title: In vivo pharmacokinetics and biodistribution of resveratrol-loaded solid lipid nanoparticles for brain delivery.
abstract: Resveratrol is a potent anticancer. However, because of its low half-life (<0.25 h) the molecule is difficult to achieve the therapeutic concentration at the site of action. The aim of this work was to check the brain targeting ability of glyceryl behenate-based solid lipid nanoparticles (SLN) for resveratrol. SLN were prepared by solvent evaporation technique employing high speed homogenization followed by ultrasonication. SLN were designed at varying drug-lipid ratios (1:5, 1:9, 1:10, 1:11, 1:12 and 1:15) using Tween 80 or a combination of Tween 80 and polyvinyl alcohol (PVA) as surfactants. The mean particle size and zeta potential of the optimized formulation (drug-lipid ratio of 1:10) were 248.30 ± 3.80nm and -25.49 ± 0.49mV, respectively. The particle size and the encapsulation efficiency (EE) increased when varying the drug-lipid ratio from 1:5 to 1:15. Scanning electron microscopic (SEM) analysis showed that SLN were spherical in shape and had a smooth surface. The X-ray diffraction (XRD) and differential scanning calorimetry (DSC) analyses revealed that the matrix of drug-loaded SLN was in disordered crystalline phase. The in vitro release study in phosphate buffer pH 7.4 followed a sustained release pattern. The drug release data was found to fit best into Higuchi kinetic model suggesting the diffusion controlled mechanism of drug release. The cytotoxicity assay (MAT) showed that SLN were equally effective (P<0.5) as free resveratrol, as an anti-tumor agent. The in vivo biodistribution study using Wistar rats demonstrated that SLN could significantly (P<0.001) increase the brain concentration of resveratrol (17.28 ± 0.6344 μg/g) as compared to free resveratrol (3.45 ± 0.3961 μg/g). The results showed that our resveratrol-loaded SLN serve as promising therapeutic systems to treat neoplastic diseases located in the brain tissue.
authors.affiliation: University College of Pharmacy, Mahatma Gandhi University, Cheruvandoor Campus, Ettumanoor, Kottayam 686631, Kerala, India. Electronic address: sajanjose@hotmail.com.
authors.forename: S
authors.initials: S
authors.lastname: Jose
authors.affiliation: University College of Pharmacy, Mahatma Gandhi University, Cheruvandoor Campus, Ettumanoor, Kottayam 686631, Kerala, India.
authors.forename: S S
authors.initials: SS
authors.lastname: Anju
authors.affiliation: University College of Pharmacy, Mahatma Gandhi University, Cheruvandoor Campus, Ettumanoor, Kottayam 686631, Kerala, India; Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka, India.
authors.forename: T A
authors.initials: TA
authors.lastname: Cinu
authors.affiliation: University College of Pharmacy, Mahatma Gandhi University, Cheruvandoor Campus, Ettumanoor, Kottayam 686631, Kerala, India.
authors.forename: N A
authors.initials: NA
authors.lastname: Aleykutty
authors.affiliation: Centre for Nanoscience and Nanotechnology, Mahatma Gandhi University, Kottayam, India.
authors.forename: S
authors.initials: S
authors.lastname: Thomas
authors.affiliation: Faculty of Health Sciences, Fernando Pessoa University, Rua Carlos da Maia, 296, P-4200-150 Porto, Portugal; Centre for Research in Bimedicine (CEBIMED), Fernando Pessoa University, Praça 9 de Abril, 349, P-4249-004 Porto, Portugal; Institute of Biotechnology and Bioengineering, Centre of Genomics and Biotechnology, University of Trás-os-Montes and Alto Douro, 5001-801 Vila-Real, Portugal. Electronic address: eliana@ufp.edu.pt.
authors.forename: E B
authors.initials: EB
authors.lastname: Souto
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D001921:Brain / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D007274:Injections, Intraperitoneal; D008055:Lipids / Q000008:administration & dosage* / Q000493:pharmacokinetics; D053758:Nanoparticles / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D013329:Structure-Activity Relationship; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D008055:Lipids; D013267:Stilbenes; D000077185:Resveratrol
keywords: Brain cancer; Brain targeting; Cytotoxicity; Resveratrol; Solid lipid nanoparticles (SLN)