Contents lists available at ScienceDirect Journal of Drug Delivery Science and Technology journal homepage: www.elsevier.com/locate/jddst Self-nanoemulsifying drug delivery system of fsetin: Formulation, optimization, characterization and cytotoxicity assessment Rajan Kumar a , Rubiya Khursheed a , Rakesh Kumar a , Ankit Awasthi a , Neha Sharma a , Shelly Khurana b , Bhupinder Kapoor a , Navneet Khurana a , Sachin Kumar Singh a,∗ , Kuppusamy Gowthamarajan c , Ashish Wadhwani d a School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, 144411, India b Department of Pharmacy, Govt. Polytechnic College, Amritsar, India c Department of Pharmaceutics, J.S.S. College of Pharmacy, JSS Academy of Higher Education and Research, Ootacamund, Tamilnadu, India d Department of Pharmaceutical Biotechnology, J.S.S. College of Pharmacy, JSS Academy of Higher Education and Research, Ootacamund, Tamilnadu, India ARTICLE INFO Keywords: Fisetin SNEDDS Permeation Dissolution Box-Behnken design ABSTRACT Fisetin is a plant derived favonoid that possesses anti-cancer, anti-oxidant and anti-Parkinson's activities. However, due to its lipophilicity it sufers from dissolution rate limited oral bioavailability that reduces its therapeutic efcacy. In order to overcome this issue self-nanoemulsifying drug delivery system (SNEDDS) of fsetin were formulated and characterized for droplet size, shape, zeta potential, cell viability, dissolution and permeability studies. Prepared SNEDDS (1.2 mL) were composed of castor oil (0.1 mL), Lauroglycol FCC (0.1 mL), tween 80 (0.4 mL), Transcutol P (0.6 mL) and fsetin (5 mg). The formulation was optimized using Box Behnken Design. Droplet size and zeta potential of optimized SNEDDS were found to be 154 nm and −37 mV. Dissolution rate of fsetin got signifcantly (p < 0.05) enhanced through SNEDDS formulation in all the media as compared to unprocessed fsetin. Toxicity studies revealed more cell viability (89.05%) for fsetin loaded in SNEDDS as compared to its unprocessed form (10.8%) at a fxed concentration (62.5 μg/mL). The in-vitro cell line study revealed about 3.79 folds increase in permeation rate for fsetin loaded in SNEDDS. The developed formulation was found to be stable with change in temperature, dilution and pH. The study entailed successful formulation of SNEDDS loaded with fsetin. 1. Introduction Fisetin (3,3′, 4′7-tetrahydroxyfavone) is one of the favonoids that belongs to the category of favanol. The chemical structure of fsetin is shown in Fig. 1. It is present in various fruits and vegetables and the highest concentration is reported in strawberries (160 μg/g) followed by apple (26.9μg/g) and persimmons (10.5μg/g) [1]. It possesses pharmacological activities like antioxidant, anti-infammatory, hypoli- pidemic, anti-adipocyte diferentiation, inhibition of allergic airway infammation [2–5] neurotropic activity [6], anti-cancer [7,8] and anti- depressant [9]. Patel et al. (2012), reported neuroprotective efect of fsetin on MPTP/MPP + - (1-methyl-4-phenyl-1, 2, 3, 6-tetra- hydropyridine/1-methyl-4-phenylpyridinium) induced neurotoxicity in PC12 cells to treat Parkinson's disease [10]. Despite having various pharmacological properties, fsetin possesses low aqueous solubility and oral bioavailability [11,12]. There is no much literature available related to formulation strategies adopted to improve dissolution rate, permeation and oral bioavailability of fsetin. Nanotechnology has a great impact on pharmaceutical science and continuous work is going on to evaluate its impact on other branches of the pharmaceutical sciences. The ultimate aim of using nanotechnology in pharmaceutics is to improve the bioavailability, reducing the side efects of drug which ultimately improves their therapeutic potential. The various ways by which nanotechnology imparts its impact in pharmaceutics are solubilizing the hydrophobic drugs, enhancing per- meation of poorly soluble drugs, regulating the biodistribution, en- abling/improving target delivery and protecting drugs from degrada- tion. Various types of nanocarriers like lipid based nanocarrier, inorganic nanocarrier, polymeric nanocarrier and drug nanoparticle are currently being used. The lipid based nanocarriers are further divided as lipid core micelles, liposomes, microemulsion, nanoemulsion, solid lipid nanoparticle and nanostructured lipid carriers [13,14]. Self nano emulsifying drug delivery system (SNEDDS) are thermodynamically stable systems that have been extensively explored to improve https://doi.org/10.1016/j.jddst.2019.101252 Received 18 May 2019; Received in revised form 15 August 2019; Accepted 2 September 2019 ∗ Corresponding author. School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, 144411, Punjab, India. E-mail addresses: singhsachin23@gmail.com, sachin.16030@lpu.co.in, sachin_pharma06@yahoo.co.in (S.K. Singh). Journal of Drug Delivery Science and Technology 54 (2019) 101252 Available online 05 September 2019 1773-2247/ © 2019 Elsevier B.V. All rights reserved. T