Solvent-Controlled Microstructure Engineering of Biodegradable PCLDA Microneedles for Sustainable Protein Delivery

Biodegradable polymeric microneedles have attracted attention as sustainable transdermal drug delivery systems because they enable localized biomolecule delivery while eliminating long-term polymer accumulation. Beyond polymer composition, controlling microstructure offers a strategy for regulating therapeutic release. In this study, biodegradable polycaprolactone diacrylate (PCLDA) microneedles were developed to investigate the influence of solvent-controlled microstructure on protein release.

PCLDA was synthesized by esterification of polycaprolactone diol with acrylic acid and fabricated into microneedle arrays using PDMS molds from a DLP-SLA 3D-printed master. Its biodegradability was confirmed by hydrolytic degradation, exhibiting degradation ratios of 26.8% at 36.5 °C and 83.9% at 70 °C after three months.

To investigate the structure–property relationship without altering the polymer chemistry, different post-fabrication washing solvents were used to tailor the microneedle morphology. SEM analysis showed that ethanol washing preserved a compact microstructure, whereas deionized water (DW) washing induced solvent–nonsolvent phase separation through DMSO–water exchange, generating interconnected porous structures. Fish-derived protein was used to evaluate release behavior. Porous microneedles promoted rapid protein release, whereas dense microneedles exhibited slower, sustained release. These findings demonstrate that solvent-induced microstructural engineering regulates protein release kinetics without changing the polymer composition.

This study highlights solvent-controlled microstructure engineering as a strategy for tuning the structure–property relationship of biodegradable soft materials. The developed PCLDA microneedle platform provides a sustainable approach to transdermal drug delivery by enabling programmable protein release through microstructural design.