Glycopeptide-decorated nanoparticles as drug carriers for CNS: effects of surface coverage and carbohydrate type

n order to study the ability of peptide-decorated PLGA Np to act as CNS drug delivery agents, the effect of various degrees of Np surface coverage by the peptide H2N-Gly-L-Phe-D-Thr-Gly-L-Phe-L-Leu-L-Ser(O-R)-CONH2 (R = -D-glucose) and of the type of carbohydrate present on Ser (R= H, -D-glucose, -D-xylose, -D-lactose, -D-Mannose) were evaluated. Loperamide was used as a model drug and its presence on rat CNS was evaluated by means of its pharmacological effect (antinociceptive assay, hot-plate test). The pharmacological effect exerted by loperamide loaded into Np demonstrated to be strongly dependent on the degree of peptidic surface coverage of Np. Thus, in the presence of a high surface coverage, a very short effect is observed, which appears early on (0.5 min) after Np iv administration. Moreover, the sugar moiety influences markedly the CNS effect of loperamide loaded into the peptide-decorated Np: among the carbohydrates here examined, the presence of Beta-D-glucose on the Ser of the peptide showed the best results, both in terms of the maximum effect and length.