含两性霉素B的丁香精油基纳米乳剂作为对抗真菌感染的治疗方法

Clove Oil-Based Nanoemulsion Containing Amphotericin B as a Therapeutic Approach to Combat Fungal Infections.

作者信息

de Almeida Marcel Lucas, Matos Ana Paula Dos Santos, Cardoso Veronica da Silva, do Nascimento Tatielle, Santos-Oliveira Ralph, Rocha Leandro Machado, Machado Francisco Paiva, Kenechukwu Franklin Chimaobi, Vermelho Alane Beatriz, Ricci-Júnior Eduardo

机构信息

Laboratório de Desenvolvimento Galênico, Farmácia Universitária, Universidade Federal do Rio de Janeiro, UFRJ, Rio de Janeiro 21941-901, Brazil.

Institute of Drug Technology-Farmanguinhos, Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro 21040-900, Brazil.

出版信息

Pharmaceutics. 2025 Jul 17;17(7):925. doi: 10.3390/pharmaceutics17070925.

DOI:10.3390/pharmaceutics17070925

PMID:40733133

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12300589/

Abstract

Candidiasis, primarily caused by , and sporotrichosis, mainly caused by , are skin fungal infections that pose serious threats to global health. The is a great concern in immunocompromised individuals, and while cause sporotrichosis, an infection commonly found in cats, this disease can be transmitted to humans through scratches or bites. Existing treatments for these fungal infections often cause problems related to resistance and significant side effects. Consequently, development of alternative therapeutic approaches such as nanotechnology-based topical lipid-based formulations is interesting. Thus, the objectives of this study were to prepare clove oil (CO)-in-water nanoemulsions (NEs) containing amphotericin B (AmB) and characterize them with respect to stability, release profile, and in vitro cytotoxic activity against and strains. As a future alternative for the treatment of fungal skin diseases. Chemical analysis of clove oil was obtained by GC-MS. The NEs were produced using an ultrasound (sonicator) method with varying proportions of CO, Pluronic F-127, and AmB. The NEs were characterized by droplet size, morphology, stability and in vitro release profile. The antifungal and cytotoxic activity against , , , and were ascertained employing agar diffusion and colorimetric MTT assay methods. A checkerboard assay was carried out using clove oil and amphotericin B against . Eugenol was the major compound identified in CO at a concentration of 80.09%. AmB-loaded NEs exhibited particle sizes smaller than 50 nm and a polydispersity index below 0.25. The optimal Ne (NEMLB-05) remained stable after 150 days of storage at 4 °C. It exhibited rapid release within the first 24 h, followed by a slow and controlled release up to 96 h. NEMLB-05 more effectively inhibited compared to free AmB and also demonstrated greater activity against , , and . Clove oil and amphotericin B presented synergism inhibiting the growth of . The selected CO-in-water NEs containing AmB demonstrated promising potential as a topical therapeutic alternative for treating fungal infections.

摘要

念珠菌病主要由[未提及具体病因]引起，孢子丝菌病主要由[未提及具体病因]引起，它们都是对全球健康构成严重威胁的皮肤真菌感染。念珠菌病在免疫功能低下的个体中是一个重大问题，虽然[未提及具体病因]会引发孢子丝菌病，这种感染常见于猫，但该疾病可通过抓伤或咬伤传播给人类。现有的这些真菌感染治疗方法常常会引发耐药性相关问题以及严重的副作用。因此，开发基于纳米技术的局部脂质制剂等替代治疗方法很有意义。所以，本研究的目的是制备含有两性霉素B（AmB）的水包丁香精油（CO）纳米乳剂（NEs），并对其稳定性、释放特性以及对[未提及具体菌株]和[未提及具体菌株]菌株的体外细胞毒性活性进行表征。作为治疗真菌性皮肤病的未来替代方法。通过气相色谱 - 质谱联用（GC - MS）对丁香精油进行化学分析。使用超声（超声仪）方法，以不同比例的CO、泊洛沙姆F - 127和AmB制备纳米乳剂。通过液滴大小、形态、稳定性和体外释放特性对纳米乳剂进行表征。采用琼脂扩散法和比色MTT法确定对[未提及具体菌株]、[未提及具体菌株]、[未提及具体菌株]和[未提及具体菌株]菌株的抗真菌和细胞毒性活性。使用丁香精油和两性霉素B对[未提及具体菌株]进行棋盘法测定。丁香精油中鉴定出的主要化合物为丁香酚，浓度为80.09%。负载AmB的纳米乳剂粒径小于50nm，多分散指数低于0.25。最佳纳米乳剂（NEMLB - 05）在4℃储存150天后仍保持稳定。它在最初24小时内表现出快速释放，随后缓慢且可控地释放直至96小时。与游离AmB相比，NEMLB - 05更有效地抑制[未提及具体菌株]，并且对[未提及具体菌株]、[未提及具体菌株]和[未提及具体菌株]也表现出更强的活性。丁香精油和两性霉素B在抑制[未提及具体菌株]生长方面呈现协同作用。所选择的含有AmB的水包CO纳米乳剂作为治疗真菌感染的局部治疗替代方法显示出有前景的潜力。