Mohini Chaurasia1, Pankaj K Singh2, Anil K Jaiswal3, Animesh Kumar2, Vivek K Pawar2, Anuradha Dube3, Sarvesh K Paliwal4, Manish K Chourasia2. 1. Amity Institute of Pharmacy, Amity University, Lucknow, UP, 226 028, India. mohinichaurasia@gmail.com. 2. Pharmaceutics Division, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Lucknow, India, 226031. 3. Parasitology Division, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Lucknow, India, 226031. 4. Department of Pharmacy, Banasthali University, Banasthali, India, 304022.
Abstract
PURPOSE: 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). MATERIALS & METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
PURPOSE: 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). MATERIALS & METHODS: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. RESULTS: 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. CONCLUSIONS: 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: Sarah Jones; Catpagavalli Asokanathan; Dorota Kmiec; June Irvine; Roland Fleck; Dorothy Xing; Barry Moore; Roger Parton; John Coote Journal: Vaccine Date: 2013-10-10 Impact factor: 3.641
Authors: Pankaj K Singh; Anil K Jaiswal; Vivek K Pawar; Kavit Raval; Animesh Kumar; Himangsu K Bora; Anuradha Dube; Manish K Chourasia Journal: Pharm Res Date: 2018-02-09 Impact factor: 4.200
Authors: Natascia Bruni; Barbara Stella; Leonardo Giraudo; Carlo Della Pepa; Daniela Gastaldi; Franco Dosio Journal: Int J Nanomedicine Date: 2017-07-26