Abstract

Dissolving microneedles (MNs) have received a significant amount of interest due to their ability to encapsulate and release drug formulations upon dissolution. This study investigated how the molecular weight of chitosan, a key component of dissolving MNs due to its high biodegradability and biocompatibility, influences the fabrication and transdermal performance of chitosan-based MNs. Chitosan MNs were fabricated using the double-casting method with chitosan solutions of different concentrations (0.5%, 1.5%, and 3% w/v) and molecular weights (low, medium, and high). PVA/PVP solution was used as the supporting base. Several key characteristics of the fabri- cated chitosan MNs were assessed, revealing that the morphology, mechanical strength, and skin insertion characteristics of chitosan MNs were greatly influenced by their molecular weight and concentration. All MNs exhibited well-formed microneedle structures, but only the 3% (w/v) chi- tosan formulations possessed the mechanical strength required for skin penetration. Among them, low molecular weight chitosan at 3% w/v concentration (3LW) exhibited the highest mechanical strength (95.97 mN) and greatest insertion depth (0.52 mm), with over 40% penetration into the fourth parafilm layer. Rhodamine B-loaded 3LW MNs exhibited an initial burst release (61% in 10 minutes) followed by sustained release (81% over 24 hours). Cytotoxicity testing confirmed the low toxicity of chitosan MNs against L929 fibroblasts. These findings suggest that 3LW chitosan MNs represent a promising platform for safe and effective transdermal drug delivery.