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A pharmaceutical study of doxorubicin-loaded PEGylated nanoparticles for magnetic drug targeting.

International journal of pharmaceutics (2011-06-28)
J Gautier, E Munnier, A Paillard, K Hervé, L Douziech-Eyrolles, M Soucé, P Dubois, I Chourpa
ABSTRACT

One of the new strategies to improve cancer chemotherapy is based on new drug delivery systems, like the polyethylene glycol-coated superparamagnetic iron oxide nanoparticles (PEG-SPION, thereafter called PS). In this study, PS are loaded with doxorubicin (DOX) anticancer drug, using a pre-formed DOX-Fe(2+) complex reversible at lower pH of tumour tissues and cancer cells. The DOX loaded PS (DLPS, 3% w/w DOX/iron oxide) present a hydrodynamic size around 60nm and a zeta potential near zero at physiological pH, both parameters being favourable for increased colloidal stability in biological media and decreased elimination by the immune system. At physiological pH of 7.4, 60% of the loaded drug is gradually released from the DLPS in ∼2h. The intracellular release and distribution of DOX is followed by means of confocal spectral imaging (CSI) of the drug fluorescence. The in vitro cytotoxicity of the DLPS on MCF-7 breast cancer cells is equivalent to that of a DOX solution. The reversible association of DOX to the SPION surface and the role of polymer coating on the drug loading/release are discussed, both being critical for the design of novel stealth magnetic nanovectors for chemotherapy.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
(3-Aminopropyl)trimethoxysilane, 97%
Sigma-Aldrich
Iron(III) nitrate nonahydrate, ≥99.95% trace metals basis
Sigma-Aldrich
Iron(III) nitrate nonahydrate, ≥99.999% trace metals basis
Sigma-Aldrich
Iron(III) nitrate nonahydrate, BioReagent, suitable for cell culture
Supelco
Iron standard for AAS, analytical standard, 10.00 g/L Fe in nitric acid, traceable to BAM
Sigma-Aldrich
Iron(III) nitrate nonahydrate, ACS reagent, ≥98%