title: A novel folate-modified self-microemulsifying drug delivery system of curcumin for colon targeting.
abstract: BACKGROUND
  The objective of this study was to prepare, characterize, and evaluate a folate-modified self-microemulsifying drug delivery system (FSMEDDS) with the aim to improve the solubility of curcumin and its delivery to the colon, facilitating endocytosis of FSMEDDS mediated by folate receptors on colon cancer cells.
  
  
  METHODS
  Ternary phase diagrams were constructed in order to obtain the most efficient self-emulsification region, and the formulation of curcumin-loaded SMEDDS was optimized by a simplex lattice experiment design. Then, three lipophilic folate derivatives (folate-polyethylene glycol-distearoylphosphatidylethanolamine, folate-polyethylene glycol-cholesteryl hemisuccinate, and folate-polyethylene glycol-cholesterol) used as a surfactant were added to curcumin-loaded SMEDDS formulations. An in situ colon perfusion method in rats was used to optimize the formulation of FSMEDDS. Curcumin-loaded FSMEDDS was then filled into colon-targeted capsules and the in vitro release was investigated. Cytotoxicity studies and cellular uptake studies was used in this research.
  
  
  RESULTS
  The optimal formulation of FSMEDDS obtained with the established in situ colon perfusion method in rats was comprised of 57.5% Cremophor(®) EL, 32.5% Transcutol(®) HP, 10% Capryol™ 90, and a small amount of folate-polyethylene glycol-cholesteryl hemisuccinate (the weight ratio of folate materials to Cremophor EL was 1:100). The in vitro release results indicated that the obtained formulation of curcumin could reach the colon efficiently and release the drug immediately. Cellular uptake studies analyzed with fluorescence microscopy and flow cytometry indicated that the FSMEDDS formulation could efficiently bind with the folate receptors on the surface of positive folate receptors cell lines. In addition, FSMEDDS showed greater cytotoxicity than SMEDDS in the above two cells.
  
  
  CONCLUSIONS
  FSMEDDS-filled colon-targeted capsules are a potential carrier for colon delivery of curcumin.
authors.affiliation: Department of Pharmaceutical Engineering, College of Pharmacy, Shandong University, Jinan, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.forename: Weiwei
authors.initials: W
authors.lastname: Zhu
authors.forename: Chunfen
authors.initials: C
authors.lastname: Yang
authors.forename: Hongxia
authors.initials: H
authors.lastname: Guo
authors.forename: Aihua
authors.initials: A
authors.lastname: Yu
authors.forename: Jianbo
authors.initials: J
authors.lastname: Ji
authors.forename: Yan
authors.initials: Y
authors.lastname: Gao
authors.forename: Min
authors.initials: M
authors.lastname: Sun
authors.forename: Guangxi
authors.initials: G
authors.lastname: Zhai
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D002470:Cell Survival / Q000187:drug effects; D003106:Colon / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D003474:Curcumin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods*; D004655:Emulsions / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D005434:Flow Cytometry; D005492:Folic Acid / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D019073:HT29 Cells; D006367:HeLa Cells; D006801:Humans; D051381:Rats; D012995:Solubility; D013501:Surface-Active Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D000970:Antineoplastic Agents; D004655:Emulsions; D013501:Surface-Active Agents; D005492:Folic Acid; D003474:Curcumin