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Poly(lactic acid) nanoparticles labeled with biologically active Neutravidin for active targeting

Nobs, Leila
Published in European journal of pharmaceutics and biopharmaceutics. 2004, vol. 58, no. 3, p. 483-90
Abstract In this study, NeutrAvidin was covalently bound to the surface of poly(DL-lactic acid) (PLA) nanoparticles, with the aim of attaching targeting compounds, such as proteins, to their surface. Sulfhydryl groups were first introduced on the surface of PLA nanoparticles through a carbodiimide reaction. NeutrAvidin was then bound to the thiolated nanoparticles via a bifunctional cross-linker, which offers two binding sites, one for primary amine groups and one for thiol functions. The amount of sulfhydryl groups obtained on the surface of the nanoparticles was determined. The NeutrAvidin -labeled nanoparticles were evaluated with respect to particle size, protein concentration and biotin binding capacity. The concentration of thiol functions on the surface of nanoparticles was 105 +/- 15 mmol/mol PLA. The quantification of NeutrAvidin coupled to the nanoparticles revealed that a significant amount of the protein was covalently bound to the nanoparticles. The concentration of NeutrAvidin bound to the nanoparticles could be controlled by varying the amount of protein during the coupling reaction. The maximum concentration of NeutrAvidin attached to the particles was 6 mmol per mol of PLA. The specific activity of NeutrAvidin bound to the nanoparticles was also evaluated and results revealed that the protein maintained the capacity to bind biotin. The activity of the NAR-labeled nanoparticles was lower than expected, due to the undesired aggregation of the native NeutrAvidin. Altogether, the results suggest that other proteins, such as antibodies could be coupled to the nanoparticles for active targeting. Furthermore, PLA nanoparticles bearing NeutrAvidin are interesting candidates for active targeting with biotinylated antibodies using the biotin-avidin interaction in a two step procedure.
Keywords NanoparticlesPoly(DL-lactic acid)Sulfhydryl functionsSurface chemistryNeutrAvidineDrug targeting
PMID: 15451522
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Research group Technologie pharmaceutique
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NOBS, Leila et al. Poly(lactic acid) nanoparticles labeled with biologically active Neutravidin for active targeting. In: European journal of pharmaceutics and biopharmaceutics, 2004, vol. 58, n° 3, p. 483-90. doi: 10.1016/j.ejpb.2004.04.006 https://archive-ouverte.unige.ch/unige:84829

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Deposited on : 2016-06-29

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