Carvalheiro Manuela, Vieira Jennifer, Faria-Silva Catarina, Marto Joana, Simões Sandra
Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Avenida Professor Gama Pinto, 1649-003, Lisboa, Portugal.
Faculty of Pharmacy, Universidade de Lisboa, Avenida Professor Gama Pinto, 1649-003, Lisboa, Portugal.
Drug Deliv Transl Res. 2021 Apr;11(2):717-728. doi: 10.1007/s13346-021-00910-z. Epub 2021 Feb 3.
Cutaneous leishmaniasis (CL), the most common clinical form of human leishmaniasis, is a non-fatal chronic and disabling disease characterized by erythema and nodular or ulcerative skin lesions that may cause permanent scars and disfigurement. Topical drug delivery represents a simple and efficacious approach to treat CL skin lesions. The association of drugs with nanocarrier systems enhances their permeation properties and increases the drug amount available in the dermis. Here, a deformable lipid vesicle (DLV) was optimized for the topical administration of Amphotericin B (AmB), with the aim of studying and understanding the advantages of this type of delivery system in the transport of a drug through the skin layers. AmB-DVL were characterized in terms of incorporation parameters, stability, and elasticity, and evaluated in vitro for their permeation properties, cytotoxicity, and anti-leishmanial activity. The AmB-DVL exhibited a translucent fluid gel-like aspect and a yellow color, a mean size of 132 nm (PdI ≤ 0.1), zeta potential values around zero (mV), and an AmB incorporation efficiency of 95%. Permeation and penetration assays suggest that AmB-DLV are suitable for topical administration since AmB was detected in the epidermal and dermal skin layers. AmB-DVL was able to reduce promastigote viability in a dose-dependent manner, as well as the number of intracellular amastigotes in THP-1 macrophages. Selectivity index (SI) value for AmB-DLV was considerably higher than that observed for free AmB. Results suggest that DLV may represent an attractive vehicle for dermal delivery of AmB and a new low-cost and safe therapeutic option in CL treatment.
皮肤利什曼病（CL）是人类利什曼病最常见的临床形式，是一种非致命的慢性致残性疾病，其特征为红斑以及结节性或溃疡性皮肤病变，可能会导致永久性疤痕和毁容。局部给药是治疗CL皮肤病变的一种简单有效的方法。药物与纳米载体系统的结合可增强其渗透特性，并增加真皮中可用的药量。在此，对两性霉素B（AmB）的局部给药优化了一种可变形脂质囊泡（DLV），目的是研究和了解这种类型的给药系统在药物透过皮肤各层运输中的优势。对AmB-DVL进行了包封参数、稳定性和弹性方面的表征，并对其渗透特性、细胞毒性和抗利什曼活性进行了体外评估。AmB-DVL呈现半透明的流体凝胶状外观和黄色，平均尺寸为132nm（多分散指数≤0.1），zeta电位值接近零（mV），AmB包封效率为95%。渗透和穿透试验表明，AmB-DLV适用于局部给药，因为在表皮和真皮层中检测到了AmB。AmB-DVL能够以剂量依赖性方式降低前鞭毛体的活力，以及THP-1巨噬细胞内无鞭毛体的数量。AmB-DLV 的选择性指数（SI）值明显高于游离AmB。结果表明DLV可能是一种有吸引力的AmB皮肤给药载体，也是CL治疗中一种新 的低成本且安全的治疗选择。
