title: Novel dietary lipid-based self-nanoemulsifying drug delivery systems of paclitaxel with p-gp inhibitor: implications on cytotoxicity and biopharmaceutical performance.
abstract: OBJECTIVE
  This work describes the development and characterization of novel self-nanoemulsifying drug delivery systems (SNEDDS) employing polyunsaturated fatty acids for enhancing the oral bioavailability and anticancer activity of paclitaxel (PTX) by coadministration with curcumin (Cu).
  
  
  METHODS
  Preformulation studies endorsed sesame oil, labrasol, and sodium deoxycholate as lipid surfactants and cosurfactants based on their solubility for the drugs and spontaneity of emulsification to produce nanoemulsions. Further, phase titration studies were performed to identify a suitable nanoemulsion region for preparing the SNEDDS formulation.
  
  
  RESULTS
  The prepared formulations were characterized through in vitro, in situ, and in vivo studies to evaluate the biopharmaceutical performance. In vitro drug release studies showed 2.8- to 3.4-fold enhancement in the dissolution rate of both drugs from SNEDDS as compared with the pure drug suspension. Cell line studies revealed 1.5- to 2.7-fold reduction in the cytotoxicity on MCF-7 cells by plain PTX-SNEDDS and PTX-Cu-SNEDDS vis-à-vis the PTX-suspension. In situ intestinal perfusion studies revealed significant augmentation in permeability and absorption parameters of drug from PTX-Cu-SNEDDS over the plain PTX-SNEDDS and PTX-suspension (p < 0.001). In vivo pharmacokinetic studies also showed a remarkable improvement (i.e., 5.8- to 6.3-fold) in the oral bioavailability (Cmax and AUC) of the drug from PTX-SNEDDS and PTX-Cu-SNEDDS vis-à-vis the PTX-suspension.
  
  
  CONCLUSIONS
  Overall, the studies corroborated superior biopharmaceutical performance of PTX-Cu-SNEDDS.
authors.affiliation: a 1 Rajeev Gandhi Technical University, School of Pharmaceutical Sciences , Bhopal, Madhya Pradesh, India pssandhu.rgtu@gmail.com.|b 2 Panjab University, UGC Centre of Excellence in Applications of Nanomaterials, Nanoparticles and Nanocomposites (Biomedical Sciences) , Chandigarh, India.
authors.forename: Premjeet Singh
authors.initials: PS
authors.lastname: Sandhu
authors.affiliation: c 3 Panjab University, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Studies , Chandigarh, India.
authors.forename: Sarwar
authors.initials: S
authors.lastname: Beg
authors.affiliation: a 1 Rajeev Gandhi Technical University, School of Pharmaceutical Sciences , Bhopal, Madhya Pradesh, India pssandhu.rgtu@gmail.com.
authors.forename: Farhad
authors.initials: F
authors.lastname: Mehta
authors.affiliation: b 2 Panjab University, UGC Centre of Excellence in Applications of Nanomaterials, Nanoparticles and Nanocomposites (Biomedical Sciences) , Chandigarh, India.|c 3 Panjab University, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Studies , Chandigarh, India.
authors.forename: Bhupinder
authors.initials: B
authors.lastname: Singh
authors.affiliation: d 4 Rajiv Gandhi Technical University, School of Pharmaceutical Sciences , Bhopal, Madhya Pradesh, India piyushtrivedi.rgtu@gmail.com.
authors.forename: Piyush
authors.initials: P
authors.lastname: Trivedi
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors*; D000818:Animals; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems; D065546:Drug Liberation; D004655:Emulsions; D006801:Humans; D008055:Lipids / Q000737:chemistry; D061986:MCF-7 Cells; D017239:Paclitaxel / Q000008:administration & dosage*; D017208:Rats, Wistar; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004655:Emulsions; D008055:Lipids; D013501:Surface-Active Agents; D017239:Paclitaxel
keywords: bioavailability; dissolution; fatty acids; hepatic first-pass; pharmacokinetics