title: Preparation and in-vitro/in-vivo characterization of trans-resveratrol nanocrystals for oral administration.
abstract: Trans -resveratrol (t-RES) is a natural polyphenolic compound with extensive therapeutic activities; however, its clinical application is circumscribed due to its poor solubility and low bioavailability. The purpose of this study was to prepare stable t-RES nanocrystals (t-RES-NCs) with different stabilizers to improve its oral bioavailability. t-RES-NCs were fabricated by the probe sonication method and optimized by particles size, poly dispersive index and zeta potential. The pharmaceutical characterization of t-RES-NCs was further performed systematically. The in vitro cellular efficacy and in vivo pharmacokinetics of t-RES-NCs were also evaluated. The optimized NCs were successfully accomplished in a sub-micron particle size (110.28 ± 12.55 nm) with high ζ-potential (-32.96 ± 3.85 mV) value. Scanning electron microscopy (SEM) image indicated that morphology of t-RES-NCs was regular and rod like in shape. Meanwhile, the result of in vitro cellular efficacy against MDA-MB-231 cells revealed that developed t-RES-NCs were more efficacious and potent (p < 0.05) than plain t-RES. Compared to plain t-RES, t-RES-NCs exhibited significant increase (p < 0.05) in AUC0-t(3.5-folds) and Cmax(2.2-folds), demonstrating improved oral bioavailability of t-RES after grafting as NCs. The significant increase in oral bioavailability of developed t-RES-NCs represents an ideal vehicle for oral delivery of t-RES which ultimately reflected the clinical efficacy of t-RES.
authors.affiliation: Pharmacokinetics and Metabolism Division, CSIR-Central Drug Research Institute, Sitapur Road, Lucknow, 226031, India.
authors.forename: Sandeep K
authors.initials: SK
authors.lastname: Singh
authors.affiliation: National Institute of Pharmaceutical Education and Research, Raebareli, India.
authors.forename: Vishal
authors.initials: V
authors.lastname: Makadia
authors.affiliation: Pharmaceutics Division, CSIR-Central Drug Research Institute, Lucknow, 226031, India.
authors.forename: Shweta
authors.initials: S
authors.lastname: Sharma
authors.affiliation: Pharmacokinetics and Metabolism Division, CSIR-Central Drug Research Institute, Sitapur Road, Lucknow, 226031, India.
authors.forename: Mamunur
authors.initials: M
authors.lastname: Rashid
authors.affiliation: Pharmacokinetics and Metabolism Division, CSIR-Central Drug Research Institute, Sitapur Road, Lucknow, 226031, India.
authors.forename: Sudhir
authors.initials: S
authors.lastname: Shahi
authors.affiliation: Pharmaceutics Division, CSIR-Central Drug Research Institute, Lucknow, 226031, India.
authors.forename: Prabhat R
authors.initials: PR
authors.lastname: Mishra
authors.affiliation: Pharmacokinetics and Metabolism Division, CSIR-Central Drug Research Institute, Sitapur Road, Lucknow, 226031, India.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Wahajuddin
authors.affiliation: Pharmacokinetics and Metabolism Division, CSIR-Central Drug Research Institute, Sitapur Road, Lucknow, 226031, India. jr.gayen@cdri.res.in.
authors.forename: Jiaur R
authors.initials: JR
authors.lastname: Gayen
mesh_terms: D000284:Administration, Oral; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D065546:Drug Liberation; D004355:Drug Stability; D006801:Humans; D054709:Lecithins / Q000008:administration & dosage / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry / Q000648:ultrastructure; D010316:Particle Size; D020442:Poloxamer / Q000008:administration & dosage / Q000737:chemistry; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D014810:Vitamin E / Q000008:administration & dosage / Q000737:chemistry
chemical_list: D054709:Lecithins; D013267:Stilbenes; D020442:Poloxamer; D014810:Vitamin E; C014225:tocophersolan; D000077185:Resveratrol
keywords: Bioavailability; Chemotherapeutics; MDA-MB-231 cell lines; Nanocrystals; Trans-resveratrol