title: Triple antioxidant SNEDDS formulation with enhanced oral bioavailability: Implication of chemoprevention of breast cancer.
abstract: The present study aimed to develop quercetin, resveratrol and genistein loaded self-nanoemulsifying drug delivery system (SNEDDS) by QbD approach in order to improve their oral bioavailability and antioxidant potential. The size and PDI of the optimized formulation were found to be <200nm and <0.3, respectively. DPPH scavenging assay showed comparable antioxidant activity of antioxidant loaded SNEDDS to free antioxidants combination. Furthermore, coumarin-6 loaded SNEDDS formulation showed rapid internalization within 1h of incubation by Caco-2 cells. Moreover, the pharmacokinetic studies in rats for the optimized formulation and free antioxidant suspension were performed. SNEDDS have significantly increased the Cmax and area under curve (AUC) of all three antioxidants. The SNEDDS demonstrated ~4.27 fold enhancement in oral bioavailability of quercetin, ~1.5 fold in case of resveratrol and ~2.8 fold in case of genistein as compared to free antioxidants suspension. Finally, the prophylactic antitumor efficacy of developed formulation was tested against DMBA induced breast cancer model in rats, which demonstrated enhanced abeyance towards the tumor growth as compared to free antioxidants.
authors.affiliation: Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, SAS Nagar, Punjab, India.
authors.forename: Shailja
authors.initials: S
authors.lastname: Tripathi
authors.affiliation: Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, SAS Nagar, Punjab, India.
authors.forename: Varun
authors.initials: V
authors.lastname: Kushwah
authors.affiliation: Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, SAS Nagar, Punjab, India.
authors.forename: Kaushik
authors.initials: K
authors.lastname: Thanki
authors.affiliation: Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, SAS Nagar, Punjab, India. Electronic address: sanyogjain@niper.ac.in.
authors.forename: Sanyog
authors.initials: S
authors.lastname: Jain
mesh_terms: D000818:Animals; D001682:Biological Availability; D001943:Breast Neoplasms / Q000517:prevention & control*; D018938:Caco-2 Cells; D018890:Chemoprevention; D016503:Drug Delivery Systems / Q000379:methods*; D004655:Emulsions; D005260:Female; D006801:Humans; D051381:Rats; D012995:Solubility
chemical_list: D004655:Emulsions
keywords: Chemoprevention; Genistein; Quercetin; Resveratrol; SNEDDS