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Surface Engineered Carboxymethylchitosan/Poly(amidoamine) Dendrimer Nanoparticles for Intracellular Targeting
Authors:Joaquim M Oliveira  Noriko Kotobuki  Alexandra P Marques  Rogério P Pirraco  Johan Benesch  Motohiro Hirose  Silgia A Costa  João F Mano  Hajime Ohgushi  Rui L Reis
Affiliation:1. 3B's Research Group—Biomaterials, Biodegradables and Biomimetics IBB—Institute for Biotechnology and Bioengineering PT Government Associated Laboratory Department of Polymer Engineering University of Minho, Campus Gualtar, 4710‐057 Braga (Portugal);2. Research Institute for Cell Engineering (RICE) National Institute of Advanced Industrial Science and Technology (AIST) Nakoji 3‐11‐46, Amagasaki, Hyogo 661‐0974 (Japan)
Abstract:Novel highly branched biodegradable macromolecular systems have been developed by grafting carboxymethylchitosan (CMCht) onto low generation poly(amidoamine) (PAMAM) dendrimers. Such structures organize into sphere‐like nanoparticles that are proposed to be used as carriers to deliver bioactive molecules aimed at controlling the behavior of stem cells, namely their proliferation and differentiation. The nanoparticles did not exhibit significant cytotoxicity in the range of concentrations below 1 mg mL?1, and fluorescent probe labeled nanoparticles were found to be internalized with highly efficiency by both human osteoblast‐like cells and rat bone marrow stromal cells, under fluorescence‐activated cell sorting and fluorescence microscopy analyses. Dexamethasone (Dex) has been incorporated into CMCht/PAMAM dendrimer nanoparticles and release rates were determined by high performance liquid chromatography. Moreover, the biochemical data demonstrates that the Dex‐loaded CMCht/PAMAM dendrimer nanoparticles promote the osteogenic differentiation of rat bone marrow stromal cells, in vitro. The nanoparticles exhibit interesting physicochemical and biological properties and have great potential to be used in fundamental cell biology studies as well as in a variety of biomedical applications, including tissue engineering and regenerative medicine.
Keywords:dendrimers  drug delivery  nanoparticles
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