title: A combination of complexation and self-nanoemulsifying drug delivery system for enhancing oral bioavailability and anticancer efficacy of curcumin.
abstract: OBJECTIVE
  Curcumin, the golden spice from Indian saffron, has shown chemoprotective action against many types of cancer including breast cancer. However, poor oral bioavailability is the major hurdle in its clinical application. In the recent years, self-nanoemulsifying drug delivery system (SNEDDS) has emerged as a promising tool to improve the oral absorption and enhancing the bioavailability of poorly water-soluble drugs. In this context, complexation with lipid carriers like phospholipid has also shown the tremendous potential to improve the solubility and therapeutic efficacy of certain drugs with poor oral bioavailability.
  
  
  METHODS
  In the present investigation, a systematic combination of both the approaches is utilized to prepare the phospholipid complex of curcumin and facilitate its incorporation into SNEDDS. The combined use of both the approaches has been explored for the first time to enhance the oral bioavailability and in turn increase the anticancer activity of curcumin.
  
  
  RESULTS
  As evident from the pharmacokinetic studies and in situ single pass intestinal perfusion studies in Sprague-Dawley rats, the optimized SNEDDS of curcumin-phospholipid complex has shown enhanced oral absorption and bioavailability of curcumin. The cytotoxicity study in metastatic breast carcinoma cell line has shown the enhancement of cytotoxic action by 38.7%. The primary tumor growth reduction by 58.9% as compared with the control group in 4T1 tumor-bearing BALB/c mice further supported the theory of enhancement of anticancer activity of curcumin in SNEDDS.
  
  
  CONCLUSIONS
  The developed formulation can be a potential and safe carrier for the oral delivery of curcumin.
authors.affiliation: a Pharmacokinetics & Metabolism Division , CSIR-Central Drug Research Institute , Lucknow , India.|b Academy of Scientific and Innovative Research , New Delhi , India.
authors.forename: Mahendra
authors.initials: M
authors.lastname: Shukla
authors.affiliation: a Pharmacokinetics & Metabolism Division , CSIR-Central Drug Research Institute , Lucknow , India.|b Academy of Scientific and Innovative Research , New Delhi , India.
authors.forename: Swati
authors.initials: S
authors.lastname: Jaiswal
authors.affiliation: a Pharmacokinetics & Metabolism Division , CSIR-Central Drug Research Institute , Lucknow , India.|b Academy of Scientific and Innovative Research , New Delhi , India.
authors.forename: Abhisheak
authors.initials: A
authors.lastname: Sharma
authors.affiliation: c Medicinal & Process Chemistry Division , CSIR-Central Drug Research Institute , Lucknow , India.
authors.forename: Pradeep Kumar
authors.initials: PK
authors.lastname: Srivastava
authors.affiliation: b Academy of Scientific and Innovative Research , New Delhi , India.|d Pharmaceutics Division , CSIR-Central Drug Research Institute , Lucknow , India.
authors.forename: Abhishek
authors.initials: A
authors.lastname: Arya
authors.affiliation: b Academy of Scientific and Innovative Research , New Delhi , India.|d Pharmaceutics Division , CSIR-Central Drug Research Institute , Lucknow , India.
authors.forename: Anil Kumar
authors.initials: AK
authors.lastname: Dwivedi
authors.affiliation: a Pharmacokinetics & Metabolism Division , CSIR-Central Drug Research Institute , Lucknow , India.|b Academy of Scientific and Innovative Research , New Delhi , India.
authors.forename: Jawahar
authors.initials: J
authors.lastname: Lal
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003474:Curcumin / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods; D065546:Drug Liberation / Q000187:drug effects; D004655:Emulsions / Q000737:chemistry*; D008297:Male; D053758:Nanoparticles / Q000737:chemistry; D010316:Particle Size; D010743:Phospholipids / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility / Q000187:drug effects; D013501:Surface-Active Agents / Q000737:chemistry; D014867:Water / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D004655:Emulsions; D010743:Phospholipids; D013501:Surface-Active Agents; D014867:Water; D011092:Polyethylene Glycols; D003474:Curcumin
keywords: Box–Behnken design; LC-MS/MS; Pharmacokinetics; bioavailability; nanoemulsion