Enhanced skin neocollagenesis through the transdermal delivery of poly-L-lactic acid microparticles by using a needle-free supersonic atomizer.

ABSTRACT

In this study, a spindle-type nozzle was designed to accelerate poly-L-lactic acid (PLLA) microparticles to supersonic velocities for the transdermal delivery of these microparticles to rats. This approach is needle- and pain-free and enhances skin collagen regeneration. The addition of PLLA microparticles at a concentration of 2 mg/mL did not hinder the growth of 3 T3 fibroblasts and Raw264.7 macrophages. The TNF-α assay revealed no obvious inflammation effect of PLLA microparticles at a concentration of 1 mg/mL. A time-lapse recording revealed that after being cocultured with PLLA microparticles for 24 h, Raw264.7 macrophages gradually approached and surrounded the PLLA microparticles. When 3 T3 fibroblasts were cocultured with Raw264.7 macrophages, which were stimulated using PLLA microparticles, collagen synthesis was increased by approximately 60 % compared with that in samples without PLLA microparticles. In vivo animal experiments indicated that after the transdermal delivery of 10 shots of PLLA microparticles through the supersonic atomizer, no obvious changes or damage to the back skin of Sprague-Dawley rats was observed. More importantly, numerous PLLA microparticles penetrated the rat epidermis into the dermal layer. We found macrophages and fibroblasts present close to the PLLA microparticles. Moreover, only mild or no inflammation reaction was observed. Masson staining revealed that after 6-week implantation, 6 % and 12 % of PLLA microparticles significantly stimulated collagen regeneration in 6-week-old and 32-week-old rats. In addition, picrosirius red staining revealed a significant increase in collagen regeneration, especially for type III collagen, following the 6-week implantation of PLLA microparticles. In summary, this study demonstrated an easy, pain-free, nondestructive approach for introducing PLLA microparticles into the dermal layer by using a supersonic atomizer to stimulate collagen regeneration in vivo.