title: Estradiol-loaded PLGA nanoparticles for improving low bone mineral density of cancellous bone caused by osteoporosis: Application of enhanced charged nanoparticles with iontophoresis.
abstract: Postmenopausal osteoporosis among older women, which occurs by an ovarian hormone deficiency, is one of the major public health problems. 17 β-estradiol (E2) is used to prevent and treat this disease as a drug of hormone replacement therapy. In oral administration, E2 is significantly affected by first-pass hepatic metabolism, and high dose administration must be needed to obtain drug efficacy. Therefore, alternative administration route is needed, and we have focused on the transdermal drug delivery system. In this study, we have prepared E2-loaded poly(DL-lactide-co-glycolide) (PLGA) nanoparticles for osteoporosis by using a combination of an antisolvent diffusion method with preferential solvation. The average particle diameter of the nanoparticles was 110.0±41.0nm and the surface charge number density was 82 times higher than that of conventional E2-loaded PLGA nanoparticles. Therapeutic evaluation of E2-loaded PLGA nanoparticles was carried out using ovariectomized female rats. Therapeutic efficacy was evaluated to measure bone mineral density of cancellous bone using an X-ray CT system. When the E2-loaded PLGA nanoparticles were administrated once a week, bone mineral density was significantly higher than that of the non-treated group at 60days after the start of treatment. Also, in the group administered this nanoparticle twice a week, the bone mineral density increased significantly at 45days after the start of treatment. From these results, it was revealed that E2-loaded PLGA nanoparticles with iontophoresis were useful to recover bone mineral density of cancellous bone, and it was also suggested that they extend the dosing interval of E2.
authors.affiliation: Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641, Yamazaki, Noda, Chiba 278-8510, Japan; Center for Drug Delivery Research, Tokyo University of Science, 2641, Yamazaki, Noda, Chiba 278-8510, Japan; Center for Physical Pharmaceutics, Tokyo University of Science, 2641, Yamazaki, Noda, Chiba 278-8510, Japan.
authors.forename: Issei
authors.initials: I
authors.lastname: Takeuchi
authors.affiliation: Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641, Yamazaki, Noda, Chiba 278-8510, Japan.
authors.forename: Shiori
authors.initials: S
authors.lastname: Kobayashi
authors.affiliation: Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641, Yamazaki, Noda, Chiba 278-8510, Japan.
authors.forename: Yukari
authors.initials: Y
authors.lastname: Hida
authors.affiliation: Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641, Yamazaki, Noda, Chiba 278-8510, Japan; Center for Drug Delivery Research, Tokyo University of Science, 2641, Yamazaki, Noda, Chiba 278-8510, Japan; Center for Physical Pharmaceutics, Tokyo University of Science, 2641, Yamazaki, Noda, Chiba 278-8510, Japan. Electronic address: makino@rs.noda.tus.ac.jp.
authors.forename: Kimiko
authors.initials: K
authors.lastname: Makino
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000737:chemistry / Q000494:pharmacology*; D000071556:Cancellous Bone / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D004339:Drug Compounding / Q000379:methods; D004958:Estradiol / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D005269:Femur / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D007478:Iontophoresis / Q000379:methods; D019344:Lactic Acid / Q000737:chemistry; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry / Q000648:ultrastructure; D010024:Osteoporosis / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D010052:Ovariectomy / Q000009:adverse effects; D010539:Permeability; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011142:Polyvinyl Alcohol / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D055672:Static Electricity; D046509:Tissue Culture Techniques; D014057:Tomography, X-Ray Computed
chemical_list: D050071:Bone Density Conservation Agents; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D004958:Estradiol; D011142:Polyvinyl Alcohol
keywords: Bone mineral density; Estradiol transdermal administration; Iontophoresis; Nanoparticle; Osteoporosis