title: Development of nanocapsules bearing doxorubicin for macrophage targeting through the phosphatidylserine ligand: a system for intervention in visceral leishmaniasis.
abstract: OBJECTIVE
  The purpose of this study was to explore the applicability, targeting potential and drug delivery to specialized phagocytes via phosphatidylserine (PS)-specific ligand-anchored nanocapsules (NCs) bearing doxorubicin.
  
  
  METHODS
  The layer-by-layer method was utilized to prepare NCs having a nanoemulsion core loaded with doxorubicin (NCs-DOX), which was further grafted with PS. PS-coated NCs (PS-NCs-DOX) were compared with NCs-DOX for in vitro targeting ability by studying uptake by macrophages, intracellular localization, in vivo pharmacokinetics and organ distribution studies. The in vivo antileishmanial activity of free doxorubicin, NCs-DOX and PS-NCs-DOX was tested against visceral leishmaniasis in Leishmania donovani-infected hamsters.
  
  
  RESULTS
  Flow cytometric data revealed 1.75-fold enhanced uptake of PS-NCs-DOX in J774A.1 macrophage cell lines compared with NCs-DOX. In vivo organ distribution studies in Wistar rats demonstrated a significantly higher extent of accumulation of PS-NCs-DOX compared with NCs-DOX in macrophage-rich organs, particularly in liver and spleen. Highly significant antileishmanial activity (P < 0.05 compared with NCs) was observed with PS-NCs-DOX, causing 85.23% ± 4.49% inhibition of splenic parasitic burden. NCs-DOX and free doxorubicin caused only 72.88% ± 3.87% and 42.85% ± 2.11% parasite inhibition, respectively, in Leishmania-infected hamsters (P < 0.01 for PS-NCs-DOX versus free doxorubicin and NCs-DOX versus free doxorubicin).
  
  
  CONCLUSIONS
  We conclude that the PS targeting moiety can provide a new insight for efficient drug delivery to specialized macrophages and thus may be developed for effective use in macrophage-specific delivery systems, especially for leishmaniasis.
authors.affiliation: Pharmaceutics Division,  CSIR-Central Drug Research Institute, Chattar Manzil Palace, Lucknow 226001,  India.
authors.forename: Shaswat
authors.initials: S
authors.lastname: Kansal
authors.forename: Rati
authors.initials: R
authors.lastname: Tandon
authors.forename: Pankaj
authors.initials: P
authors.lastname: Dwivedi
authors.forename: Pragya
authors.initials: P
authors.lastname: Misra
authors.forename: P R P
authors.initials: PR
authors.lastname: Verma
authors.forename: Anuradha
authors.initials: A
authors.lastname: Dube
authors.forename: Prabhat Ranjan
authors.initials: PR
authors.lastname: Mishra
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006224:Cricetinae; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000008:administration & dosage* / Q000493:pharmacokinetics; D007893:Leishmania donovani / Q000187:drug effects; D007898:Leishmaniasis, Visceral / Q000188:drug therapy*; D008264:Macrophages / Q000469:parasitology*; D008297:Male; D008647:Mesocricetus; D053769:Nanocapsules / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome
chemical_list: D000981:Antiprotozoal Agents; D004337:Drug Carriers; D053769:Nanocapsules; D004317:Doxorubicin