Novel Hyaluronic Acid ethosomes based gel formulation for topical use with reduced toxicity, better skin permeation, deposition, and improved pharmacodynamics

Hyaluronic Acid (HA) has been applied as an anti-ageing molecule in the form of topical products. Current topical commercial formulations of HA face the limitations of very small and stagnant skin permeation, thereby demanding enduring administration of the formulation to sustain its action. In this study, Lipid-based nanocarriers in the form of ethosomes were formulated in a 1% w/w HA strength and were extensively evaluated in vitro, ex-vivo, and in vivo parameters along with a comparison to it's commercial counterpart. The optimised ethosomes-based HA gel formulation revealed required pH (6.9 ± 0.2), small globule size (1024 ± 9 nm), zeta potential of -6.39 ± 0.2 mV, and 98 ± 1.1% HA content. The ex vivo skin permeation and deposition potenwere conferred on synthetic membrane Strat-M, Human cadaver skin, mice skin, rat skin, and pig skin, and both parameters were found to be much higher in comparison to the commercial topical formulation. Skin deposition capacity of the optimised HA formulation was further confirmed by Scan Electron Microscopy (SEM) and Confocal Laser Scanning Microscopy (CLSM) and it was observed that the developed ethosomal gel formulation got deposited more on the treated skin. The in vivo anti-ageing effect of optimised ethosomal gel on rats was found to be greater when compared to commercial formulation of HA and the developed carrier-based system proved to deliver the HA molecule in very small amounts into the systemic circulation. The results endorse the ethosomal carrier-based formulation of HA as a attractive technique for better local bioavailability of HA.