title: Polyglutamic acid-PEG nanocapsules as long circulating carriers for the delivery of docetaxel.
abstract: Recently we reported for the first time a new type of nanocapsules consisting of an oily core and a polymer shell made of a polyglutamic acid-polyethylene glycol (PEG-PGA) grafted copolymer with a 24% w/w PEG content. The goal of the work presented here has been to develop a new version of these nanocapsules, in which the shell is made of a di-block PEG-PGA copolymer with a 57% w/w PEG content and to evaluate their potential for improving the biodistribution and pharmacokinetics of the anticancer drug docetaxel (DCX). A comparative analysis of the biodistribution of fluorescently labeled PGA-PEG nanocapsules versus PGA nanocapsules or a control nanoemulsion (containing the same oil than the nanocapsules) showed that the nanocapsules, and in particular PEGylated nanocapsules, have significantly higher half-life, MRT (Mean Residence Time) and AUC (Area under the Curve) than the nanoemulsion. On a separate set of experiments, PGA-PEG nanocapsules were loaded with DCX and their antitumor efficacy was evaluated in a xenograft U87MG glioma mouse model. The results showed that the survival rate for mice treated with DCX-loaded nanocapsules was significantly increased over the control Taxotere®, while the antitumoral effect of both formulations was comparable (60% tumor growth inhibition with respect to the untreated mice). These results highlight the potential use of these novel nanocapsules as a new drug delivery platform in cancer therapy.
authors: Department of Pharmaceutics and Pharmaceutical Technology, School of Pharmacy, Campus Vida, University of Santiago de Compostela, Santiago de Compostela, Spain; Center for Research in Molecular Medicine and Chronic Diseases (CIMUS) Campus Vida, University of Santiago de Compostela, Santiago de Compostela, Spain.
authors: Giovanna
authors: G
authors: Lollo
authors: Department of Pharmaceutics and Pharmaceutical Technology, School of Pharmacy, Campus Vida, University of Santiago de Compostela, Santiago de Compostela, Spain; Center for Research in Molecular Medicine and Chronic Diseases (CIMUS) Campus Vida, University of Santiago de Compostela, Santiago de Compostela, Spain.
authors: Gustavo R
authors: GR
authors: Rivera-Rodriguez
authors: INSERM U1066, MINT - Micro et Nanomédecines biomimétiques, IBS-CHU Angers, LUNAM Université, Université d'Angers, Angers, France.
authors: Jerome
authors: J
authors: Bejaud
authors: INSERM U1078, Université de Bretagne Occidentale, Faculté de médecine, Brest cedex, France; CHRU de Brest, Brest, France.
authors: Tristan
authors: T
authors: Montier
authors: INSERM U1066, MINT - Micro et Nanomédecines biomimétiques, IBS-CHU Angers, LUNAM Université, Université d'Angers, Angers, France.
authors: Catherine
authors: C
authors: Passirani
authors: INSERM U1066, MINT - Micro et Nanomédecines biomimétiques, IBS-CHU Angers, LUNAM Université, Université d'Angers, Angers, France.
authors: Jean-Pierre
authors: JP
authors: Benoit
authors: Department of Pharmaceutics and Pharmaceutical Technology, School of Pharmacy, Campus Vida, University of Santiago de Compostela, Santiago de Compostela, Spain; Center for Research in Molecular Medicine and Chronic Diseases (CIMUS) Campus Vida, University of Santiago de Compostela, Santiago de Compostela, Spain.
authors: Marcos
authors: M
authors: García-Fuentes
authors: Department of Pharmaceutics and Pharmaceutical Technology, School of Pharmacy, Campus Vida, University of Santiago de Compostela, Santiago de Compostela, Spain; Center for Research in Molecular Medicine and Chronic Diseases (CIMUS) Campus Vida, University of Santiago de Compostela, Santiago de Compostela, Spain.
authors: Maria José
authors: MJ
authors: Alonso
authors: Department of Pharmaceutics and Pharmaceutical Technology, School of Pharmacy, Campus Vida, University of Santiago de Compostela, Santiago de Compostela, Spain; Center for Research in Molecular Medicine and Chronic Diseases (CIMUS) Campus Vida, University of Santiago de Compostela, Santiago de Compostela, Spain. Electronic address: dolores.torres@usc.es.
authors: Dolores
authors: D
authors: Torres
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D003692:Delayed-Action Preparations; D000077143:Docetaxel; D000089662:Doublecortin Protein; D004337:Drug Carriers / Q000737:chemistry* / Q000493:pharmacokinetics; D004912:Erythrocytes / Q000187:drug effects / Q000473:pathology; D005260:Female; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D053208:Kaplan-Meier Estimate; D051379:Mice; D053769:Nanocapsules / Q000737:chemistry*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D011099:Polyglutamic Acid / Q000097:blood / Q000737:chemistry*; D017208:Rats, Wistar; D013499:Surface Properties; D043823:Taxoids / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; C000714847:Dcx protein, mouse; C000714848:Dcx protein, rat; D003692:Delayed-Action Preparations; D000089662:Doublecortin Protein; D004337:Drug Carriers; D053769:Nanocapsules; D043823:Taxoids; D000077143:Docetaxel; D011099:Polyglutamic Acid; D011092:Polyethylene Glycols
keywords: Anticancer drug delivery; Biocompatibility; Drug targeting; Nanotechnology; PEGylation; Polyaminoacids