Journal
INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume 363, Issue 1-2, Pages 170-176Publisher
ELSEVIER
DOI: 10.1016/j.ijpharm.2008.07.006
Keywords
Doxorubicin; Nanoparticles; Controlled release/delivery; Magnetic drug targeting; Cancer cell
Categories
Funding
- Ligue Nationale contre le Cancer
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A new method of reversible association of doxorubicin (DOX) to superparamagnetic iron oxide nanoparticles (SPION) is developed for magnetically targeted chemotherapy. The efficacy of this approach is evaluated in terms of drug loading, delivery kinetics and cytotoxicity in vitro. Aqueous suspensions of SPION (ferrofluids) were prepared by coprecipitation of ferric and ferrous chlorides in alkaline medium followed by Surface oxidation by ferric nitrate and surface treatment with citrate ions. The ferrofluids were loaded with DOX using a pre-formed DOX-Fe2+ complex. The resulting drug loading was as high as 14% (w/w). This value exceeds the maximal loading known from literature up today. The release of DOX from the nanoparticles is strongly pH-dependent: at pH 7.4 the amount of drug released attains a plateau of similar to 85% after 1 h, whereas at pH 4.0 the release is almost immediate. At both pH, the released drug is iron-free. The in vitro cytotoxicity of the DOX-loaded SPION on the MCF-7 breast cancer cell line is similar to that of DOX in solution or even higher, at low-drug concentrations. The present study demonstrates the potential of the novel method of pH-sensitive DOX-SPION association to design novel magnetic nanovectors for chemotherapy. (c) 2008 Elsevier B.V. All rights reserved.
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