Doxorubicin loading, release, and stability of polyamidoamine dendrimer-coated magnetic nanoparticles

Abstract

Nanotechnology is a promising alternative to overcome the limitations of classical chemotherapy. As a novel approach, dendrimer-coated magnetic nanoparticles (DcMNPs) maintain suitable drug delivery system because of their buildup of functional groups, symmetry perfection, nanosize, and internal cavities. They can also be targeted to the tumor site in a magnetic field. The aim of this study is to obtain an effective targeted delivery system for doxorubicin, using polyamidoamine (PAMAM) DcMNPs. Different generations (G2, G3, G4, and G7) of PAMAM DcMNPs were synthesized. Doxorubicin loading, release, and stability efficiencies in these nanoparticles (NPs) were studied. The results showed that low-generation NPs obtained in this study have pH-sensitive drug release characteristics. G4DcMNP, which releases most of the drug in lower pH, seems to be the most suitable generation for efficient Doxorubicin delivery. Furthermore, application of doxorubicin-loaded G4DcMNPs may help to overcome doxorubicin resistance in MCF-7 cells. On the contrary, G2 and G3DcMNPs would be suitable for the delivery of drugs such as vinca alkaloids (Johnson IS, Armstrong JG, Gorman M, Burnett JP. 1963. Cancer Res 23:13901427.) and taxenes (Clarke SJ, Rivory LP. 1999. Clin Pharmacokinet 36(2):99114.), which show their effects in cytoplasm. The results of this study can provide new insights in the development of pH-sensitive targeted drug delivery systems to overcome drug resistance during cancer therapy. (c) 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:18251835, 2013