Junko Yokota1, Shojiro Kyotani2. 1. Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima, Japan; Department of Pharmacy, Kochi Medical School Hospital, Kochi, Japan. Electronic address: jm-yokotaj@kochi-u.ac.jp. 2. Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima, Japan.
Abstract
BACKGROUND: This study aims to evaluate the influence of nanoparticle size on the in vitro percutaneous penetration and retention and in vivo anti-inflammatory efficacy of percutaneously delivered non-steroidal anti-inflammatory drugs. METHODS: Indomethacin, ketoprofen and piroxicam were incorporated into nanoparticles. The nanoparticles, or the bulk-drug equivalents, were suspended in a hydrophilic ointment and compared for their ability to facilitate percutaneous drug penetration and retention in vitro. The formulations were applied cutaneously in a carrageenan-induced footpad inflammation model (acute inflammation) and an adjuvant-induced arthritis model (chronic inflammation) in rats and were assessed for their anti-inflammatory efficacy and potency. RESULTS: The nanoparticle formulations demonstrated a substantially smaller particle size compared with the bulk-drug formulations. The nanoparticles notably increased drug penetration and retention in vitro. In both the acute and chronic inflammation models, the nanoparticle formulations demonstrated significantly higher anti-inflammatory activity than that of their corresponding bulk-drug formulation at an equivalent dose, and produced better overall healing. CONCLUSION: The nanoparticle formulations are highly effective as percutaneous drug carriers, and demonstrate that decreasing particle size leads to increased efficacy and potency. The exploitation of such nanotechnology could drive the development of more effective percutaneous therapeutics.
BACKGROUND: This study aims to evaluate the influence of nanoparticle size on the in vitro percutaneous penetration and retention and in vivo anti-inflammatory efficacy of percutaneously delivered non-steroidal anti-inflammatory drugs. METHODS:Indomethacin, ketoprofen and piroxicam were incorporated into nanoparticles. The nanoparticles, or the bulk-drug equivalents, were suspended in a hydrophilic ointment and compared for their ability to facilitate percutaneous drug penetration and retention in vitro. The formulations were applied cutaneously in a carrageenan-induced footpad inflammation model (acute inflammation) and an adjuvant-induced arthritis model (chronic inflammation) in rats and were assessed for their anti-inflammatory efficacy and potency. RESULTS: The nanoparticle formulations demonstrated a substantially smaller particle size compared with the bulk-drug formulations. The nanoparticles notably increased drug penetration and retention in vitro. In both the acute and chronic inflammation models, the nanoparticle formulations demonstrated significantly higher anti-inflammatory activity than that of their corresponding bulk-drug formulation at an equivalent dose, and produced better overall healing. CONCLUSION: The nanoparticle formulations are highly effective as percutaneous drug carriers, and demonstrate that decreasing particle size leads to increased efficacy and potency. The exploitation of such nanotechnology could drive the development of more effective percutaneous therapeutics.