title: Pharmacokinetics, biodistribution, in vitro cytotoxicity and biocompatibility of Vitamin E TPGS coated trans resveratrol liposomes.
abstract: The clinical application of trans resveratrol (RSV) in glioma treatment is largely limited because of its rapid metabolism, fast elimination from systemic circulation and low biological half life. Therefore, the objectives of this study were to enhance the circulation time, biological half life and passive brain targeting of RSV using d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) coated liposomes (RSV-TPGS-Lipo). In addition to basic liposomal characterizations, in vitro anticancer potential against C6 glioma cell lines and cellular internalization of liposomes were carried out by MTT assay and confocal laser scanning microscopy (CLSM), respectively. Pharmacokinetics and tissue distribution studies were also carried out after intravenous administration in Charles Foster rats. RSV-TPGS-Lipo 2 showed significantly higher cytotoxicity than RSV-Lipo (uncoated liposomes) and RSV. Both uncoated and TPGS coated liposomes showed excellent cellular uptake. RSV, RSV-Lipo and RSV-TPGS-Lipo 2 were found to be haemocompatible and safe after i.v. administration. Area under the curve (AUC) and plasma half life (t1/2) after i.v. administration of RSV-TPGS-Lipo 2 was found to be approximately 5.73 and 6.72 times higher than that of RSV-Lipo as well as 29.94 and 29.66 times higher than that of RSV, respectively. Thus, the outcome indicates that RSV-TPGS-Lipo 2 is a promising carrier for glioma treatment with improved pharmacokinetic parameters. Moreover, brain accumulation of RSV-Lipo and RSV-TPGS-Lipo 2 was found to be significantly higher than that of RSV (P<0.05). Results are suggesting that both RSV-Lipo and RSV-TPGS-Lipo 2 are the promising tools of RSV for the treatment of brain cancer.
authors.affiliation: Department of Pharmaceutics, Indian Institute of Technology (Banaras Hindu University), Varanasi 221 005, India.
authors.forename: Mahalingam Rajamanickam
authors.initials: MR
authors.lastname: Vijayakumar
authors.affiliation: School of Biomedical Engineering, Indian Institute of Technology (Banaras Hindu University), Varanasi 221 005, India.
authors.forename: Kiran Yellappa
authors.initials: KY
authors.lastname: Vajanthri
authors.affiliation: School of Biomedical Engineering, Indian Institute of Technology (Banaras Hindu University), Varanasi 221 005, India.
authors.forename: Chelladurai Karthikeyan
authors.initials: CK
authors.lastname: Balavigneswaran
authors.affiliation: School of Biomedical Engineering, Indian Institute of Technology (Banaras Hindu University), Varanasi 221 005, India.
authors.forename: Sanjeev Kumar
authors.initials: SK
authors.lastname: Mahto
authors.affiliation: School of Biomedical Engineering, Indian Institute of Technology (Banaras Hindu University), Varanasi 221 005, India.
authors.forename: Nira
authors.initials: N
authors.lastname: Mishra
authors.affiliation: Department of Pharmaceutics, Indian Institute of Technology (Banaras Hindu University), Varanasi 221 005, India.
authors.forename: Madaswamy S
authors.initials: MS
authors.lastname: Muthu
authors.affiliation: Department of Pharmaceutics, Indian Institute of Technology (Banaras Hindu University), Varanasi 221 005, India. Electronic address: ssingh.phe@iitbhu.ac.in.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Singh
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics; D001932:Brain Neoplasms / Q000188:drug therapy; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics; D008081:Liposomes / Q000737:chemistry*; D008297:Male; D050997:Nanomedicine / Q000379:methods*; D011092:Polyethylene Glycols / Q000737:chemistry; D051381:Rats; D000077185:Resveratrol; D013267:Stilbenes / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D014810:Vitamin E / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008081:Liposomes; D013267:Stilbenes; D014810:Vitamin E; D011092:Polyethylene Glycols; C014225:tocophersolan; D000077185:Resveratrol
keywords: Cancer nanomedicine; Cell uptake of liposomes; PEGylated liposomes; Passive brain targeting; Sustained release; Trans resveratrol