title: Pharmacokinetic, biodistribution and therapeutic efficacy of 5-fluorouracil-loaded pH-sensitive PEGylated liposomal nanoparticles in HCT-116 tumor bearing mouse.
abstract: The objective of the study was to investigate the pharmacokinetics and efficacy of 5-FU entrapped pH-sensitive liposomal nanoparticles with surface-modified anti-epidermal growth factor receptor (EGFR) antibody (pHLNps-5-FU) delivery system. Cytotoxicity of 5-FU and pHLNps-5-FU was determined in vitro against HCT-116 cells. The biodistribution and pharmacokinetic parameters of the administered 5-FU and pHLNps-5-FU as well as efficacy of 5-FU and pHLNps-5-FU were determined in HCT-116 subcutaneous mouse model. Mean size of pHLNp-5-FU was 164.3 ± 8.4 nm with entrapment efficiency (E.E) of 54.17%. While cytotoxicity of 5-FU and pHLNps-5-FU showed a strong dose-dependent, pHLNps-5-FU proved to be more effective (2-3 fold high) than that of 5-FU against HCT-116 cells. Pharmacokinetic study showed a prolonged plasma circulation of pHLNps-5-FU and a more significant body exposure while accumulation of pHLNps-5-FU in tumor was significantly higher than that of free 5-FU. Further, the efficacy of pHLNps-5-FU, was greater than free 5-FU at equivalent 5-FU dose. The study suggests that pHLNps may be an effective drug delivery system to enhance the anticancer activity of 5-FU against colorectal tumor growth.
authors.affiliation: Division of Basic Sciences, College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, Florida, USA.
authors.forename: Ofonime
authors.initials: O
authors.lastname: Udofot
authors.affiliation: Division of Basic Sciences, College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, Florida, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Affram
authors.affiliation: Division of Basic Sciences, College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, Florida, USA.
authors.forename: Taylor
authors.initials: T
authors.lastname: Smith
authors.affiliation: Division of Basic Sciences, College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, Florida, USA.
authors.forename: Bulumko
authors.initials: B
authors.lastname: Tshabe
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Sunil
authors.initials: S
authors.lastname: Krishnan
authors.affiliation: Division of Basic Sciences, College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, Florida, USA.
authors.forename: Mandip
authors.initials: M
authors.lastname: Sachdeva
authors.affiliation: Division of Basic Sciences, College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, Florida, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Agyare
keywords: 5-FU; Colorectal cancer; Nanoparticles; liposomes; pharmacokinetics