title: Self assembled ionically sodium alginate cross-linked amphotericin B encapsulated glycol chitosan stearate nanoparticles: applicability in better chemotherapy and non-toxic delivery in visceral leishmaniasis.
abstract: OBJECTIVE
  To investigate the applicability, localization, biodistribution and toxicity of self assembled ionically sodium alginate cross-linked AmB loaded glycol chitosan stearate nanoparticles for effective management of visceral leishmaniasis.
  
  
  METHODS
  Here, we fabricated Amphotericin B (AmB) encapsulated sodium alginate-glycol chitosan stearate nanoparticles (AmB-SA-GCS-NP) using strong electrostatic interaction between oppositely charged polymer and copolymer by ionotropic complexation method. The tagged FAmB-SA-GCS-NP was compared with tagged FAmB for in vitro macrophagic uptake in J774A macrophages and in vivo localization in liver, spleen, lung and kidney tissues. The AmB-SA-GCS-NP and plain AmB were compared for in vitro and in vivo antileishmanial activity, pharmacokinetics, organ distribution and toxicity profiling.
  
  
  RESULTS
  The morphology of SA-GCS-NP revealed as nanocrystal (size, 196.3 ± 17.2 nm; PDI, 0.216 ± 0.078; zeta potential, (-) 32.4 ± 5.1 mV) by field emission scanning electron microscopy and high resolution transmission electron microscopy. The macrophage uptake and in vivo tissue localization studies shows tagged FAmB-SA-GCS-NP has significantly higher (~1.7) uptake compared to tagged FAmB. The biodistribution study of AmB-SA-GCS-NP showed more localized distribution towards Leishmania infected organs i.e. spleen and liver while lesser towards kidney. The in vitro (IC50, 0.128 ± 0.024 μg AmB/ml) and in vivo (parasite inhibition, 70.21 ± 3.46%) results of AmB-SA-GCS-NP illustrated significantly higher (P < 0.05) efficacy over plain AmB. The monomeric form of AmB within SA-GCS-NP, observed by UV-visible spectroscopy, favored very less in vitro and in vivo toxicities compared to plain AmB.
  
  
  CONCLUSIONS
  The molecular organization, toxicity studies, desired localization and biodistribution of cost effective AmB-SA-GCS-NP was found to be highly effective and can be proved as practical delivery platform for better management of leishmaniasis.
authors.affiliation: Pharmaceutics Division, Preclinical South PCS 002/011, CSIR-Central Drug Research Institute B.S. 10/1, Sector-10, Jankipuram Extension, Sitapur Road, Lucknow, 226031, India, pramodcdri10@gmail.com.
authors.forename: Pramod K
authors.initials: PK
authors.lastname: Gupta
authors.forename: Anil K
authors.initials: AK
authors.lastname: Jaiswal
authors.forename: Shalini
authors.initials: S
authors.lastname: Asthana
authors.forename: Ashwni
authors.initials: A
authors.lastname: Verma
authors.forename: Vivek
authors.initials: V
authors.lastname: Kumar
authors.forename: Prashant
authors.initials: P
authors.lastname: Shukla
authors.forename: Pankaj
authors.initials: P
authors.lastname: Dwivedi
authors.forename: Anuradha
authors.initials: A
authors.lastname: Dube
authors.forename: Prabhat R
authors.initials: PR
authors.lastname: Mishra
mesh_terms: D000464:Alginates / Q000737:chemistry*; D000666:Amphotericin B / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D002460:Cell Line; D048271:Chitosan / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D007893:Leishmania donovani / Q000187:drug effects*; D007898:Leishmaniasis, Visceral / Q000188:drug therapy*; D008264:Macrophages / Q000469:parasitology; D008297:Male; D008647:Mesocricetus; D053758:Nanoparticles / Q000737:chemistry; D017208:Rats, Wistar; D013228:Stearates / Q000737:chemistry
chemical_list: D000464:Alginates; D000981:Antiprotozoal Agents; D004337:Drug Carriers; D006603:Hexuronic Acids; D013228:Stearates; C118638:glycol-chitosan; D000666:Amphotericin B; D020723:Glucuronic Acid; D048271:Chitosan