title: Preparation and evaluation of icariside II-loaded binary mixed micelles using Solutol HS15 and Pluronic F127 as carriers.
abstract: An effective anti-cancer drug, icariside II (IS), has been used to treat a variety of cancers in vitro. However, its poor aqueous solubility and permeability lead to low oral bioavailability. The aim of this work was to use Solutol®HS15 and Pluronic F127 as surfactants to develop novel mixed micelles to enhance the oral bioavailability of IS by improving permeability and inhibiting efflux. The IS-loaded mixed micelles were prepared using the method of ethanol thin-film hydration. The physicochemical properties, dissolution property, oral bioavailability of the male SD rats, permeability and efflux of Caco-2 transport models, and gastrointestinal safety of the mixed micelles were evaluated. The optimized IS-loaded mixed micelles showed that at 4:1 ratio of Solutol®HS15 and Pluronic F127, the particle size was 12.88 nm with an acceptable polydispersity index of 0.172. Entrapment efficiency (94.6%) and drug loading (9.7%) contributed to the high solubility (11.7 mg/mL in water) of IS, which increased about 900-fold. The SF-IS mixed micelle release profile showed a better sustained release property than that of IS. In Caco-2 cell monolayer models, the efflux ratio dramatically decreased by 83.5%, and the relative bioavailability of the mixed micelles (AUC0-∞) compared with that of IS (AUC0-∞) was 317%, indicating potential for clinical application. In addition, a gastrointestinal safety assay also provided reliable clinical evidence for the safe use of this micelle.
authors.affiliation: a Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine , Nanjing , Jiangsu , China and.|b College of Pharmacy, Jiangsu University , Zhenjiang , Jiangsu , China.
authors.forename: Jian
authors.initials: J
authors.lastname: Hou
authors.affiliation: a Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine , Nanjing , Jiangsu , China and.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: a Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine , Nanjing , Jiangsu , China and.
authors.forename: E
authors.initials: E
authors.lastname: Sun
authors.affiliation: a Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine , Nanjing , Jiangsu , China and.|b College of Pharmacy, Jiangsu University , Zhenjiang , Jiangsu , China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.affiliation: a Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine , Nanjing , Jiangsu , China and.
authors.forename: Hong-Mei
authors.initials: HM
authors.lastname: Yan
authors.affiliation: a Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine , Nanjing , Jiangsu , China and.|b College of Pharmacy, Jiangsu University , Zhenjiang , Jiangsu , China.
authors.forename: Xiao-Bin
authors.initials: XB
authors.lastname: Jia
authors.affiliation: a Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine , Nanjing , Jiangsu , China and.
authors.forename: Zhen-Hai
authors.initials: ZH
authors.lastname: Zhang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D001682:Biological Availability; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry*; D005419:Flavonoids / Q000737:chemistry*; D006801:Humans; D008297:Male; D008823:Micelles; D010316:Particle Size; D010539:Permeability; D020442:Poloxamer / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013229:Stearic Acids / Q000737:chemistry*; D013501:Surface-Active Agents / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D005419:Flavonoids; D008823:Micelles; D013229:Stearic Acids; D013501:Surface-Active Agents; D020442:Poloxamer; C060988:baohuoside I; D011092:Polyethylene Glycols; C067028:Solutol HS 15
keywords: Caco-2 monolayer; HE staining; Icariside II; Pluronic F127; Solutol®HS15; micelles; oral bioavailability