title: Co-administration with cell penetrating peptide enhances the oral bioavailability of docetaxel-loaded nanoparticles.
abstract: This study proposes a novel docetaxel (DTX) cyclodextrin inclusion-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles (D-CNPs) system with cell penetrating peptide (CPP), and evaluates its potential for oral administration of DTX. Heptaarginine (R7) was used as the CPP. D-CNPs were prepared by the double-emulsification method. The mean particle size and zeta potential of the resulting D-CNPs were 198.7 ± 12.56 nm and -27.25 ± 4.62 mV, respectively, and their mean encapsulation efficiency and drug loading were 80.35 ± 6.37% and 1.02 ± 0.15%, respectively. The morphology of the D-CNPs was observed by scanning electron microscope (SEM) and transmission electron microscope (TEM). The release behavior of the D-CNPs was studied by using the dialysis method. The relative bioavailability of D-CNPs and D-CNPs co-administered with R7 was enhanced about 5.57- and 9.43-fold, respectively, compared with the free DTX suspension. Furthermore, D-CNPs with R7 displayed maximum cytotoxicity against MCF-7 cells in MTT assay. D-CNPs co-administered with R7 showed markedly higher fluorescence intensity than D-CNPs without CPP. The results suggest that the D-CNPs co-administered with R7 could be a potential delivery system with excellent therapeutic efficacy for targeting the drugs to cancer cells.
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University , Shanghai , China.
authors.forename: Xiangyuan
authors.initials: X
authors.lastname: Bu
authors.forename: Tao
authors.initials: T
authors.lastname: Zhu
authors.forename: Yiran
authors.initials: Y
authors.lastname: Ma
authors.forename: Qi
authors.initials: Q
authors.lastname: Shen
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001682:Biological Availability; D057846:Cell-Penetrating Peptides / Q000008:administration & dosage*; D000077143:Docetaxel; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D065546:Drug Liberation; D004655:Emulsions; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry; D061986:MCF-7 Cells; D008297:Male; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles; D009842:Oligopeptides / Q000008:administration & dosage; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017207:Rats, Sprague-Dawley; D043823:Taxoids / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D000970:Antineoplastic Agents; D057846:Cell-Penetrating Peptides; D004337:Drug Carriers; D004655:Emulsions; D009842:Oligopeptides; D043823:Taxoids; C416678:heptaarginine amide; D000077143:Docetaxel; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: Bioavailability; PLGA; cell penetrating peptide; cyclodextrin inclusion; docetaxel; nanoparticles