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Anti-tumor efficacy of chitosan-g-poly(ethylene glycol) nanocapsules containing docetaxel: anti-TMEFF-2 functionalized nanocapsules vs. non-functionalized nanocapsules.

Abstract
The development and evaluation of PEGylated chitosan (CS) nanocapsules (NCs) conjugated to a monoclonal antibody anti-TMEFF-2 (CS-PEG-anti-TMEFF-2 mAb NCs) for targeted delivery of docetaxel (DCX) is presented. CS-PEG-Biotin NCs, displaying biotin tags at their surface, were obtained and efficiently functionalized with an anti-TMEFF-2 mAb through a convenient avidin-biotin approach. Cell cycle analysis after treatment with different DCX-loaded CS-PEG NC formulations indicated that the encapsulated drug remained fully active, showing a similar functional behavior to free DCX. In vivo efficacy studies using a non-small cell lung carcinoma xenograft revealed that CS-PEG-anti-TMEFF-2 NCs resulted as effective as free DCX (Taxotere®). Interestingly, differences on the pharmacodynamic behavior among the different DCX formulations were observed. Thus, while free DCX exhibited a fast and short effect on tumor volume reduction, CS-PEG-anti-TMEFF-2 mAb NCs showed a delayed and prolonged action, with no significant side effects of treatments.
AuthorsDaniel Torrecilla, Maria V Lozano, Enrique Lallana, Jose I Neissa, Ramon Novoa-Carballal, Anxo Vidal, Eduardo Fernandez-Megia, Dolores Torres, Ricardo Riguera, Maria J Alonso, Fernando Dominguez
JournalEuropean journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V (Eur J Pharm Biopharm) Vol. 83 Issue 3 Pg. 330-7 (Apr 2013) ISSN: 1873-3441 [Electronic] Netherlands
PMID23262164 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2012 Elsevier B.V. All rights reserved.
Chemical References
  • Antineoplastic Agents
  • Dcx protein, mouse
  • Doublecortin Protein
  • Membrane Proteins
  • Nanocapsules
  • Neoplasm Proteins
  • TMEFF2 protein, human
  • Taxoids
  • Docetaxel
  • Polyethylene Glycols
  • Chitosan
Topics
  • Animals
  • Antineoplastic Agents (chemistry, pharmacology)
  • Cell Line, Tumor
  • Chitosan (chemistry)
  • Docetaxel
  • Doublecortin Protein
  • Humans
  • Magnetic Resonance Spectroscopy
  • Membrane Proteins (antagonists & inhibitors)
  • Mice
  • Mice, SCID
  • Nanocapsules
  • Neoplasm Proteins (antagonists & inhibitors)
  • Polyethylene Glycols (chemistry)
  • Taxoids (chemistry, pharmacology)
  • Xenograft Model Antitumor Assays

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