Department of Pharmaceutics, Faculty of Pharmacy, Minia University, Minia, Egypt; Department of Pharmaceutics Faculty of Pharmacy, Deraya University, Minia, Egypt.
Department of Pharmaceutics, Faculty of Pharmacy, Minia University, Minia, Egypt; Department of Pharmaceutics Faculty of Pharmacy, Deraya University, Minia, Egypt.
Int J Pharm. 2022 Jun 10;621:121781. doi: 10.1016/j.ijpharm.2022.121781. Epub 2022 Apr 28.
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.
本工作涉及开发载有二甲双胍的醇质体，用于局部治疗黑色素瘤和伤口愈合。采用注射技术，用不同浓度的乙醇制备不同的醇质体配方。对所开发的配方进行包封效率、离体皮肤渗透、囊泡大小、形态和渗透动力学的研究。将优化的配方载入 5%卡波姆凝胶中，评估其对黑色素瘤小鼠 B16 细胞系的皮肤渗透、细胞毒性作用以及对伤口愈合作用。含有 30%v/v 乙醇的醇质体显示出对二甲双胍的优越包封效率（55.3±0.07）；并通过小鼠皮肤实现了高效渗透（85.8±3.7）。与未处理的二甲双胍凝胶相比，载有二甲双胍的醇质体凝胶表现出更高的皮肤渗透（P<0.001）。与相应的二甲双胍溶液相比，二甲双胍醇质体对黑色素瘤 B16 细胞具有显著的抗增殖活性，表现为较低的 IC50 值（分别为 56.45±1.47 和 887.3±23.2，P<0.05）和肿瘤细胞活力（P<0.05）。醇质体系统在小鼠中具有显著的伤口愈合作用（80.5±1.9%），优于市售产品 Mebo®软膏（56±1%），P<0.05。该醇质体系统在诱导生长因子（IGF-1、FGF-1、PDGF-B 和 TGF-β）的 mRNA 水平方面表现出色，这些因子在愈合过程中是必不可少的。这些发现得到了不同处理组伤口切片的组织病理学检查的支持。因此，该研究证明了二甲双胍醇质体作为一种有前途的药物传递系统和一种可行的治疗黑色素瘤和伤口愈合的方法。
