Composites of hyaluronic acid and various amino acids as structural materials for dissolvable microneedles

Twenty-one amino acids (AAs) were examined as additives to hyaluronic acid (HA) for the development of dissolving microneedles with sufficient mechanical properties and enhanced loading capacity for curcumin, a model hydrophobic drug. Only arginine (Arg) yielded a sturdy, homogeneous, transparent composite with no precipitation when combined with HA at concentrations of up to 50%. The HA-Arg composite has a superior Young's modulus and dissolves in water more rapidly compared to HA. The incorporation of curcumin into HA-Arg resulted in no curcumin precipitation within the HA-Arg film, while the incorporation of curcumin into HA led to significant curcumin precipitates in the HA matrix. In addition to Arg, amino acids that enhance Young's modulus when combined with HA include threonine (Thr), hydroxyproline (Hyp), alanine (Ala), and tyrosine (Tyr). Microneedles made from the mixtures of HA with each of these five AAs could penetrate ex vivo porcine skin well. Among these five AAs, only the hydrophilic ones-Arg, Thr, and Hyp-when combined with HA, significantly increase the rate of water solubility. The microneedles made from the composites of HA and each of these three AAs showed faster diffusion in porcine skin tissue relative to pure HA microneedles.