Self-assembling chitosan/poly-γ-glutamic acid nanoparticles for targeted drug delivery

• Published in: Colloid and polymer science Vol. 287; no. 7; pp. 759 - 765
• Main Authors: Keresztessy, Zsolt, Bodnár, Magdolna, Ber, Elizabeth, Hajdu, István, Zhang, Min, Hartmann, John F, Minko, Tamara, Borbély, János
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Berlin/Heidelberg : Springer-Verlag 2009; Springer-Verlag; Springer
• Subjects: Aminoacid polymers; Applied sciences; Biological and medical sciences; Characterization and Evaluation of Materials; Chemistry; Chemistry and Materials Science; Complex Fluids and Microfluidics; Exact sciences and technology; Food Science; General pharmacology; Medical sciences; Nanotechnology and Microengineering; Natural polymers; Original Contribution; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Physical Chemistry; Physicochemistry of polymers; Polymer Sciences; Soft and Granular Matter; Starch and polysaccharides; Synthetic biopolymers; Nanoparticles; toxicity; Cellular uptake; Cytotoxicity; Chitosan; PGA; Poly-γ-glutamic acid; Biological properties; Antineoplastic agent; Targeting; Nanoparticle; In vivo tonicity; Drug carrier; Folic acid; Interpolymer; Manufacturing; Tumor cell; Growth from solution; Control release polymer; Gelation; Experimental study; In vitro; Aminoacid polymer; Poly-y-glutamic acid; Polyelectrolyte; Particle size distribution; Internalization; Oside polymer; Glutamic acid polymer
• ISSN: 0303-402X; 1435-1536
• DOI: 10.1007/s00396-009-2022-3

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.