title: Subcutaneously injected ivermectin-loaded mixed micelles: formulation, pharmacokinetics and local irritation study.
abstract: Clinical application of ivermectin (IVM) is limited by several unfavorable properties, induced by its insolubility in water. Slight differences in formulation may change the plasma pharmacokinetics and efficacy. In this study, an IVM-loaded Soy phosphatidylcholine-sodium deoxycholate mixed micelles (IVM-SPC-SDC-MMs) were developed to improve its aqueous solubility, aiming to make it more applicable for clinical use. First, IVM-SPC-SDC-MMs were prepared using the co-precipitation method. After formulation optimization, the particle size was 9.46 ± 0.16 nm according to dynamic light scattering. The water solubility of IVM in SPC-SDC-MMs (4.79 ± 0.02 mg/mL) was improved by 1200-fold, comparing with free IVM (0.004 mg/mL). After subcutaneous administration, the pharmacokinetic study showed that IVM-SPC-SDC-MMs and commercially available IVM injection were bioequivalent. Also, the local irritation study confirmed that IVM-SPC-SDC-MMs reduced side reactions of the commercially available IVM injection. These results indicated that IVM-SPC-SDC-MMs represented a promising new drug formulation suitable for subcutaneous delivery of IVM.
authors.affiliation: a Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy , Sichuan University , Sichuan , People's Republic of China.
authors.forename: Jianxia
authors.initials: J
authors.lastname: Dong
authors.affiliation: a Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy , Sichuan University , Sichuan , People's Republic of China.
authors.forename: Xu
authors.initials: X
authors.lastname: Song
authors.affiliation: a Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy , Sichuan University , Sichuan , People's Republic of China.
authors.forename: Xianghong
authors.initials: X
authors.lastname: Lian
authors.affiliation: a Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy , Sichuan University , Sichuan , People's Republic of China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Fu
authors.affiliation: a Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy , Sichuan University , Sichuan , People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Gong
mesh_terms: D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003840:Deoxycholic Acid / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry; D007279:Injections, Subcutaneous / Q000379:methods; D007559:Ivermectin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D008823:Micelles; D010316:Particle Size; D010713:Phosphatidylcholines / Q000737:chemistry; D011817:Rabbits; D012995:Solubility; D013810:Therapeutic Equivalency
chemical_list: D004337:Drug Carriers; D008823:Micelles; D010713:Phosphatidylcholines; D003840:Deoxycholic Acid; D007559:Ivermectin
keywords: Ivermectin; local irritation; mixed micelles; pharmacokinetic; soy phosphatidylcholine-sodium–deoxycholate