Synthesis, characterization of chitosan-tripolyphosphate conjugated chloroquine nanoparticle and its in vivo anti-malarial efficacy against rodent parasite: a dose and duration dependent approach

Int J Pharm. 2012 Sep 15;434(1-2):292-305. doi: 10.1016/j.ijpharm.2012.05.064. Epub 2012 Jun 1.

Abstract

Various strategies to deliver antimalarials using nanocarriers have been evaluated. However, taking into account the peculiarities of malaria parasites, the focus is placed mainly polymer-based chitosan nanocarriers. Our purpose of the study is to develop chitosan-tripolyphosphate (CS-TPP) nanoparticles (NPs) conjugated chloroquine in application for attenuation of Plasmodium berghei infection in Swiss mice. NPs were prepared by ionotropic gelation between CS and sodium TPP. In the study, the interaction of CS and TPP and the presence of chloroquine at the surface of chitosan-TPP NPs have been investigated by means of different methods like FTIR, DLS, and zeta potential. After drug preparation, effective dose of the nanoconjugated chloroquine (Nch) among 100, 250, and 500 mg/kg bw/day, was studied against P. berghei infection in Swiss mice by blood smear staining and biochemical assay of different inflammatory markers, and antioxidant enzyme levels also performed. After evaluating the effective dose, dose-dependent duration study was performed for 5, 10, 15 days. From the present study the maximum effect of Nch was found at 250 mg/kg bw concentration for 15 days treatment. So, this Nch might have potential of application as therapeutic anti-malarial and antioxidant agent.

MeSH terms

  • Animals
  • Antimalarials / administration & dosage
  • Antimalarials / pharmacology*
  • Chitosan / chemistry
  • Chloroquine / administration & dosage
  • Chloroquine / pharmacology*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Carriers
  • Malaria / drug therapy*
  • Male
  • Mice
  • Nanoparticles
  • Plasmodium berghei / drug effects*
  • Plasmodium berghei / isolation & purification
  • Polyphosphates / chemistry
  • Time Factors

Substances

  • Antimalarials
  • Drug Carriers
  • Polyphosphates
  • Chloroquine
  • Chitosan
  • triphosphoric acid