title: Pluronic F127-modified liposome-containing tacrolimus-cyclodextrin inclusion complexes: improved solubility, cellular uptake and intestinal penetration.
abstract: OBJECTIVE
  The aim of this study was to investigate Pluronic F127-modified liposome-containing cyclodextrin (CD) inclusion complex (FLIC) for improving the solubility, cellular uptake and intestinal penetration of tacrolimus (FK 506) in the gastrointestinal (GI) tract.
  
  
  METHODS
  Molecular modelling was performed to screen the optimal CD for the solubilization of FK 506. FLIC was prepared by thin-lipid film hydration with the inclusion complex solutions followed by membrane extrusion. Dilution tests were conducted in simulated gastric fluids and phosphate-buffered solution of sodium taurocholate to investigate the solubility improvement of FK506. The cellular uptake of nanocarriers was studied in Caco-2 cells, and intestinal mucous membrane penetration in the GI tract was evaluated in Sprague-Dawley rats.
  
  
  RESULTS
  The results showed that β-CD had the strongest binding energy with the guest molecule among the CDs. The prepared FLIC has an average diameter of 180.8 ± 8.1 nm with a spherical shape. The solubility and cellular uptake of FK 506 was greatly improved by the incorporation of CD complexes in the Pluronic F127-modified liposomes. Intestinal mucous membrane penetration was also significantly improved by the preparation of FLIC.
  
  
  CONCLUSIONS
  With improved drug solubility and intestinal mucous membrane penetration, FLIC shows a promising oral delivery system for FK 506.
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Quanlei
authors.initials: Q
authors.lastname: Zhu
authors.forename: Tao
authors.initials: T
authors.lastname: Guo
authors.forename: Dengning
authors.initials: D
authors.lastname: Xia
authors.forename: Xiuying
authors.initials: X
authors.lastname: Li
authors.forename: Chunliu
authors.initials: C
authors.lastname: Zhu
authors.forename: Haiyan
authors.initials: H
authors.lastname: Li
authors.forename: Defang
authors.initials: D
authors.lastname: Ouyang
authors.forename: Jiwen
authors.initials: J
authors.lastname: Zhang
authors.forename: Yong
authors.initials: Y
authors.lastname: Gan
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism*; D008081:Liposomes; D008297:Male; D008958:Models, Molecular; D020442:Poloxamer / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D016559:Tacrolimus / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D004337:Drug Carriers; D007166:Immunosuppressive Agents; D008081:Liposomes; D047392:beta-Cyclodextrins; D020442:Poloxamer; D016559:Tacrolimus
keywords: Pluronic F127-modified liposomes; cellular uptake; cyclodextrin inclusion complex; molecular modelling; solubility; tacrolimus