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载药脂肪酸的纳米工程脂质-聚合物杂化纳米粒:在皮肤药动学特征和耐甲氧西林金黄色葡萄球菌感染烧伤创面模型上的研究

Nano-engineered lipid-polymer hybrid nanoparticles of fusidic acid: an investigative study on dermatokinetics profile and MRSA-infected burn wound model.

机构信息

University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Studies, Panjab University, Chandigarh, 160 014, India.

UGC-Centre of Excellence in Applications of Nanomaterials, Nanoparticles & Nanocomposites (Biomedical Sciences), Panjab University, Chandigarh, 160 014, India.

出版信息

Drug Deliv Transl Res. 2019 Aug;9(4):748-763. doi: 10.1007/s13346-019-00616-3.

Abstract

Staphylococcus aureus (SA) and methicillin-resistant Staphylococcus aureus (MRSA) have been a major cause of morbidity in thermally injured patients. The skin barrier gets disrupted and loss of immunity further makes burn sites an easy target for bacterial colonization. In the current study, combined potential of lipid-polymer hybrid nanoparticles (LPHNs) with fusidic acid was explored as a promising strategy toward combating resistant bacteria in burn wound infection sites. The developed systems exhibited particle size (310.56 ± 5.22 nm), zeta potential (24.3 ± 4.18 mV) and entrapment efficiency (78.56 ± 3.56%) with a spherical shape. The hybrid nanoparticles were further gelled into carbopol and demonstrated better permeation (76.53 ± 1.55%) and retention characteristics (56.41 ± 4.67%) as compared to the conventional formulation. The topical delivery of FA into the skin layers by FA-LPHN gel was found to be significantly higher (p < 0.05) compared to FA-CC. The in vivo potential was further assessed in murine burn wound model inflicted with MRSA 33591 bacterium with the determination of parameters like bacterial burden, wound contraction, morphological and histopathological examination of wounds. The bacterial count decreased drastically in FA-LPHN gel group (5.22 log CFU/mL) on day 3 with significant difference in comparison to FA-CC. The wound size reduction in FA-LPHN gel (68.70 ± 3.65%) was higher as compared to FA-CC (73.30 ± 4.23%) and control groups (83.30 ± 4.40%) on day 5. The current study presents a safe and effective formulation strategy for the treatment of MRSA-infected burn wounds by providing moist environment and prevention from bacterial infection.

摘要

金黄色葡萄球菌(SA)和耐甲氧西林金黄色葡萄球菌(MRSA)一直是热烧伤患者发病率的主要原因。皮肤屏障被破坏,免疫力进一步下降,使烧伤部位容易受到细菌定植。在目前的研究中,探索了脂质-聚合物杂化纳米粒子(LPHN)与夫西地酸的联合潜力,作为一种有前途的策略,以对抗烧伤感染部位的耐药菌。所开发的系统表现出粒径(310.56±5.22nm)、Zeta 电位(24.3±4.18mV)和包封效率(78.56±3.56%),呈球形。杂化纳米粒子进一步凝胶化到卡波姆中,并表现出更好的渗透性(76.53±1.55%)和保留特性(56.41±4.67%),与常规制剂相比。与 FA-CC 相比,FA-LPHN 凝胶将 FA 递送至皮肤层中的作用明显更高(p<0.05)。在 MRSA 33591 细菌感染的小鼠烧伤模型中进一步评估了其体内潜力,并确定了细菌负荷、伤口收缩、伤口形态和组织病理学检查等参数。在第 3 天,FA-LPHN 凝胶组的细菌计数急剧下降(5.22logCFU/mL),与 FA-CC 相比有显著差异。FA-LPHN 凝胶(68.70±3.65%)的伤口缩小率高于 FA-CC(73.30±4.23%)和对照组(83.30±4.40%)在第 5 天。本研究通过提供湿润环境和防止细菌感染,为治疗 MRSA 感染的烧伤创面提供了一种安全有效的制剂策略。

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