title: Bioinspired Calcium Phosphate Nanoparticles Featuring as Efficient Carrier and Prompter for Macrophage Intervention in Experimental Leishmaniasis.
abstract: To develop a biocompatible and bioresorbable calcium phosphate (CaP) nanoparticles (NPs) bearing Amphotericin B (AmB) with an aim to provide macrophage specific targeting in visceral leishmaniasis (VL).
  
  
  
  CaP-AmB-NPs were architectured through emulsion precipitation method. The developed formulation was extensively characterized for various parameters including in-vitro and in-vivo antileishmanial activity. Moreover, plasma pharmacokinetics, tissue biodistribution and toxicity profile were also assessed.
  
  
  
  Optimized CaP-AmB-NPs exhibited higher entrapment (71.1 ± 6.68%) of AmB. No trend related to higher hemolysis was apparent in the developed formulation as evidenced in commercially available colloidal and liposomal formulations. Cellular uptake of the developed CaP-AmB-NPs was quantified through flow cytometry in J774A.1 cell line, and a 23.90 fold rise in uptake was observed. Fluorescent microscopy also confirmed the time dependent rise in uptake. In-vivo multiple dose toxicity study demonstrated no toxicity upto 5 mg/kg dose of AmB. Plasma kinetics and tissue distribution studies established significantly higher concentration of AmB in group treated with CaP-AmB-NPs in liver and spleen as compared to CAmB, LAmB and AmB suspension group. In-vivo animal experimental results revealed that the CaP-AmB-NPs showed higher splenic parasite inhibition compared to CAmB and LAmB in leishmania parasite infected hamsters.
  
  
  
  The investigated CaP-AmB-NPs are effective in provoking macrophage mediated uptake and collectively features lower toxicity and offers a suitable replacement for available AmB-formulations for the obliteration of intra-macrophage VL parasite.
authors.affiliation: Amity Institute of Pharmacy, Amity University, Lucknow, UP, 226 028, India. mohinichaurasia@gmail.com.
authors.forename: Mohini
authors.initials: M
authors.lastname: Chaurasia
authors.affiliation: Pharmaceutics Division, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Lucknow, India, 226031.
authors.forename: Pankaj K
authors.initials: PK
authors.lastname: Singh
authors.affiliation: Parasitology Division, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Lucknow, India, 226031.
authors.forename: Anil K
authors.initials: AK
authors.lastname: Jaiswal
authors.affiliation: Pharmaceutics Division, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Lucknow, India, 226031.
authors.forename: Animesh
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Pharmaceutics Division, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Lucknow, India, 226031.
authors.forename: Vivek K
authors.initials: VK
authors.lastname: Pawar
authors.affiliation: Parasitology Division, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Lucknow, India, 226031.
authors.forename: Anuradha
authors.initials: A
authors.lastname: Dube
authors.affiliation: Department of Pharmacy, Banasthali University, Banasthali, India, 304022.
authors.forename: Sarvesh K
authors.initials: SK
authors.lastname: Paliwal
authors.affiliation: Pharmaceutics Division, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Lucknow, India, 226031.
authors.forename: Manish K
authors.initials: MK
authors.lastname: Chourasia
mesh_terms: D000666:Amphotericin B / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D002130:Calcium Phosphates / Q000737:chemistry*; D002460:Cell Line; D006224:Cricetinae; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D004655:Emulsions; D004912:Erythrocytes / Q000187:drug effects; D006461:Hemolysis; D007893:Leishmania donovani / Q000187:drug effects; D007898:Leishmaniasis, Visceral / Q000188:drug therapy* / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D053758:Nanoparticles / Q000737:chemistry*; D017208:Rats, Wistar; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D000981:Antiprotozoal Agents; D002130:Calcium Phosphates; D004337:Drug Carriers; D004655:Emulsions; C068538:liposomal amphotericin B; D000666:Amphotericin B
keywords: amphotericin B; calcium phosphate; macrophage targeting; nanoparticles; visceral leishmaniasis