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  • Title: Nanoparticulate drug carriers based on hybrid poly(D,L-lactide-co-glycolide)-dendron structures.
    Author: Costantino L, Gandolfi F, Bossy-Nobs L, Tosi G, Gurny R, Rivasi F, Vandelli MA, Forni F.
    Journal: Biomaterials; 2006 Sep; 27(26):4635-45. PubMed ID: 16716395.
    Abstract:
    We describe a general method for incorporating target moieties in a well-defined arrangement into the surface of biocompatible polyester poly(D,L-lactic-co-glycolic acid) (PLGA) materials using dendrons. In this way it is possible to obtain nanoparticles (NPs) with a high degree of surface coverage. This new strategy was successfully applied to the preparation of peptide- and beta-D-glucose-covered NPs. The first application is based on the discovery of NPs made of conjugates between PLGA and short peptidic sequences able to cross the blood-brain barrier (BBB) after systemic administration. In this paper, we used a branched structure (dendron) in order to prepare a derivative of PLGA able to form, by simple nanoprecipitation, NPs with a higher degree of surface coverage than previously reported by us, characteristic that could influence the uptake by the liver and spleen. The NPs thus obtained retain the ability to cross the BBB and possess a core-shell structure, as evidenced from zeta-potential, X-ray photoelectron (ESCA) spectroscopy and elemental analyses. These results are comparable with the NPs obtained by the derivatization of preformed NPs. The same strategy, namely the use of a branched spacer (a dendron or a G1 dendrimer) inserted between one end of the PLGA chain and a derivatizing molecule, was also successfully applied to obtain beta-D-glucose-covered NPs; in this case, the surface analysis of the NPs was performed by using high resolution magic angle spinning (HRMAS) NMR spectroscopy and zeta-potential measurements.
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