(Oligo)mannose functionalized hydroxyethyl starch nanocapsules: en route to drug delivery systems with targeting properties.

Hydroxyethyl starch nanocapsules (NCs) are potentially interesting hydrophilic drug delivery carriers, since they do not show non-specific interactions with the living cells. Only the presence of a targeting agent on their surface allows them to target specifically the desired site of action. In this paper, we report the synthesis and cell uptake of crosslinked hydroxyethyl starch (HES) NCs decorated with (oligo)mannose, which is an effective targeting agent for macrophage and dendritic cells. The crosslinked HES NCs were prepared via the interfacial polyaddition of HES with 2,4-toluene diisocyanate (TDI) in inverse (water-in-oil) miniemulsion and then functionalized with (oligo)mannose following two different strategies. To compare the activity and availability of a targeting agent, different types of mannose molecules such as α-d-mannopyranosylphenyl isothiocyanate, 3-O-(α-d-mannopyranosyl)-d-mannose and α3,α6-mannotriose were used for the functionalization of NCs. The availability of the mannose was unambiguously assessed by interaction with a fluorescent lectin. Moreover, the accessibility of the pilot molecule was improved by the presence of a PEG linker at the surface of the NCs. To simulate in vivo conditions, where proteins interact with nanoparticles with a possible hindrance of the accessibility to the targeting agent, the mannosylated NCs were first incubated with human serum before interaction with the fluorescent lectin. Enhancement of uptake into dendritic cells demonstrates the targeting ability in in vitro studies.