title: 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.
abstract: In this study the potential of 2 different ligands, i.e., palmitoyl mannose (Man-Lip) and 4-SO(4)GalNAc (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-SO(4)GalNAc 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-SO(4)GalNAc possesses a promising feature for targeting resident macrophages and its application in the conditions of leishmaniasis is in the offing.
  
  
  BACKGROUND
  This 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.
authors.affiliation: Pharmaceutics Division, CSIR-Central Drug Research Institute, Lucknow, India. mishrapr@hotmail.com
authors.forename: Deepak
authors.initials: D
authors.lastname: Singodia
authors.forename: Ashwni
authors.initials: A
authors.lastname: Verma
authors.forename: Rahul K
authors.initials: RK
authors.lastname: Verma
authors.forename: Prabhat Ranjan
authors.initials: PR
authors.lastname: Mishra
mesh_terms: D000117:Acetylglucosamine / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D000666:Amphotericin B / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D002460:Cell Line; D004353:Drug Evaluation, Preclinical; D006801:Humans; D037181:Lectins, C-Type / Q000819:agonists*; D007896:Leishmaniasis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008081:Liposomes; D008264:Macrophages / Q000378:metabolism*; D008358:Mannose / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000819:agonists*; D051379:Mice; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000819:agonists*
chemical_list: D000981:Antiprotozoal Agents; D037181:Lectins, C-Type; D008081:Liposomes; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D000666:Amphotericin B; D008358:Mannose; D000117:Acetylglucosamine