Transdermal delivery of estradiol-loaded PLGA nanoparticles using iontophoresis for treatment of osteoporosis.

Estradiol is one of the therapeutic agents for osteoporosis. We have reported transdermal permeability of estradiol-loaded nanoparticles, and permeability effect of estradiol was enhanced by using nanoparticle system and iontophoresis [Colloids and Surfaces B: Biointerfaces97 (2012), 84-89]. This study was conducted in vivo to evaluate therapeutic efficacy of the estradiol-loaded PLGA nanoparticles for osteoporosis. Prior to the in vivo study, we have determined the surface charge density of the particles and found they have negatively charged polyelectrolyte layers on the surfaces. Ovariectomized female Sprague-Dawley rats were used as an animal model of osteoporosis. They were separated into three groups by administration route of estradiol-loaded PLGA nanoparticles, passive diffusion group, iontophoresis group and control. After treatment, we have measured bone mineral density of spine using an X-ray computed tomography system. Bone mineral density after iontophoresis was significantly higher than that of passive diffusion and control group. By usage of iontophoresis, the nanoparticles were permeated through follicles and migrated into capillary vessel around follicles, and the loaded drug reached effective blood concentration in plasma of rat. From this study, we found that the combination with charged nanoparticle system and iontophoresis is useful to osteoporosis treatment.