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Over the last decade, polymer micelles and nanoparticles attracted an increasing interest in drug research because they can be used as efficient drug delivery systems 1 . Nanoparticles are submicron-sized polymeric colloidal particles with a therapeutic agent of interest encapsulated within their polymeric matrix 2 . The addition of an amphiphilic block copolymer made up of poly(ethylene oxide) and an aliphatic polyester, such as poly(ε-caprolactone) (PCL) or polylactide (PLA), to the formulation permits to take advantage of the protein repellent properties of PEO to increase the time live of the nanoparticles in the vascular residence.The use of polymeric nanoparticles for the delivery of complex antigens, the combination of antigens, and genetic vaccines makes them one of the most promising strategies for oral vaccination 3 . Polymeric carriers protect antigens against degradation and inactivation in the harsh gastro-intestinal environment and have the ability to enhance their transmucosal transport. When these copolymers have a targeting agent, the biodistribution of polymeric micelles can be modulated and can induce specific cellular uptake by receptor-mediated endocytosis.

We report the synthesis of fully biodegradable polymeric nanoparticles presenting mannose residues at their surface and their interaction with lectins. A simple and versatile method was used to reach the surface functionalization of poly(D,L-lactic acid) (PLA) nanoparticles by mannose moieties: It consists in using an amphiphilic mannosylated poly(ethylene oxide)-b-poly(E-caprolactone) (PEO-b-PCL) diblock copolymer as a bioresorbable surface modifier in a simple nanoprecipitation-evaporation procedure. The size and zeta potential of the nanoparticles were found to depend on the molar copolymer/PLA ratio, demonstrating the influence of the copolymer on the formation of the nanoparticles. The bioavailability of the mannose residues as specific recognition sites on the nanoparticle surface could be demonstrated by a modified enzyme-linked lectin assay (ELLA) using biotin-labeled lectins which interact specifically with alpha-D-mannopyrannoside derivatives. Besides specific interaction by lectin-mannose complex formation, nonspecific adsorption of the proteins on the nanoparticle surface was observed. These results were fully supported by isothermal titration calorimetry experiments which suggested that the balance between specific and nonspecific interactions can be controlled by the amount of glycosylated polymer used for the preparation of the nanoparticles. Such nanoparticles are expected to be specifically recognized by mannose receptors, which are highly expressed in cells of the immune system. The targeting properties of these carrier systems combined with their potential adjuvant effects due to their size in the range of 200-300 nm make them attractive candidates as vaccine delivery systems.

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