title: Enhanced oral bioavailability and anticancer activity of novel curcumin loaded mixed micelles in human lung cancer cells.
abstract: BACKGROUND
  Curcumin has a wide range of pharmacological activities including antioxidant, anti-inflammatory, antidiabetic, antibacterial, wound healing, antiatherosclerotic, hepatoprotective and anti-carcinogenic. However, its clinical applications are limited owing to its poor aqueous solubility, multidrug pump P-gp efflux, extensive in vivo metabolism and rapid elimination due to glucuronidation/sulfation.
  
  
  OBJECTIVE
  The objective of the current work was to prepare novel curcumin loaded mixed micelles (CUR-MM) of Pluronic F-127 (PF127) and Gelucire® 44/14 (GL44) in order to enhance its oral bioavailability and cytotoxicity in human lung cancer cell line A549.
  
  
  METHODS
  3(2) Factorial design was used to assess the effect of formulation variables for optimization of mixed micelle batch.
  
  
  METHODS
  CUR-MM was prepared by a solvent evaporation method. The optimized CUR-MM was evaluated for size, entrapment efficiency (EE), in vitro curcumin release, cytotoxicity and oral bioavailability in rats.
  
  
  RESULTS
  The average size of CUR-MM was found to be around 188 ± 3 nm with an EE of about 76.45 ± 1.18% w/w. In vitro dissolution profile of CUR-MM revealed controlled release of curcumin. Additionally, CUR-MM showed significant improvement in cytotoxic activity (3-folds) and oral bioavailability (around 55-folds) of curcumin as compared to curcumin alone. Such significant improvement in cytotoxic activity and oral bioavailability of curcumin when formulated into mixed micelles could be attributed to solubilization of hydrophobic curcumin into micelle core along with P-gp inhibition effect of both, PF127 and GL44.
  
  
  CONCLUSIONS
  Thus the present work propose the formulation of mixed micelles of PF127 and GL44 which can act as promising carrier systems for hydrophobic drugs such as curcumin with significant improvement in their oral bioavailability.
authors.affiliation: Bharati Vidyapeeth Deemed University, Poona College of Pharmacy, Department of Pharmaceutics, Erandwane, Pune 411038, Maharashtra, India. Electronic address: sharvilpatil25@gmail.com.
authors.forename: Sharvil
authors.initials: S
authors.lastname: Patil
authors.affiliation: Bharati Vidyapeeth Deemed University, Poona College of Pharmacy, Department of Pharmaceutics, Erandwane, Pune 411038, Maharashtra, India.
authors.forename: Bhavana
authors.initials: B
authors.lastname: Choudhary
authors.affiliation: Bharati Vidyapeeth Deemed University, Poona College of Pharmacy, Department of Pharmaceutical Chemistry, Erandwane, Pune 411038, Maharashtra, India.
authors.forename: Atul
authors.initials: A
authors.lastname: Rathore
authors.affiliation: Bharati Vidyapeeth Deemed University, Poona College of Pharmacy, Department of Pharmaceutics, Erandwane, Pune 411038, Maharashtra, India.
authors.forename: Krishtey
authors.initials: K
authors.lastname: Roy
authors.affiliation: Bharati Vidyapeeth Deemed University, Poona College of Pharmacy, Department of Pharmaceutical Chemistry, Erandwane, Pune 411038, Maharashtra, India.
authors.forename: Kakasaheb
authors.initials: K
authors.lastname: Mahadik
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors; D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D001682:Biological Availability; D045744:Cell Line, Tumor / Q000187:drug effects; D003474:Curcumin / Q000493:pharmacokinetics / Q000494:pharmacology*; D003692:Delayed-Action Preparations / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008175:Lung Neoplasms / Q000473:pathology*; D008297:Male; D008823:Micelles; D010316:Particle Size; D020442:Poloxamer / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D008823:Micelles; D020442:Poloxamer; C104509:gelucire 44-14; D011092:Polyethylene Glycols; D003474:Curcumin
keywords: Anticancer activity; Curcumin; Mixed micelles; Oral bioavailability; Pluronic