| dc.description.abstract | Artemisinin and its derivatives have proved to be very effective against malaria parasites although it has the short falls of low solubility, poor bioavailability and short half-lives. Instead of discarding these drugs it is necessary to reformulate these drugs using nanomedicine drug delivery system to minimize if possible eradicate these problems. Thus the objectives of this study were to nanoformulate the anti-malaria drugs into selected nanocarriers and perform pre-clinical evaluation on the nanoformulated drugs against malaria parasites. This was done by encapsulating the primaquine (PQ) and dihydroartemisinin (DI--IA) into solid lipid nanoparticles (SLNs) using emulsification solvent evaporation technique while KAE 609 was loaded into liposomes composed of natural phospholipids through high pressure homogenization. The nanoformulated drugs were then characterized for Particle size, size distribution and zeta potential. The morphology of the nanoparticles was analyzed using a scanning electron microscope and Fourier Transform Infrared. The In vitro antiplasmodial activity of the free drugs and the nanoformulated drugs were evaluated against chloroquine-resistant strains of P. falciparum while In vivo efficacy of the free drugs and the nanoformulated drugs were conducted in mice infected with malaria parasite using the 4-day suppressive test. The mean particle size, zeta potential, drug loading, and encapsulation efficiency of the (PQ-SLNs) were 236 nm, +23 mV, 14%, and 75%, respectively. A spherical morphology of PQ-SI.Ns was seen by scanning electron microscope. In vitro, release profile depicted a steady drug release over 72 hours. The nanoformulated PQ was 20% more effective as compared with conventional oral dose when tested in Plasmodium herghei-infected Swiss albino mice O1--!A-SLNs showed desirable particle characteristics as a NMDDS including particle size (256.4 nm), particle surface charge (+ 19.0 mV), drug loadings ( 13.9 wt %), encapsulation efficacy (62.3%), polydispersion index (0.18) and a spherical appearance. The spray dried DHA-SLNs showed storage stability up to 90 days and a sustained slow release of drug over 25 hrs. Enhanced in vitro (IC50 value of 0.25 ng/ml) and in vivo (96.2% chemosuppression at 2 mg/kg/day) anti¬malarial activity was observed. The enhancement in efficacy was 14% when compared to that of free DHA. KAE609 was solubilized by encapsulating the drug into liposomes and the mean particle size for the optimized formulation was 78nm with an encapsulation efficiency of 100%. This study demonstrated that PQ and DHA can be encapsulated into SLNs for enhanced efficacy and a controlled, sustained release profile. On the other hand KAE609 can be solubilized using liposornes for parenteral drug delivery. | en_US |