Studies on efficacy of niosomes for combinatorial drug delivery of antimalarial drugs

Abstract

Malaria is an important parasitic disease. Drugs used for the treatment and prevention of malaria are often plagued by the problem of development of resistance. This has hampered their therapeutic efficiency and rendered them ineffective for monotherapy. However, if re-packaged and combined properly, many of these neglected anti-malarial drugs can possibly find their way back into the treatment regime. The main goal of this thesis was to formulation new combinations of already existing drugs that exhibit a potent antimalarial effect. The drugs used in this thesis were primaquine diphosphate (PRI), curcumin (CMN) and artemether (ARM). The proposed combinations were then packaged within niosomes, and their in vivo anti-malarial efficacy for prevention of recrudescence when compared to their respective monotherapy options was assessed. newlineFirstly, a stability-indicating method for all three drugs used in this study was developed. Drugs were exposed to varying conditions such as acidic, basic, neutral, oxidation, photodegradation and heat in order to identify the conditions at which the drugs can degrade. Antimalarials are predominantly used in the tropical and sub-tropical regions of the world. These regions are known for their harsh climatic conditions. Hence, it is necessary to identify the effect of varying conditions in order to be able to use the excipients that could protect the drugs from degrading and thus proglong the shelf life of the formulations. It is observed that the conditions for which degradation was observed for all the three drugs is extremely harsh and generally not prevalent in the regions where these drugs will predominantly be used. newlineFurther, a precise, accurate and robust RP-HPLC method for the estimation of PRI, CMN and ARM was developed. This method will help to identify the drug concentrations in any formulations that will employ the proposed drug combinations studied in this thesis. newline