Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, The British University in Egypt, El-Sherouk City, Cairo, Egypt.
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Int J Pharm. 2024 Dec 5;666:124763. doi: 10.1016/j.ijpharm.2024.124763. Epub 2024 Sep 25.
Burn wounds remain a significant global health concern, frequently exacerbated by bacterial infections that hinder healing and raise morbidity rates. Cefdinir, a third-generation cephalosporin antibiotic, is used to treat various conditions, but it has limitations such as low water solubility, limited bioavailability, and a short biological half-life. This study aimed to fabricate and optimize novel surfactant-based Cefdinir-loaded chitosan nanoparticles (CFD-CSNPs) for enhancing topical CFD delivery and efficacy in burn healing. Box-Behnken Design (BBD) was employed to develop optimized CFD-CSNPs using Design Expert® software, where the independent factors were chitosan concentration, chitosan: sodium tripolyphosphate ratio, pH, and surfactant type. Particle size PS, zeta potential ZP, Polydispersity index PDI, and entrapment efficiency EE% were evaluated as dependent factors. CFD-CSNPs were produced using the ionic gelation method. The optimized formula was determined and then examined for further in vitro and in vivo assessments. The optimized CFD-CSNPs exhibited acceptable PS, PDI, and ZP values. The EE% of CFD from CSNPs reached 57.89 % ± 1.66. TEM analysis revealed spherical morphology. In vitro release studies demonstrated a biphasic release profile up to (75.5 % ± 3.8) over 48 hrs. The optimized CFD-CSNPs showed improved antimicrobial efficacy against the tested microorganisms, exhibiting superior performance for both biofilm prevention and eradication. Enhanced wound healing activity was achieved by the optimized CFD-CSNPs in both in vitro and in vivo studies as confirmed by scratch wound assay and skin burn mice model. The current study advocates the efficacy of the innovative topical application of CFD-CSNPs for wound healing purposes and treatment of wound infections.
烧伤创面仍然是一个重大的全球健康问题，常因细菌感染而恶化，从而阻碍愈合并提高发病率。头孢地尼是一种第三代头孢菌素抗生素，用于治疗多种疾病，但存在水溶性低、生物利用度有限和生物半衰期短等局限性。本研究旨在制备和优化新型基于表面活性剂的载头孢地尼壳聚糖纳米粒（CFD-CSNPs），以增强局部 CFD 递药和促进烧伤愈合的疗效。采用 Box-Behnken 设计（BBD），使用 Design Expert®软件对 CFD-CSNPs 进行优化，其中独立因素为壳聚糖浓度、壳聚糖：三聚磷酸钠比、pH 值和表面活性剂类型。粒径 PS、zeta 电位 ZP、多分散指数 PDI 和包封效率 EE%作为依赖因素进行评估。采用离子凝胶化法制备 CFD-CSNPs。确定优化配方，然后进行进一步的体外和体内评估。优化后的 CFD-CSNPs 表现出可接受的 PS、PDI 和 ZP 值。CSNPs 中 CFD 的 EE%达到 57.89%±1.66%。TEM 分析显示出球形形态。体外释放研究表明，在 48 小时内达到（75.5%±3.8）的两相释放曲线。优化后的 CFD-CSNPs 对测试的微生物表现出更好的抗菌功效，在生物膜预防和清除方面均表现出优异的性能。优化后的 CFD-CSNPs 在体外和体内研究中均显示出增强的伤口愈合活性，通过划痕实验和皮肤烧伤小鼠模型得到证实。本研究提倡将创新的 CFD-CSNPs 局部应用于伤口愈合和治疗伤口感染。
