title: Development of targeted 1,2-diacyl-sn-glycero-3-phospho-l-serine-coated gelatin nanoparticles loaded with amphotericin B for improved in vitro and in vivo effect in leishmaniasis.
abstract: OBJECTIVE
  The principle objective of this study was to develop 1,2-diacyl-sn-glycero-3-phospho-l-serine (PS)-coated gelatin nanoparticles (GNPs) bearing amphotericin B (AmB) for specific targeting to the macrophages involved in visceral leishmaniasis (VL).
  
  
  METHODS
  The two-step desolvation method has been used for the preparation of GNPs with AmB, which was further coated with PS (PS-AmB-GNPs). The targeting potential of it was compared with uncoated AmB-loaded GNPs (AmB-GNPs) for in vitro and in vivo macrophage uptake.
  
  
  RESULTS
  The results of flow cytometric data revealed enhanced uptake of PS-AmB-GNPs in J774A.1 macrophage cell lines compared with AmB-GNPs. In vivo organ distribution studies in Wistar rats demonstrated a significantly higher extent of accumulation of PS-AmB-GNPs compared with AmB-GNPs in macrophage-rich organs, particularly in liver and spleen. The in vivo anti-leishmanial activity of plain AmB, AmB-GNPs and PS-AmB-GNPs was tested against VL in Leishmania donovani-infected hamsters. Highly significant anti-leishmanial activity (p < 0.05 compared with AmB-GNPs) was observed with PS-AmB-GNPs, causing 85.3 ± 7.89% inhibition of splenic parasitic burden. AmB-GNPs and plain AmB caused only 71.0 ± 3.87 and 50.5 ± 5.12% parasite inhibitions, respectively, in Leishmania-infected hamsters (p < 0.05 for PS-AmB-GNPs versus plain AmB and AmB-GNPs versus plain AmB).
  
  
  CONCLUSIONS
  The objective of the preparation was achieved and high accumulation of AmB in liver and spleen has been found, which resulted in enhanced anti-leishmanial activity.
authors.affiliation: CSIR-Central Drug Research Institute, Pharmaceutics Division , Lucknow-226031 , India.
authors.forename: Renuka
authors.initials: R
authors.lastname: Khatik
authors.forename: Pankaj
authors.initials: P
authors.lastname: Dwivedi
authors.forename: Prashant
authors.initials: P
authors.lastname: Khare
authors.forename: Shaswat
authors.initials: S
authors.lastname: Kansal
authors.forename: Anuradha
authors.initials: A
authors.lastname: Dube
authors.forename: Prabhat Ranjan
authors.initials: PR
authors.lastname: Mishra
authors.forename: Anil Kumar
authors.initials: AK
authors.lastname: Dwivedi
mesh_terms: D000666:Amphotericin B / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D002460:Cell Line; D002626:Chemistry, Pharmaceutical; D020099:Coated Materials, Biocompatible; D006224:Cricetinae; D004337:Drug Carriers; D005434:Flow Cytometry; D005780:Gelatin / Q000737:chemistry*; D007893:Leishmania donovani / Q000187:drug effects; D007898:Leishmaniasis, Visceral / Q000188:drug therapy*; D008099:Liver / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism / Q000469:parasitology; D008297:Male; D008647:Mesocricetus; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000737:chemistry; D009569:Nitric Oxide / Q000378:metabolism; D010316:Particle Size; D010718:Phosphatidylserines / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000378:metabolism
chemical_list: D000981:Antiprotozoal Agents; D020099:Coated Materials, Biocompatible; D004337:Drug Carriers; D010718:Phosphatidylserines; D009569:Nitric Oxide; C042511:1,2-dioleoylphosphatidylserine; D000666:Amphotericin B; D005780:Gelatin