title: Enhanced transdermal permeability of estradiol using combination of PLGA nanoparticles system and iontophoresis.
abstract: Estradiol is a therapeutic agent for treatment of perimenopausal symptoms and osteoporosis. Conventional oral or intravenous administration of estradiol has many problems, such as, metabolization in gastrointestinal tract and liver, pain by using an injection needle, rapid increase of drug levels in blood and fast clearance with unwanted side effects including thrombosis, endometriosis and uterus carcinoma. The use of nanocarriers for transdermal delivery has been studied because of their ability to deliver therapeutic agents for long time with a controlled ratio, escaping from the first pass effect by liver. In this study, permeability of estradiol-loaded PLGA nanoparticles through rat skin was studied. Higher amount of estradiol was delivered through skin when estradiol was loaded in nanoparticles than estradiol was free molecules. Also, iontophoresis was applied to enhance the permeability of nanoparticles. When iontophoresis was applied, permeability of estradiol-loaded PLGA nanoparticles was much higher than that obtained by simple diffusion of them through skin, since they have negative surface charges. They were found to penetrate through follicles mainly. Also, enhanced permeability effect of estradiol by using nanoparticle system and iontophoresis were observed in vivo. The combination of charged nanoparticle system with iontophoresis is useful for effective transdermal delivery of therapeutic agents.
authors.affiliation: Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Chiba, Japan.
authors.forename: Keishiro
authors.initials: K
authors.lastname: Tomoda
authors.forename: Aya
authors.initials: A
authors.lastname: Watanabe
authors.forename: Kenichi
authors.initials: K
authors.lastname: Suzuki
authors.forename: Toshio
authors.initials: T
authors.lastname: Inagi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Terada
authors.forename: Kimiko
authors.initials: K
authors.lastname: Makino
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D004958:Estradiol / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D007478:Iontophoresis / Q000379:methods*; D019344:Lactic Acid / Q000737:chemistry*; D008297:Male; D053758:Nanoparticles / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017207:Rats, Sprague-Dawley; D012869:Skin Absorption / Q000502:physiology
chemical_list: D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D004958:Estradiol