title: Pulmonary liposomal formulations encapsulated procaterol hydrochloride by a remote loading method achieve sustained release and extended pharmacological effects.
abstract: Drug inhalation provides localized drug therapy for respiratory diseases. However, the therapeutic efficacy of inhaled drugs is limited by rapid clearance from the lungs. Small hydrophilic compounds have short half-lives to systemic absorption. We developed a liposomal formulation as a sustained-release strategy for pulmonary delivery of procaterol hydrochloride (PRO), a short-acting pulmonary β2-agonist for asthma treatment. After PRO-loaded liposomes were prepared using a pH gradient (remote loading) method, 100-nm liposomes improved residence times of PRO in the lungs. PRO encapsulation efficiency and release profiles were examined by screening several liposomal formulations of lipid, cholesterol, and inner phase. Although PRO loading was not achieved using the conventional hydration method, PRO encapsulation efficiency was >60% using the pH gradient method. PRO release from liposomes was sustained for several hours depending on liposomal composition. The liposomal formulation effects on the PRO behavior in rat lungs were evaluated following pulmonary administration in vivo. Sustained PRO release was achieved using simplified egg phosphatidylcholine (EPC)/cholesterol (8/1) liposome in vitro, and greater PRO remnants were observed in rat lungs following pulmonary administration. Extended pharmacological PRO effects were observed for 120min in a histamine-induced bronchoconstriction guinea pig model. We indicated the simplified EPC/cholesterol liposome potential as a controlled-release PRO carrier for pulmonary administration.
authors.affiliation: Laboratory of Pharmaceutical Engineering, Gifu Pharmaceutical University, 1-25-4 Daigaku-Nishi, Gifu 501-1196, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Tahara
authors.affiliation: Laboratory of Pharmaceutical Engineering, Gifu Pharmaceutical University, 1-25-4 Daigaku-Nishi, Gifu 501-1196, Japan.
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Tomida
authors.affiliation: Laboratory of Pharmaceutical Engineering, Gifu Pharmaceutical University, 1-25-4 Daigaku-Nishi, Gifu 501-1196, Japan.
authors.forename: Yousuke
authors.initials: Y
authors.lastname: Ito
authors.affiliation: Laboratory of Pharmaceutical Engineering, Gifu Pharmaceutical University, 1-25-4 Daigaku-Nishi, Gifu 501-1196, Japan.
authors.forename: Suguru
authors.initials: S
authors.lastname: Tachikawa
authors.affiliation: Laboratory of Pharmaceutical Engineering, Gifu Pharmaceutical University, 1-25-4 Daigaku-Nishi, Gifu 501-1196, Japan.
authors.forename: Risako
authors.initials: R
authors.lastname: Onodera
authors.affiliation: Laboratory of Pharmacology, Department of Bioactive Molecules, Gifu Pharmaceutical University, Japan; Medical Information Sciences Division, United Graduated School of Drug Discovery and Medical Information Sciences, Gifu University, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tanaka
authors.affiliation: Laboratory of Formulation Design and Pharmaceutical Technology, Osaka University of Pharmaceutical Sciences, Osaka, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Tozuka
authors.affiliation: Laboratory of Pharmaceutical Engineering, Gifu Pharmaceutical University, 1-25-4 Daigaku-Nishi, Gifu 501-1196, Japan. Electronic address: takeuchi@gifu-pu.ac.jp.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Takeuchi
mesh_terms: D000280:Administration, Inhalation; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002784:Cholesterol / Q000737:chemistry; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D006168:Guinea Pigs; D006632:Histamine / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes; D008168:Lung / Q000378:metabolism*; D008297:Male; D010316:Particle Size; D017265:Procaterol / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D003692:Delayed-Action Preparations; D008055:Lipids; D008081:Liposomes; D006632:Histamine; D002784:Cholesterol; D017265:Procaterol
keywords: Liposome; Lung; Procaterol hydrochloride; Pulmonary administration; Sustained release