Covalent Binding of Mannosyl Ligand via 6-O Position and Glycolic Arm to Target a PLCA-Type Degradable Drug Carrier toward Macrophages

Abstract

Mononuclear phagocytes play a central role in the defense against important pathologies. Attempts were made to target drugs toward this cell type by using specific interactions between a mannose ligand and the lectin-type specific receptor present on the macrophage membrane. Basically, the use of a mannosyl radical as a homing device raised several problems: necessity to keep unmodified the part of the molecule which gives rise to lectin recognition, complex protection-deprotection chemistry, and blockage of the aldehyde function to preclude any side reaction. A new method was used to bind α-D-methylmannopy-ranoside, a commercially available precursor, through its primary hydroxyl group to the hydrosoluble bioresorbable drug carrier poly(L-lysine citramide imide). The method consisted of a few steps that did not require special protection of secondary hydroxyl groups. In the resulting conjugate, the pyranose structure of the sugar was retained. In vivo recognition of the conjugate by the lectin of mononuclear phagocytes was preserved.