have appropriate mechanical properties, providing tools to control drug loading and release, and they are biocompatible with human skin cells.
本研究旨在揭示基于聚甲基丙烯酸2-羟乙酯（PHEMA）和聚N,N-二甲基丙烯酰胺（PDMAM）的两种互穿聚合物网络（IPN）水凝胶的潜力。对这些IPN进行评估，以确定其用于疏水性药物地塞米松（DEX）经皮给药的潜力。分析了这两种类型的IPN的流变行为、溶胀特性以及对DEX的载药能力。在PBS介质中的Franz扩散池中研究了药物释放曲线。最后，研究了基于PHEMA/PDMAM的IPN对T细胞淋巴瘤细胞（HUT-78）和正常小鼠成纤维细胞系（CCL-1）的细胞毒性。这些水凝胶的流变特性显示出适合经皮应用的机械性能，储能模量（G'）值约为10 kPa。从流变数据可知，这些水凝胶的网孔尺寸受IPN类型及其组成的影响，在6.5至50 nm之间变化。两种IPN类型的载药能力和DEX包封效率都受到IPN组成的高度影响。IPN的载药能力可达约3.5%，DEX包封效率约为35%。PHEMA/PDMAM IPN呈现出缓释曲线，在24小时内DEX释放量高达约95%，而PDMAM/PHEMA IPN在24小时内DEX释放量不超过约25%。药物释放曲线遵循非菲克扩散（n≈0.6）或第二类转运（n≈0.9 - 1），具体取决于IPN的组成。发现基于PHEMA/PDMAM的材料对HUT-78和CCL-1细胞无细胞毒性。该研究表明，PHEMA和PDMAM的IPN似乎是地塞米松经皮给药的合适平台，因为它们具有适当的机械性能，提供了控制药物负载和释放的手段，并且与人类皮肤细胞具有生物相容性。
