Rapidly dissolving microneedles for the delivery of cubosome-like liquid crystalline nanoparticles with sustained release of rapamycin

Abstract

In this study, we developed a system for the transdermal delivery and controlled release of the hydrophobic immunosuppressive drug rapamycin, foreseeing an application in psoriasis treatment. To do so, rapamycin was encapsulated in phytantriol-based cubosome-like liquid crystalline nanoparticles stabilized with pluronic F127. The final mass percent composition of the lipid nanoparticles was 0.25% phytantriol, 0.1% pluronic F127, 4.75% ethanol and 94.9% water. These particles showed a rapamycin encapsulation efficiency above 95% and a sustained in vitrodrug release profile throughout 14 days. Subsequently the rapamycin-carrying particles were incorporated into rapidly dissolving microneedle patches composed of a polymeric matrix of poly(vinylpyrrolidone) and poly(vinyl alcohol). Confocal microscopy allowed to infer the preferential distribution of the cubosome-like particles at the tip and baseplate of the microneedles. The fabricated microneedles showed successful piercing and deposition of the loaded cubosome-like particles on a skin-mimicking agarose gel. Finally, the rapamycin-loaded cubosome-like particles showed antiproliferative activity in natural killer cells in vitro. The results here presented show the potential of the developed system to deliver cubosome-like particles into the skin and promote the sustained release of rapamycin in the context of immunomodulation.

Keywords: Cubosomes; Microneedles; Rapamycin; Sustained drug release; Transdermal.