Self-assembling chitosan/poly-γ-glutamic acid nanoparticles for targeted drug delivery
- 831 Downloads
For the purpose of targeted drug delivery, composite biodegradable nanoparticles were prepared from chitosan and the poly-γ-glutamic acid via an ionotropic gelation process. These stable self-assembled nanoparticles were characterized by dynamic light scattering, transmission electron microscopy, and atomic force microscopy, which demonstrated that the nanosystem consists of spherical particles with a smooth surface both in aqueous environment and in dried state. Toxicity measurements showed that the composition is nontoxic when tested either on cell cultures or in animal feeding experiments. To evaluate the potential of the nanosystem for intracellular drug delivery, the nanoparticles were fluorescently labeled and folic acid was attached as a cancer cell-specific targeting moiety. The ability of the particles to be internalized was tested using confocal microscopic imaging on cultured A2780/AD ovarian cancer cells, which overexpress folate receptors. The quantitative data obtained by digital processing of the intensity of green color of each pixel in the pictures inside the cell boundaries and total intensity of fluorescence inside the cells showed that “targeted” particles internalized into the cells significantly faster and the total accumulation of these particles was substantially higher in the cancer cells when compared with “nontargeted” particles, which may facilitate effective and specific cytoplasmic delivery of anticancer agents loaded into such nanoparticles.
KeywordsChitosan Poly-γ-glutamic acid PGA Nanoparticles Cytotoxicity In vivo toxicity Cellular uptake
This research was supported by the grant of Regional University Knowledge Center of Debrecen (Genomnanotech Debrecen, contract number RET-06/432/2004) and a grant from the New Jersey Commission on Science and Technology.
- 2.Majoros IJ, Thomas T, Baker JR Jr (2006) Molecular engineering in nanotechnology: engineered drug delivery. In: Reith M, Schommers W (eds) Handbook of theoretical and computational nanotechnology, vol 6. American Scientific, Stevenson Ranch, CA, pp 673–717Google Scholar
- 10.Khan MK, Nigavekar SS, Minc LD, Kariapper MST, Nair BM, Lesniak WG, Balogh LP (2005) In vivo biodistribution of dendrimers and dendrimer nanocomposites—implications for cancer imaging and therapy. Technol Cancer Res Threat 4:603–613Google Scholar