Studies on Novel Methods for Formulating Novel Cross-Linked Hydrogel Films of Hyaluronic Acid

Abstract

Hyaluronic acid (HA) is a natural polysaccharide with promising applications in modern cosmetic and nutricosmetic products due to its high-water affinity, which is essential for skin hydration, as well as its biocompatibility, biodegradability, non-toxicity, and non-immunogenic nature. In this study, we investigated and optimized the method of crosslinking for formulating novel HA hydrogel films. We used Pentaerythritol Tetra-acrylate (PT) as the cross-linking agent over a range of pH values and used different cross-linking methods (Ultraviolet (UV) radiation, microwaving, and oven heating). The efficacy of the cross-linking reaction was evaluated using swelling studies and Fourier transform infrared (FTIR) spectroscopy for the characterization of the xerogel HA-PT film formulations. We found that HA-PT cross-linked hydrogels are produced under alkaline conditions (pH 11) but not under neutral or acidic conditions. Cross-linked HA-PT xerogel films using UV-irradiation showed excessive swelling indicative of inadequate cross-linking. The oven and microwaving methods produced HA-PT films with high cross-linking density. FTIR data suggest formation of ester bond between the carbonyl of the HA and hydroxyl group of the PT acrylate group. Overall, the oven method was considered better and easier than UV-radiation/microwave methods because it is safer, user-friendly and eco-friendly, and can process larger batches.

Novel Crosslinked HA Hydrogel Films for the Immediate Release of Active Ingredients

“…The preparation of hydrogel was carried out according to [12] with some changes to PT concentration. HA-based hydrogels were formulated with 5% w/w concentration of HA and 25% PT (to be noticed that the 25% PT was from the HA concentration.…”

“…where Mo was the initial weight and Ms was the weight of the swollen hydrogel film at equilibrium. The maximum swelling equilibrium (EWC) was calculated using Equation (2) [12].…”

“…Type I hydrogels are crosslinked three-dimensional polymers holding hydrophilic groups in their structure able to retain water within their structure without dissolving [12]. Hydrogels may be made up of one or more polymers.…”

“…PT (Penta erythritol tetra acrylate) is a tetra-functional acrylate monomer widely used as crosslinker in polymerization. In previous studies, PT has been used as crosslinker for polyethylene oxide (PEO) via UV radiation [17] and for HA via exposure to high temperature (80 • C) in the oven [12]. Such crosslinked hydrogel films can be suitable for the delivery of drugs and cosmetic active ingredients by transdermal and topical (cosmetic) formulations, respectively, via application of the hydrogel film on the intact skin surface.…”

“…The novelty of the HA hydrogel films was reported in our previous paper where we presented a new method of preparation of HA crosslinked hydrogel films, using PT (pentaerythritol tetra acrylate) as the crosslinking agent under high temperature conditions (oven-assisted thermal crosslinking) in high pH [12]. The aim of this follow-up work was to investigate the efficiency of the crosslinked HA hydrogel film as a novel delivery system for pharmaceutical or cosmetic active ingredients; we achieved this aim via the following objectives: (i) feasibility of uploading basic and acidic active ingredients into the novel crosslinked HA hydrogel film via two different loading methods, (ii) characterisation of the properties of the loaded hydrogel films and, provided loading was successful, (iii) release behaviour of the active ingredient from the film.…”