High-loading hyaluronic acid dissolving microneedles for child-friendly dermal and transdermal delivery of...

The clinical utility of doxycycline (DX) in pediatrics is constrained by delivery-related side effects, including dysgeusia, gastrointestinal distress, and phlebitis, which often compromise adherence. Dissolving microneedles (DMNs) represent a minimally invasive strategy to circumvent these limitations; however, pediatric-oriented platforms remain underexplored. In this study, a hyaluronic acid (HA)-based DMNs array was developed for dermal DX delivery and systematicallyoptimized. The formulation was characterized by SEM, DSC, and FTIR, assessing mechanical strength, dissolution, and skin insertion. Antimicrobial efficacy was examined via well diffusion assay, followed by ex vivo permeation studies using Franz diffusion cells. Biocompatibility and therapeutic efficacy were evaluated in vivo in a murine skin model, and stability was established in accordance with the ICH guidelines. The optimized DX-loaded MNS (DX-MNs) achieved a high drug loading efficiency (∼99 %), sufficient mechanical robustness to penetrate the skin, and rapid dissolution within 90 s, enabling a biphasic ex vivo DX permeation profile over 36 h, reaching ∼97.5 % cumulative permeation. DX-MNs preservedthe antimicrobial activity of DX in vitro. In vivostudies demonstrated marked wound contraction (∼99 %) by day 7 following both local and distant-site patch applications, consistent with systemic exposure. The patches were well-tolerated and remained stable (>95 % recovery) for six months under tested storage conditions. Collectively, these findings illustrate that the developed platform could overcomekey delivery barriers associated with conventional DX, supporting DMNs as a safe, child-friendly platform for localized and potential systemic antibiotic delivery. This study underscores the translational prospects of DMNs to improve treatment outcomes for pediatric infectious diseases.