Novel micelles based on amphiphilic branched PEG as carriers for fenretinide

• Published in: Nanomedicine 2012-08, Vol.8 (6), p.880-890
• Main Authors: Orienti, Isabella, PhD, Zuccari, Guendalina, PhD, Falconi, Mirella, MD, PhD, Teti, Gabriella, PhD, Illingworth, Nicola A., PhD, Veal, Gareth J., PhD
• Format: Article
• Language: English
• Subjects: Amphiphilic macromolecules; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - chemistry; Branched polyethylene glycol; Cell Line, Tumor; Cell Survival - drug effects; Crystallization - methods; Drug delivery; Drug Design; Fenretinide; Fenretinide - administration & dosage; Fenretinide - chemistry; Humans; Internal Medicine; Micellar complexes; Micelles; Nanocapsules - chemistry; Neuroblastoma - drug therapy; Neuroblastoma - pathology; Neuroblastoma - physiopathology; Polyethylene Glycols - chemistry
• ISSN: 1549-9634; 1549-9642
• DOI: 10.1016/j.nano.2011.10.008

Abstract This study reports on the preparation and evaluation of amphiphilic macromolecules based on branched polyethylene glycol covalently linked with alkyl hydrocarbon chains. These macromolecules easily dissolved in an aqueous environment, with formation of micellar nanoaggregates endowed with hydrophobic inner cores capable of hosting fenretinide by complexation. The complexes increased fenretinide aqueous solubility, while hindering its release as a free drug in an aqueous environment. Particle size analysis indicated dimensional suitability of the complexes for intravenous administration. Neuroblastoma cell lines (SH-SY5Y and NGP) exhibited increased sensitivity to fenretinide in complex as compared to free drug, associated with higher intracellular concentrations of fenretinide observed after treatment with the complex. Transmission electronic microscopy images revealed endocytosis of the micellar complex. Moreover, fenretinide conversion to its metabolite 4-oxo-fenretinide was delayed in cells treated with the complex, further supporting the hypothesis that fenretinide may be absorbed by micellar transport and exposed to the cytoplasm for conversion to its metabolite only after micelle destabilization. From the Clinical Editor Glioblastoma remains one of the most notoriously treatment-unresponsive brain cancer, and is clearly the most common such primary malignancy. This team of authors describe novel micelles based on amphiphilic branched PEG as carriers for fenretinide, and demonstrate their enhanced anti-tumor cell efficacy in cell cultures.