title: Sirolimus-loaded polymeric micelles with honokiol for oral delivery.
abstract: OBJECTIVE
  The aims of the present study were to design polymeric micelles loading sirolimus with honokiol to increase drug solubility and to gain an insight into the effect of honokiol on oral transport of P-glycoprotein substrate (P-gp).
  
  
  METHODS
  Particle size distribution, encapsulation efficiency, drug-loading content and in-vitro release of sirolimus-loaded micelles with honokiol were determined. Transport of sirolimus-loaded micelles across Caco-2 cell monolayers and jejunum segment of rats were investigated. In-vitro cytotoxicity experiments and the cellular uptake study were carried out via sulforhodamine B assay and flow cytometry, respectively.
  
  
  RESULTS
  A coadministration of honokiol with sirolimus in micelles did not significantly modify the particle size, polydispersity index and release of drugs demonstrating successful loading within the micelles. The apparent transport coefficients (Papp ) and effective permeability (Peff ) of sirolimus were increased with more amount of honokiol loaded in micelles. Cellular uptake study demonstrated that rhodamine123 uptake rate was enhanced by honokiol-loaded micelles, indicating substantial P-gp inhibition action by honokiol and mPEG-PLA-based micelles.
  
  
  CONCLUSIONS
  Oral transport of sirolimus was significantly improved by coadministration with honokiol, an inhibitor of the P-gp, in polymeric micelles formulation.
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, China.|Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing, China.
authors.forename: Xinru
authors.initials: X
authors.lastname: Li
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China.
authors.forename: Xucheng
authors.initials: X
authors.lastname: Hou
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China.
authors.forename: Weiming
authors.initials: W
authors.lastname: Ding
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, China.
authors.forename: Shuangchen
authors.initials: S
authors.lastname: Cong
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, China.
authors.forename: Mengmeng
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, China.
authors.forename: Yansha
authors.initials: Y
authors.lastname: Meng
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, China.
authors.forename: Jiongxi
authors.initials: J
authors.lastname: Lei
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China.
authors.forename: Guiling
authors.initials: G
authors.lastname: Li
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000037:antagonists & inhibitors / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D001713:Biphenyl Compounds / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004355:Drug Stability; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D017705:Lignans / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D008297:Male; D008823:Micelles; D010316:Particle Size; D010539:Permeability; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D017207:Rats, Sprague-Dawley; D020123:Sirolimus / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D012995:Solubility; D000498:Allyl Compounds; D010636:Phenols
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D001713:Biphenyl Compounds; D004337:Drug Carriers; D017705:Lignans; D008823:Micelles; D011091:Polyesters; D011092:Polyethylene Glycols; D020123:Sirolimus; C513055:ABCB1 protein, human; C492425:methoxy poly(ethylene glycol)-poly(lactide); C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols
keywords: honokiol; oral delivery; polymeric micelle; sirolimus; transport