Honors Theses

Date of Award

2018

Document Type

Undergraduate Thesis

Department

Pharmaceutics and Drug Delivery

First Advisor

Babu L. Tekwani

Relational Format

Dissertation/Thesis

Abstract

Malaria is a disease that has affected people throughout the world for centuries and is still responsible for over 200 million clinical cases per year. While a number of developed countries have eradicated the disease, its prevalence in tropical regions poses a significant global health challenge. The disease is caused by the Plasmodium genus, an obligate, intracellular parasite that is carried by the female Anopheles mosquito. While there are effective antimalarial drugs in clinical use, Plasmodium's resilient nature has allowed it to develop resistance to multiple drugs. This fact makes it imperative to seek out novel drugs to combat resistant strains. Combination therapies are one effective way to treat malaria and prevent the incidence of drug resistance. The most commonly used class of combination therapy is the Artemisinin Based Combination Therapy. However, there is evidence that artemisinin resistance could be occurring in the field. In this study, new combinations were tested between the standard antimalarial drugs namely, chloroquine (CQ) and artemisinin (ART) along with the experimental antimalarial drugs namely an artemisinin dimer oxime (DIOX) and NPC1161B (NPC) (an 8-aminoquinoline). The combinations were tested in vitro using the SYBR Green-I based fluorescence assay with a drug-resistant W2 strain of Plasmodium falciparum (P.f.) in a checkerboard assay template. Resistance of Pf (W2) towards CQ was confirmed. Both DIOX and NPC showed partial antagonistic effect on the antimalarial action of CQ and artemisinin. Further in vivo evaluation of these combinations in rodent malarial models would be important for confirmation of these results.

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