title: Design and evaluation of poly(DL-lactic-co-glycolic acid) nanocomposite particles containing salmon calcitonin for inhalation.
abstract: Salmon calcitonin, for the treatment of calcium homeostasis and bone remodeling, was used as a model peptide drug and adsorbed on the surface of biodegradable polymeric poly(dl-lactic-co-glycolic acid) (PLGA) nanospheres. Subsequently, the nanospheres were treated using lyophilizer and loaded onto inhalable carrier using Mechanofusion to obtain nanocomposite particles suitable for inhalation. The physicochemical properties and in vitro inhalation properties of the nanocomposite particles were investigated. The pulmonary distribution and pharmacological effect were also evaluated in male Wistar rats. The results showed that the drug loading efficiency of salmon calcitonin on PLGA nanospheres were exceeding 96% (w/w). Inhalation efficiency of the lyophilized PLGA nanospheres was largely improved after they were loaded on the surface of inhalable carrier. Over 50% (w/w) of the lyophilized PLGA nanospheres could be deposited in the alveoli section after intratracheal administration to male Wistar rats, while a rapid elimination rate of the lyophilized nanospheres from the lung was found in pulmonary distribution study. The in vivo pharmacological study showed that the nanocomposite particles exhibited superior hypocalcemic action over salmon calcitonion solution and the lyophilized nanospheres. It suggested that the Mechanofusion(TM) technique can impart improved inhalation properties to the lyophilized nanospheres for pulmonary delivery of therapeutic peptide drugs.
authors.affiliation: Laboratory of Pharmaceutical Engineering, Gifu Pharmaceutical University, 5-6-1 Mitahora-Higashi, Gifu 502-8585, Japan.
authors.forename: Mingshi
authors.initials: M
authors.lastname: Yang
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Homare
authors.initials: H
authors.lastname: Kurashima
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Takeuchi
authors.forename: Toyokazu
authors.initials: T
authors.lastname: Yokoyama
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tsujimoto
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kawashima
mesh_terms: D000280:Administration, Inhalation; D000327:Adsorption; D000818:Animals; D015415:Biomarkers / Q000097:blood; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D002116:Calcitonin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D002118:Calcium / Q000097:blood; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D004337:Drug Carriers; D004339:Drug Compounding; D005612:Freeze Drying; D019344:Lactic Acid / Q000737:chemistry*; D008168:Lung / Q000378:metabolism; D008297:Male; D053761:Nanocomposites; D054118:Nanospheres; D036103:Nanotechnology; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011208:Powders; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods; D014018:Tissue Distribution
chemical_list: D015415:Biomarkers; D050071:Bone Density Conservation Agents; D004337:Drug Carriers; D011208:Powders; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C028815:salmon calcitonin; D002116:Calcitonin; D002118:Calcium