Investigations into an alternate approach to target mannose receptors on macrophages using 4-sulfated N-acetyl galactosamine more efficiently in comparison with mannose-decorated liposomes: an application in drug delivery

In this study the potential of 2 different ligands, i.e., palmitoyl mannose (Man-Lip) and 4-SO4GalNAc (Sulf-Lip) to target resident macrophages was investigated after surface decoration of Amphotericin B (AmB) loaded liposomes. In the case of Sulf-Lip, the 4-SO4GalNAc was adsorbed through electrostatic interaction on cationic liposomes, which was confirmed by change in zeta potential from +48.2 ± 3.7 mV for Lip to +12.2 ± 1.3 mV for Sulf-Lip. The mean particle size of Sulf-Lip and Man-Lip was found to be 139.4 ± 7.4 nm and 147.4 ± 8.6 nm, respectively. Flow cytometric data reveal enhanced uptake of Sulf-Lip in both J774 and RAW cell lines in comparison with the uptake of Man-Lip. Intracellular localization studies indicate that the fluorescence intensity of Sulf-Lip was much higher in comparison with that of Man-Lip and Lip formulations. Sulf-Lip and Man-Lip showed significantly higher localization of AmB at all time points in comparison with Lip (P < 0.05) after intravenous (IV) administration. The studies provide evidence that 4-SO4GalNAc possesses a promising feature for targeting resident macrophages and its application in the conditions of leishmaniasis is in the offing.From the Clinical EditorThis in vivo study compares two different ligands to deliver Amphotericin B l(AmB) loaded liposomes to resident macrophages. Targeted approaches showed significantly higher localization of AmB at all time points in comparison to non-targeted liposomes, and future applications in leishmaniasis are already under preparation.

Graphical AbstractSchematic diagram presents mannose moiety attach with C-type carbohydrate recognition domain (CRD), while 4-sulfated galactosamine targets cysteine rich domain on mannose receptor. 3 and 4- hydroxyl group on mannose form hydrogen bond with C-type CRD while sulfate moiety on 4-sulfated galactosamine form six hydrogen bond with cysteine rich domain.Figure optionsDownload high-quality image (97 K)Download as PowerPoint slide