Journal
INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume 591, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.ijpharm.2020.119942
Keywords
Microneedles; Rapamycin; Cubosomes; Transdermal; Sustained drug release
Categories
Funding
- Norte2020 Funding Program, N2020-PE-Nanothechnology-Based Functional Solutions (NBFS) project [NORTE-01-0145-FEDER000019]
- Ramon Areces Foundation [BEVP30A5827]
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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 plumnic F127. The final mass percent composition of the lipid nanoparticles was 0.25% phytantriol, 0.1% plumnic F127, 4.75% ethanol and 94.9% water. These particles showed a rapamycin encapsulation efficiency above 95% and a sustained in vitro drug 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 agamse 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.
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