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Metformin-loaded ethosomes with promoted anti-proliferative activity in melanoma cell line B16, and wound healing aptitude: Development, characterization and in vivo evaluation

体内 伤口愈合 药理学 渗透 二甲双胍 离体 化学 医学 体外 免疫学 糖尿病 生物 生物化学 内分泌学 生物技术
作者
Shrouk Magdy,Eman Alaaeldin,Zeinab Fathalla,Rania Alaaeldin,Mahmoud A. Elrehany,Entesar Ali Saber,Rasha T.A. Abdel-Aziz,Heba F. Mansour
出处
期刊:International Journal of Pharmaceutics [Elsevier BV]
卷期号:621: 121781-121781 被引量:17
标识
DOI:10.1016/j.ijpharm.2022.121781
摘要

The present work deals with the development of metformin-loaded ethosomes for localized treatment of melanoma and wound healing. Different ethosomal formulations were prepared using different concentrations of ethanol adopting injection technique. The developed formulations were investigated for entrapment efficiency, ex-vivo skin permeation, vesicle size, morphology and permeation kinetics. The optimized formulation was loaded in 5 % carbomer gel that was evaluated for skin permeation, cytotoxic effect against melanoma mice B16 cell line and for wound healing action. Ethosomes having 30 % v/v ethanol displayed superior entrapment for metformin % (55.3 ± 0.07); and a highly efficient permeation via mice skin (85.8 ± 3.7). The related carbomer ethosomal gel exhibited higher skin permeation compared to the untreated metformin gel (P < 0.001). The metformin ethosomes had a substantial antiproliferative activity against melanoma B16 cells compared to corresponding metformin solution as shown by the lower IC50 values (56.45 ± 1.47 and 887.3 ± 23.2, respectively, P < 0.05) and tumour cell viability (P < 0.05). The ethosomal system had a significant wound healing action in mice (80.5 ± 1.9%) that was superior to that of the marketed product Mebo® ointment (56 ± 1 %), P < 0.05. This ethosomal system demonstrated outstanding induction of the mRNA levels of growth factors (IGF-1, FGF-1, PDGF-B and TGF-β) that are essential in the healing process. Those findings were supported by histopathologic examination of wound sections of different treated groups. Thus, the study proved that metformin ethosomes as a promising drug delivery system and a conceivable therapeutic approach for treatment of melanoma and wound healing.
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