Transdermal delivery of mixnoxidil with block copolymer nanoparticles Jongwon Shim * , Hyung Seok Kang, Won-Seok Park, Sang-Hun Han, Junoh Kim, Ih-Seop Chang Nanotechnology Research Laboratory, Skin Research Institute, R&D Center, AMOREPACIFIC Corp., 314-1 Bora-ri, Giheug-eup, Yeongin-si, Gyeonggi-do, Seoul 449-729, South Korea Received 2 September 2003; accepted 31 March 2004 Available online Abstract We evaluated the effect of hydrodynamic size of self-assembled nanoparticles on skin penetration of minoxidil in vitro and in vivo. Self-assembled 40- and 130-nm nanoparticles, both containing minoxidil, were prepared by solvent evaporation of poly(q-caprolactone)-block-poly(ethyleneglycol) and were applied onto the skin of both hairy and hairless guinea pigs in the Franz diffusion cell. In hairy guinea pig skin, the permeation of the minoxidil that incorporated in 40-nm nanoparticles was 1.5- fold higher in the epidermal layer and 1.7-fold higher in the receptor solution than that of 130-nm nanoparticles. Nanoparticle size dependence on the permeation behavior of minoxidil was not observed for hairless guinea pig skin in either the epidermal layer or the receptor solution. Phospholipid liposomes and ethanol – water admixture, on the other hand, containing the same amount of minoxidil did not show differences in the amount of permeation irrespective of the existence of hair follicles. Confocal microscopy coupled with in vivo and in vitro skin permeation results demonstrated that nanoparticles containing solutes penetrated mainly via shunt routes like hair follicles, resulting in skin absorption of solutes. D 2004 Elsevier B.V. All rights reserved. Keywords: Nanoparticles; Skin permeation; Poly(q-caprolactone); Poly(ethyleneglycol); Minoxidil 1. Introduction The stratum corneum is of direct relevance to percutaneous absorption of therapeutic agents due to its principal function as a barrier. The stratum cor- neum is composed of insoluble bundled keratins surrounded by a cell envelope stabilized by cross- linked proteins and covalently bound lipids. The lipids are primarily ceramides, cholesterol, cholesteryl deriv- atives, and fatty acids, which form bilayers surround- ing the corneocytes. Since the other parts of the skin, the epidermis and dermis, do not have barrier properties, the permeation enhancement through the stratum corneum is essential for percutaneous absorption of therapeutic agents. The solute pathways through the stratum corneum can be classified as intercellular routes that exist between the corneocytes, intracellular routes that 0168-3659/$ - see front matter D 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.jconrel.2004.03.028 * Corresponding author. Tel.: +82-31-280-5835; fax: +82-31- 285-2102. E-mail address: jwshim@mac.com (J. Shim). www.elsevier.com/locate/jconrel Journal of Controlled Release 97 (2004) 477 – 484