Eltabeeb Moaz A, Hamed Raghda Rabe, El-Nabarawi Mohamed A, Teaima Mahmoud H, Hamed Mohammed I A, Darwish Khaled M, Hassan Mariam, Abdellatif Menna M
Department of Industrial Pharmacy, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, Giza, Egypt.
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Drug Deliv Transl Res. 2025 Feb;15(2):556-576. doi: 10.1007/s13346-024-01611-z. Epub 2024 May 18.
Nanocomposite alginate hydrogel containing Propranolol hydrochloride (PNL) cerosomes (CERs) was prepared as a repurposed remedy for topical skin Methicillin-Resistant Staphylococcus aureus (MRSA) infection. CERs were formed via an ethanol injection technique using different ceramides, Kolliphores as a surfactant, and Didodecyldimethylammonium bromide (DDAB) as a positive charge inducer. CERs were optimized utilizing 1. 2 mixed-factorial design employing Design-Expert software, the assessed responses were entrapment efficiency (EE%), particle size (PS), and zeta potential (ZP). The optimum CER, composed of 5 mg DDAB, ceramide VI, and Kolliphor RH40 showed tubular vesicles with EE% of 92.91 ± 0.98%, PS of 388.75 ± 18.99 nm, PDI of 0.363 ± 0.01, and ZP of 30.36 ± 0.69 mV. Also, it remained stable for 90 days and manifested great mucoadhesive aspects. The optimum CER was incorporated into calcium alginate to prepare nanocomposite hydrogel. The ex-vivo evaluation illustrated that PNL was permeated in a more prolonged pattern from PNL-loaded CERs nanocomposite related to PNL-composite, optimum CER, and PNL solution. Confocal laser scanning microscopy revealed a perfect accumulation of fluorescein-labeled CERs in the skin. The in-silico investigation illustrated that the PNL was stable when mixed with other ingredients in the CERs and confirmed that PNL is a promising candidate for curing MRSA. Moreover, the PNL-loaded CERs nanocomposite revealed superiority over the PNL solution in inhibiting biofilm formation and eradication. The PNL-loaded CERs nanocomposite showed superiority over the PNL-composite for treating MRSA infection in the in-vivo mice model. Histopathological studies revealed the safety of the tested formulations. In conclusion, PNL-loaded CERs nanocomposite provided a promising, safe cure for MRSA bacterial skin infection.
制备了含有盐酸普萘洛尔（PNL）脂质体（CERs）的纳米复合海藻酸盐水凝胶，作为治疗皮肤耐甲氧西林金黄色葡萄球菌（MRSA）感染的一种重新利用的药物。通过乙醇注射技术，使用不同的神经酰胺、作为表面活性剂的聚氧乙烯氢化蓖麻油以及作为正电荷诱导剂的十二烷基二甲基溴化铵（DDAB）形成CERs。利用Design-Expert软件采用1. 2混合因子设计对CERs进行优化，评估的响应指标为包封率（EE%）、粒径（PS）和zeta电位（ZP）。由5 mg DDAB、神经酰胺VI和聚氧乙烯氢化蓖麻油RH40组成的最佳CER呈现出管状囊泡，包封率为92.91±0.98%，粒径为388.75±18.99 nm，多分散指数为0.363±0.01，zeta电位为30.36±0.69 mV。此外，它在90天内保持稳定，并表现出良好的黏膜粘附性。将最佳CER掺入海藻酸钙中制备纳米复合水凝胶。体外评估表明，与PNL复合物、最佳CER和PNL溶液相比，载有PNL的CERs纳米复合物中PNL的渗透模式更为持久。共聚焦激光扫描显微镜显示荧光素标记的CERs在皮肤中完美积累。计算机模拟研究表明，PNL与CERs中的其他成分混合时是稳定的，并证实PNL是治疗MRSA的有前景的候选药物。此外，载有PNL的CERs纳米复合物在抑制生物膜形成和根除方面优于PNL溶液。在体内小鼠模型中，载有PNL的CERs纳米复合物在治疗MRSA感染方面优于PNL复合物。组织病理学研究揭示了受试制剂的安全性。总之，载有PNL的CERs纳米复合物为MRSA细菌性皮肤感染提供了一种有前景的、安全的治疗方法。
