title: Readily restoring freeze-dried probilosomes as potential nanocarriers for enhancing oral delivery of cyclosporine A.
abstract: Formulating vesicular nanocarriers into dried precursors so as to overcome the drawbacks associated with liquid formulations is challengeable due to low efficiency of restoration. In this study, bilosomes interiorly thickened with gelatin (G-BLs) was evaluated for the ability to withstand freeze-drying stress and enhanced oral bioavailability of a model drug, cyclosporine A (CyA). The restoration efficiency of freeze-dried pro-G-BLs is investigated by comparing the particle size distribution, entrapment efficiency and morphology of the bilosomes before and after freeze-drying. Particle size and polydispersity index (PI) of pro-G-BLs after restoration was similar to that before freeze-drying, whereas freeze-dried bilosomes without gelatin thickening (pro-BLs) show irreversible damage and aggregation along with significantly increased particle size and PI after restoration. Entrapment efficiency of pro-G-BLs remains as high as 83.7%, in sharp contrast with 66.7% for pro-BLs. Pharmacokinetics in beagle dogs show improved absorption of CyA in pro-G-BLs as compared to pro-BLs, G-BLs and microemulsion-based Sandimmun Neoral(®). The relative oral bioavailability of CyA-loaded pro-G-BLs, pro-BLs and G-BLs was 165.2%, 123.5% and 130.1%, respectively, with Neoral(®) as the reference. It is concluded that interior thickening with gelatin significantly enhanced the stability against freeze-drying stress, which as a result improves the restoring efficiency and oral bioavailability.
authors.affiliation: College of Life and Health Sciences, Northeastern University, 110819 Shenyang, PR China; School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery of MOE and PLA, 201203 Shanghai, PR China.
authors.forename: Peipei
authors.initials: P
authors.lastname: Guan
authors.affiliation: School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery of MOE and PLA, 201203 Shanghai, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Lu
authors.affiliation: School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery of MOE and PLA, 201203 Shanghai, PR China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Qi
authors.affiliation: School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery of MOE and PLA, 201203 Shanghai, PR China. Electronic address: wuwei@shmu.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001647:Bile Acids and Salts / Q000737:chemistry*; D001692:Biological Transport / Q000187:drug effects; D016572:Cyclosporine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004285:Dogs; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D005612:Freeze Drying; D008081:Liposomes / Q000737:chemistry*; D008196:Lymph / Q000187:drug effects / Q000378:metabolism; D008297:Male; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D017208:Rats, Wistar
chemical_list: D001647:Bile Acids and Salts; D004337:Drug Carriers; D008081:Liposomes; D016572:Cyclosporine
keywords: Bile salt; Bilosomes; Freeze-drying; Gelatin; Liposomes; Lymphatic transportation; Oral bioavailability; Probilosomes