Anti-ageing Potential of Metformin Loaded Fennel Oil-Based Nanoemulgel: A Promising Novel Approach for Ultraviolet...

Ageing produces structural alteration of skin tissue when exposed to UV radiation, pollution and smoking, resulting in functional decline and mortality of the cells. The proposed study aimed at developing a commercially scalable fennel oil (FO) based metformin-loaded nanoemulsion (MTF-NE) incorporated in the hydrogel (MTF-HYD-NEG) providing anti-ageing effect.

The scalable development of phytocompound incorporated nanoemulsion was done using a multi-step process involving excipient screening, optimization of nanoemulsion and thermodynamic stability assessment. The MTF-NE was developed using aqueous titration method containing Tween 80 as the surfactant and Transcutol P as the co-surfactant. The optimized nanoemulsion was incorporated into a hydrogel to form MTF-HYD-NEG. The formulation was characterized based on globule size, polydispersity index (PDI), zeta potential, spreadability, viscosity, and permeability. In vitro drug release and ex vivo permeation studies were conducted to assess sustained drug release. Confocal laser scanning microscopy (CLSM) was used to evaluate skin penetration. The in vivo studies were conducted using UV-B radiation induced mice models and old mice models to assess the anti-ageing efficacy through histopathological analysis, immunohistochemistry (MMP-1 expression), and biochemical assays (GSH, SOD, CAT, and MDA levels).

The characterization of the optimized MTF-NE exhibited a monodispersed pattern with an average globule size of 261.1 nm, PDI of 0.1305 and zeta potential of -4.4 mV. The MTF-NE was then converted into a hydrogel. The permeability of the MTF-HYD-NEG was assessed by in vitro release and ex vivo permeation studies that demonstrated a sustained release effect of Metformin (MTF) with the value of 71.565 ± 4.995 % over 24 hours and 4.503 ± 2.669 mg/cm² over 8 hours of study. Additionally, the release profile was further validated by the confocal microscopy through the mice's skin tissue. The mean intensity was observed to be 53.472 which was retained at 4.472 at 50 µm depth of permeation demonstrating the better penetration of the nanocarrier. The data displayed by histopathology and MMP-1 expression by immunohistochemistry showed recuperation in the dermal tissue of the mice model seen in the post-treatment group of MTF-HYD-NEG in comparison to the control group and conventional treatment groups and depletion in MMP-1 production, improved dermal collagen and diminished wrinkles.

The results of the MTF-HYD-NEG formulation displayed enhanced permeability with a prolonged effect, depicting a reduction in MMP-1 expression, which could serve as a promising anti-ageing and antioxidant preparation attributed to the presence of a fennel oil base.