title: Chitosan-based macrophage-mediated drug targeting for the treatment of experimental visceral leishmaniasis.
abstract: The potential of chitosan microparticles as a carrier of doxorubicin for the treatment of visceral leishmaniasis was evaluated by macrophage-mediated drug targeting approach. Cationic charge of doxorubicin was masked by complexing it with dextran sulphate (a poly anion) in order to facilitate its incorporation into cationic chitosan microparticles. Prior to in vitro and in vivo studies, characterization studies were carried out systematically: particle size (∼1.049 µm), surface morphology (fluorescence microscopy - spherical structured microparticles), Fourier transform infrared spectroscopy (to characterize effective cross-linking) and differential scanning calorimetry. In vitro studies were carried out in J774.1 in order to check the effective endocytotic uptake of microparticles by macrophages. In vivo studies were conducted in Syrian golden hamsters as per well-established protocols and the results drawn from in vivo studies displayed substantial reduction in leishmanial parasite load for doxorubicin-encapsulated chitosan microparticles: ∼78.2 ± 10.4%, when compared to the control (free doxorubicin): 33.3 ± 2.4%.
authors.affiliation: Division of Pharmaceutics, Central Drug Research Institute, CSIR, Lucknow, Uttar Pradesh, India.
authors.forename: Sijumon
authors.initials: S
authors.lastname: Kunjachan
authors.forename: Swati
authors.initials: S
authors.lastname: Gupta
authors.forename: Anil K
authors.initials: AK
authors.lastname: Dwivedi
authors.forename: Anuradha
authors.initials: A
authors.lastname: Dube
authors.forename: Manish K
authors.initials: MK
authors.lastname: Chourasia
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics / Q000494:pharmacology*; D002460:Cell Line; D048271:Chitosan / Q000493:pharmacokinetics / Q000494:pharmacology*; D006224:Cricetinae; D004317:Doxorubicin / Q000493:pharmacokinetics / Q000494:pharmacology*; D004337:Drug Carriers / Q000493:pharmacokinetics / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D007898:Leishmaniasis, Visceral / Q000188:drug therapy*; D008264:Macrophages; D008647:Mesocricetus; D051379:Mice
chemical_list: D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D004317:Doxorubicin; D048271:Chitosan