Abstract

The skin is a human organ with suitable routes for delivering various active pharmaceutical compounds for therapeutic or cosmetic purposes. Some drugs are available in formulations whose specific desirable properties are best delivered via transdermal routes. One such type of formulation is hydrogels, which are increasingly of interest as innovative vehicles suitable for dermal and transdermal drug delivery. They are three-dimensional (3D) polymeric networks of cross-linked hydrophobic and hydrophilic polymers. Their hydrophilic properties have rendered them attractive for transdermal drug delivery (TDD) and formulations for cosmetic applications. Hydrogels based on hyaluronic acid (HA), a naturally occurring polysaccharide in the human body, have been shown to have good potential for modern cosmetic applications due to their high affinity for water, biocompatibility, non-toxicity, and non-immunogenic nature. They are unlike traditional polymeric hydrogels for cosmetic applications which are undesirable in that they use synthetic polymers, involve long or multi-step inefficient synthesis processes, or include hazardous synthesis methods, such as UV radiation. Therefore, the aim of this research was to develop and synthesise two novel cross-linked HA-based hydrogels: a film and a filler. HA-based hydrogel films are suitable for different TDD applications while injectable hydrogel fillers are suitable for intradermal soft tissue augmentation. In this study, HA-based hydrogel films and fillers were synthesised using a simple, solvent-free cross-linking method, eliminating the need for chemical initiators as traditionally used in UV irradiation cross-linking. Pentaerythritol tetra-acrylate (PT) was used as a cross-linking agent for hydrogel synthesis under a wide pH range with different crosslinking methods, including UV irradiation, microwaving, and oven heating. Cross-linking was best achieved under alkaline conditions and when using the thermal process. The cross-linking of HA-based hydrogel fillers was partial, typical of intradermal injectable fillers. Their rheological properties supported their suitability for aesthetic and biomedical applications. The analysis of residual PT in the novel HA-based hydrogels using gas chromatography (GC) and nuclear magnetic resonance (NMR) techniques confirmed the levels were well below the maximum safe concentrations of PT crosslinker in the films and fillers. Loading of the selected active pharmaceutical agents, including salicylic acid, niacinamide B₃, and urea, in the hydrogel films was high, ranging from 96 % to 100 %. Also, approximately 95-100 % of the active agents were released rapidly through cellulose membrane from the hydrogel films within 10 min, demonstrating their potential suitability as immediate-release drug delivery systems. Finally, the stability of hydrogel films in different solvents and under accelerated shelf conditions was monitored via physical appearance, Fourier-transform infrared spectroscopy (FTIR), and in vitro drug release studies over six months. The hydrogel films in aqueous solvents degraded after 90 days but remained stable in dry form, demonstrating that the aqueous form was less stable than the dry form, and proving that the non-aqueous form was suitable for long-term stability and shelf life.

Overall, the natural hydrogels produced and evaluated over the course of this study are potentially economical and sustainable. Thus, they hold great promise for the pharmaceutical and cosmetic industries’ future advancements in developing effective drug delivery systems, medical or cosmetic surgery procedures, and new-generation skin care products.