Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 20, Issue 15, Pages -Publisher
MDPI
DOI: 10.3390/ijms20153644
Keywords
indomethacin; l-menthol; nanoparticle; skin; drug delivery
Funding
- Japan Society for the Promotion of Science [18K06769]
- Grants-in-Aid for Scientific Research [18K06769] Funding Source: KAKEN
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This study designed the transdermal formulations containing indomethacin (IMC)-1% IMC was crushed with 0.5% methylcellulose and 5% 2-hydroxypropyl-beta-cyclodextrin by the bead mill method, and the milled IMC was gelled with or without 2% l-menthol (a permeation enhancer) by Carbopol((R)) 934 (without menthol, N-IMC gel; with menthol, N-IMC/MT gel). In addition, the drug release, skin penetration and percutaneous absorption of the N-IMC/MT gel were investigated. The particle sizes of N-IMC gel were approximately 50-200 nm, and the combination with l-menthol did not affect the particle characterization of the transdermal formulations. In an in vitro experiment using a Franz diffusion cell, the skin penetration in N-IMC/MT gel was enhanced than the N-IMC gel, and the percutaneous absorption (AUC) from the N-IMC/MT gel was 2-fold higher than the N-IMC gel. On the other hand, the skin penetration from the N-IMC/MT gel was remarkably attenuated at a 4 degrees C condition, a temperature that inhibits all energy-dependent endocytosis. In conclusion, this study designed transdermal formulations containing IMC solid nanoparticles and l-menthol, and found that the combination with l-menthol enhanced the skin penetration of the IMC solid nanoparticles. In addition, the energy-dependency of the skin penetration of IMC solid nanoparticles was demonstrated. These findings suggest the utility of a transdermal drug delivery system to provide the easy application of solid nanoparticles (SNPs).
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