title: α-Tocopherol as functional excipient for resveratrol and coenzyme Q10-loaded SNEDDS for improved bioavailability and prophylaxis of breast cancer.
abstract: The present study evaluates the prophylactic efficacy of α-tocopherol (α-TOH), resveratrol (RES), and coenzyme Q10 (CoQ10) co-loaded self-nanoemulsifying drug delivery system (α-TOH-RES-CoQ10 SNEDDS) in 7,12-Dimethylbenz[a]anthracene (DMBA) induced breast cancer model. SNEDDS formulation components were rationally selected and optimized for maximum drug loading by applying the design of experiments and further evaluated for stability in simulated gastrointestinal fluids, functional stability of antioxidants, in vitro release, Caco-2 cell uptake, oral bioavailability and prophylactic anticancer activity. The SNEDDS demonstrated excellent stability in stimulated gastrointestinal fluids. The functional activity of antioxidants was confirmed by 2,2-diphenylpicrylhydrazyl (DPPH) scavenging assay wherein significantly (p > .05) higher antioxidant activity was observed in case of SNEDDS as compared with free antioxidants. Coumarin 6 (C-6)-loaded SNEDDS formulation demonstrated remarkably higher Caco-2 cell uptake in comparison with free C-6, indicative of efficient internalization of sub-micron SNEDDS droplets by Caco-2 cells. In line with Caco-2 cell uptake observations, α-TOH-RES-CoQ10-SNEDDS showed ∼2.30- and ∼3.64-fold increase in the AUC0-∞values of RES and CoQ10 in comparison with free antioxidants. Significantly lower (p < .001) tumor volume (∼327 mm3) was found in case of animals treated with α-TOH-RES-CoQ10-SNEDDS in comparison with free antioxidant combination (∼1070 mm3) and DMBA control (∼1540 mm3) groups. Conclusively, the proposed strategy posed great potential in improving the prophylactic activity of antioxidants and hold promise for further exploration.
authors.affiliation: a Department of Pharmaceutics, Centre for Pharmaceutical Nanotechnology , National Institute of Pharmaceutical Education and Research , Punjab , India.
authors.forename: Sanyog
authors.initials: S
authors.lastname: Jain
authors.affiliation: a Department of Pharmaceutics, Centre for Pharmaceutical Nanotechnology , National Institute of Pharmaceutical Education and Research , Punjab , India.
authors.forename: Tanya
authors.initials: T
authors.lastname: Garg
authors.affiliation: a Department of Pharmaceutics, Centre for Pharmaceutical Nanotechnology , National Institute of Pharmaceutical Education and Research , Punjab , India.
authors.forename: Varun
authors.initials: V
authors.lastname: Kushwah
authors.affiliation: a Department of Pharmaceutics, Centre for Pharmaceutical Nanotechnology , National Institute of Pharmaceutical Education and Research , Punjab , India.
authors.forename: Kaushik
authors.initials: K
authors.lastname: Thanki
authors.affiliation: a Department of Pharmaceutics, Centre for Pharmaceutical Nanotechnology , National Institute of Pharmaceutical Education and Research , Punjab , India.|b James Graham Brown Cancer Center , University of Louisville , Louisville , KY , USA.
authors.forename: Ashish Kumar
authors.initials: AK
authors.lastname: Agrawal
authors.affiliation: a Department of Pharmaceutics, Centre for Pharmaceutical Nanotechnology , National Institute of Pharmaceutical Education and Research , Punjab , India.
authors.forename: Chander Parkash
authors.initials: CP
authors.lastname: Dora
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000493:pharmacokinetics; D019540:Area Under Curve; D001682:Biological Availability; D001943:Breast Neoplasms / Q000517:prevention & control*; D018938:Caco-2 Cells; D003374:Coumarins / Q000008:administration & dosage / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D004655:Emulsions; D005079:Excipients / Q000737:chemistry; D005260:Female; D006801:Humans; D053758:Nanoparticles; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage* / Q000493:pharmacokinetics; D013844:Thiazoles / Q000008:administration & dosage / Q000493:pharmacokinetics; D014451:Ubiquinone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D024502:alpha-Tocopherol / Q000737:chemistry*
chemical_list: D000975:Antioxidants; D003374:Coumarins; D004655:Emulsions; D005079:Excipients; D013267:Stilbenes; D013844:Thiazoles; C517282:coumarin 6; D014451:Ubiquinone; C024989:coenzyme Q10; D024502:alpha-Tocopherol; D000077185:Resveratrol
keywords: Chemoprevention; Coenzyme Q10; Functional excipient; Resveratrol; SNEDDS; α-Tocopherol