الفهرس 
AbstractOnly 14 pages are availabe for public view
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Abstract
The topical route of administration is the most effective route for fast managing of the skin diseases and targeting the therapeutic dosage forms to the site of action with reducing the undesirable systemic side effects with good permeation through the skin layers.
The powerful pharmacological actions of Metformin as anticancer, anti-inflammatory and wound healing activity that evident by this study in-vitro and in-vivo. The anticancer metformin mechanisms based on AMPK (Adenosine mono phosphate activated protein kinase) dependent and independent mechanisms. Metformin promote the angiogenesis that its wound closure action associated with stimulation of nitric oxide.
The present study aimed to formulate MET-HCL in suitable lipid vesicle formulations to provide the maximum benefits from the drug to treat the different skin diseases. The formulations of MET-HCL-loaded liposomes were designed adopting Box–Behnken factorial design. The cast method was employed for preparation of the formulations. Investigation of the effects of different formulation variables on the characteristics of the prepared MET-HCL loaded liposomes resulted in seventeen formulations.
Selection of the best vesicle formulation based on the response surface methodology analysis, displayed 33.6±3.02 % entrapment efficiency, 48.7±2.6 % permeation and 177.8±73.3 nm vesicular size. The selected optimized formulation was also prepared using spraying technique to control the large liposomal vesicle size. Pluronic F-127 was employed for modification of the optimized liposome. The prepared formulations were characterized for entrapment efficiency, permeation percentage, vesicle size and zeta potential. Finally, ethanol was adopted to enhance the formulation parameters through production of MET-HCL loaded ethosomes.
The prepared ethosomes displayed 55.3±0.07 % drug entrapment, 85.8±3.7 % permeation and 5770±179 nm vesicular size.
The anti-proliferative activity of MET-HCL-loaded liposomes and ethosomes was studied employing MTT assay. The in-vitro assay revealed that the novel liposomes and ethosomes formulations had a great potential to enhance the tumor uptake and accumulation of MET-HCL.
The wound healing activity of MET-HCL-loaded ethosomes and liposomes was also studied. The results proved greater efficacy of the studied formulations regarding wound closure of wounded mice in 8 days compared to Mebo® ointment and MET-HCL gel. Complete re-epithelization, neovascularization, reorganization of the dermis with significantly increased collagen deposition with prominent fibroblasts and new hair follicle formation were elucidated by histopathological study. The immuno-histochemical investigation showed an increase in the expression of Insulin-like growth factor-1(IGF-1), Fibroblast growth factor-1 (FGF-1), Platelet-derived growth factor (PDGF-B) and Transforming growth factor beta-1 (TGF-1), while MET-HCL-loaded ethosomes treated group exerted higher induction of the mRNA levels of such growth factors on the basis of bio molecular biology.
In conclusion, the novel lipid vesicles loaded with MET-HCL showed high anti-proliferative activity and wound healing properties. The clinical results were supportive and recommended loading the MET-HCL in liposomal and ethosomal vesicle.