Please use this identifier to cite or link to this item:
Title: Novel Approaches to the Treatment of the Rodent Malaria Parasite Plasmodium berghei In Vivo
Authors: Zelai, Noha Talal
Supervisors: Tobin, Andrew
Abuzinadyh, Najwa
First Published: 7-Sep-2017
Award date: 7-Sep-2017
Abstract: The rapid increase in malarial drug resistance and the severe side effects related to high doses of the current drugs have contributed to the urgent need for a new drug strategy to treat malaria. In situ gel implantation is used to increase the solubility of drugs, leading to higher absorption in the body. In addition, entrapping antimalarial drugs in nanocapsules has the potential to restore the use of older drugs with toxic side effects by modifying their bio-distribution, reducing their toxicity, and increasing their efficacy. The techniques used tested the effects of free drug, in situ gel systems, and nanocarrier formulations against malaria parasites. A formulation of 30% polymer to solvent was used as an in situ gel, holding one of the three malarial drugs tested. Our experiments demonstrate that the single dose in situ gel preparation leads to similar release as multiple doses of free drug. However, a 73%, 27%, and 100% cure rate was achieved with silver sulphadiazine, halofantrine, and chloroquine phosphate in situ gel, respectively. In contrast, a 0%, 0%, and 66.7% cure rate was achieved with the same drugs alone, respectively. However, late treatment did not result in the same effects observed for immediate treatment. In nanocarrier system, water-soluble chloroquine phosphate was prepared via double emulsion solvent evaporation, while nonwater-soluble halofantrine and silver sulphadiazine were prepared via interfacial polymer deposition. In vitro release studies showed slower silver sulphadiazine and chloroquine phosphate release in phosphate buffer saline media, when administered in nanocapsules than when administered in the free formulation. The antimalarial experiments showed 100% cure rate in both immediate and late infections. Nanocarriers are more efficacious than in situ gelling systems against malaria. This phenomenon is attributable to slow in vitro release as well as nanocarrier size, charge, and cellular uptake properties.
Type: Thesis
Rights: Copyright © the author. All rights reserved.
Appears in Collections:Leicester Theses
Theses, Dept. of Molecular and Cell Biology

Files in This Item:
File Description SizeFormat 
2017ZelaiNTPhD.pdfThesis3.23 MBAdobe PDFView/Open

Items in LRA are protected by copyright, with all rights reserved, unless otherwise indicated.