Georgieva Dilyana, Alexandrova Mariela, Ivanova Sijka, Christova Darinka, Kostova Bistra
Department of Pharmaceutical Technology and Biopharmacy, Faculty of Pharmacy, Medical University of Sofia, Dunav Str. 2, 1000 Sofia, Bulgaria.
Institute of Polymers, Bulgarian Academy of Sciences, Akad. G. Bonchev Str., Bl. 103-A, 1113 Sofia, Bulgaria.
Gels. 2023 Jun 7;9(6):470. doi: 10.3390/gels9060470.
Dexamethasone (DXM) is a highly potent and long-acting synthetic glucocorticoid with anti-inflammatory, anti-allergic, and immunosuppressive effects. However, the systemic application of DXM can cause undesirable side effects: sleep disorders, nervousness, heart rhythm disorders, heart attack, and others. In the present study, multicomponent polymer networks were developed as potential new platforms for the dermal application of dexamethasone sodium phosphate (DSP). First, a copolymer network (CPN) comprising hydrophilic segments of different chemical structures was synthesized by applying redox polymerization of dimethyl acrylamide onto poly(ethylene glycol) in the presence of poly(ethylene glycol) diacrylate (PEGDA) as a crosslinker. On this basis, an interpenetrating polymer network structure (IPN) was obtained by introducing a second network of PEGDA-crosslinked poly(N-isopropylacrylamide). Multicomponent networks obtained were characterized by FTIR, TGA, and swelling kinetics in different solvents. Both CPN and IPN showed a high swelling degree in aqueous media (up to 1800 and 1200%, respectively), reaching the equilibrium swelling within 24 h. Additionally, IPN showed temperature-responsive swelling in an aqueous solution as the equilibrium swelling degree decreased considerably with an increase in the temperature. In order to evaluate the networks' potential as drug carriers, swelling in DSP aqueous solutions of varied concentration was investigated. It was established that the amount of encapsulated DSP could be easily controlled by the concentration of drug aqueous solution. In vitro DSP release was studied in buffer solution (BS) with pH 7.4 at 37 °C. The results obtained during DSP loading and release experiments proved the feasibility of the developed multicomponent hydrophilic polymer networks as effective platforms for potential dermal application.
地塞米松（DXM）是一种高效长效的合成糖皮质激素，具有抗炎、抗过敏和免疫抑制作用。然而，DXM的全身应用会导致不良副作用：睡眠障碍、紧张、心律紊乱、心脏病发作等。在本研究中，开发了多组分聚合物网络作为地塞米松磷酸钠（DSP）皮肤应用的潜在新平台。首先，在聚乙二醇二丙烯酸酯（PEGDA）作为交联剂的存在下，通过将二甲基丙烯酰胺在聚乙二醇上进行氧化还原聚合，合成了包含不同化学结构亲水性链段的共聚物网络（CPN）。在此基础上，通过引入PEGDA交联的聚（N-异丙基丙烯酰胺）第二网络，获得了互穿聚合物网络结构（IPN）。通过FTIR、TGA和在不同溶剂中的溶胀动力学对所得多组分网络进行了表征。CPN和IPN在水性介质中均表现出高溶胀度（分别高达1800%和1200%），在24小时内达到平衡溶胀。此外，IPN在水溶液中表现出温度响应性溶胀，因为平衡溶胀度随温度升高而显著降低。为了评估网络作为药物载体的潜力，研究了在不同浓度DSP水溶液中的溶胀情况。结果表明，包封的DSP量可以通过药物水溶液的浓度轻松控制。在37℃、pH 7.4的缓冲溶液（BS）中研究了DSP的体外释放。在DSP负载和释放实验中获得的结果证明了所开发的多组分亲水性聚合物网络作为潜在皮肤应用有效平台的可行性。
