International Journal of Pharmaceutics 2014-10-01

Target selective micelles for bombesin receptors incorporating Au(III)-dithiocarbamato complexes.

Paola Ringhieri, Roberta Iannitti, Chiara Nardon, Rosanna Palumbo, Dolores Fregona, Giancarlo Morelli, Antonella Accardo

Index: Int. J. Pharm. 473(1-2) , 194-202, (2014)

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Abstract

Pure sterically stabilized micelles (SSM) of DSPE-PEG2000, and sterically stabilized mixed micelles (SSMM) containing PC or DOPC phospholipids (5, 10 or 20% mol/mol with respect to DSPE-PEG2000) are developed as delivery systems for the gold based cytotoxic drug Au(III)-dithiocarbamato complex AuL12. In particular, SSMM containing 5% of PC at 5mM of lipid concentration encapsulates 61.0 μg of AuL12 with a DL% of 1.13. The gold complex remains stable up to 72 h when incorporated in the aggregate, as indicated by UV-vis measurements. Incorporation in micelle composition of a low amount of the peptide derivative MonY-BN-AA1, containing a bombesin peptide analogue does not influence structural parameters of the micelles (diameter around 20 nm) neither the AuL12 loading parameters. Target selective properties of the peptide containing full aggregate on PC-3 cells overexpressing the GRP/bombesin receptors are observed by in vitro cytotoxic studies: a decrease of cell viability, ∼ 50%, is obtained in cells treated with AuL12-targeted micelles at 10 μM drug concentration for 48 h with respect to untargeted micelles.Copyright © 2014 Elsevier B.V. All rights reserved.