Chitosan-modulated hyaluronic acid emulsion-based dissolving microneedles for improved stability and controlled release of hydrophilic and lipophilic bioactives

This study investigated the effect of hyaluronic acid–chitosan (HA–CS) polyelectrolyte complex (PEC) modulation on oil-in-water (O/W) emulsion-based dissolving microneedles (DMNs) co-loaded with ascorbic acid (AA) and lycopene (LY). Increasing CS concentration promoted HA–CS complexation, as supported by turbidity and FTIR analyses, and shifted the zeta potential from −30.87 to −16.13 mV. In the resulting DMNs, increasing CS concentration improved needle-tip height accuracy from 72% to 99% and increased maximum compression force from 17.6 to 44.7 N, resulting in improved insertion performance. CS incorporation also improved color stability and retention of DPPH radical-scavenging activity during 14-day storage, with retention ranging from 51 to 88%. Matrix dissolution time increased from 196.67 to 928.33 s with increasing CS concentration. AA release at 4 h decreased from 89% at CS 0% to 54% at 0.5% CS and was largely completed within 24 h, with the Peppas–Sahlin model providing the best fit. In contrast, LY transfer to the receptor phase at 24 h decreased from 67% at 0% CS to 46% at 0.5% CS, with greater membrane-associated retention at 0.5% CS. Multivariate analysis confirmed associations among emulsion properties, DMN matrix resistance, dissolution behavior, and in vitro release characteristics in relation to CS-dependent PEC modulation. These results indicate that CS concentration serves as a tunable parameter for controlling the structural and release properties of PEC-modulated O/W emulsion-based DMNs for hydrophilic and lipophilic bioactive delivery.