Design of biodegradable bi-compartmental microneedles for the stabilization and the controlled release of the labile molecule collagenase for skin healthcare

Proteins are widely explored as therapeutic agents, but some issues remain alive in their delivery versus target tissues and organs. Especially in the case of water-labile proteins, they undergo rapid failure if not properly stored or once they have encountered the biological environment. In this framework, delivery systems can be very useful to protect such proteins both during storage and during their administration. In particular, polymer microneedles (MNs) represent an interesting tool for the in vivo administration of proteins, avoiding the aggressive gastrointestinal or blood environment. Here, polymer microneedles for the encapsulation and delivery of the labile protein collagenase are presented. Polyvinylpyrrolidone-hyaluronic acid (PVP-HA) microneedles with embedded poly(lactic-co-glycolic acid) (PLGA) microparticles (MPs) were designed in order to achieve a sustained but relatively fast release of the enzyme to avoid its long exposure to water upon administration. PLGA-MPs with tunable porosity were produced by means of a modified double emulsion protocol and their morphological and kinetic properties were characterized by different analytic techniques. Diffusion studies and in vivo experiments were used to assess the release and indentation ability of the proposed MP-based microneedles. The obtained results recommend our bi-compartmental system as a promising biomedical technique paving the way for its efficient use in treating human diseases with labile therapeutic agents. This journal is