INTRANASAL DELIVERY OF ARTEMETHER FOR THE TREATMENT OF CEREBRAL MALARIA
Objective: Nasal delivery provides a route of entry of drug to the brain that circumvents the obstacle for blood-brain barrier allowing direct drug delivery to the central nervous system via olfactory neurons. The objective of work was to prepare solid lipid nanoparticles of antimalarial drug artemether for brain delivery through olfactory delivery route for treatment of cerebral malaria.
Methods: Artemether containing solid lipid nanoparticles were prepared with soya lecithin and poloxamer 407 with a hot homogenization method followed by solvent injection technique. The prepared solid lipid nanoparticles were characterized by their shape, particle size, zeta potential, encapsulation efficiency total drug content and drug release study.
Results: These solid lipid nanoparticles were observed spherical in shape in scanning electron microscopy, the optimized size was found to be 211.6 nm (Polydispersity Index PI<0.415), with âˆ’27mV zeta potential value. The maximum % yield of the formulation was found to be found 49%. The maximum entrapment efficiency was 82% (w/w), and optimized formulation showed 98.07Â±1.521% drug release form formulation. In vivo studied were conducted on wistar rats after administration of artemether containing solid lipid nanoparticles intranasally and compared with plain artemether solution administered orally. The results of optimized formulation showed the value of biological half-life (T1/2) was 4.95 h, maximum serum concentration Cmax was 644.60ng/ml, time for drug to reach peakÂ plasmaÂ concentration Tmax was 1 h volume of distribution (Vd) was 2.7l/kg, body clearance (Cl) was 0.37 lh/kg and Area under curve [AUC]0âˆž was 3970.5 nghr/ml for formulation.
Conclusion: The results revealed that the brain: plasma concentration ratio was higher after intranasal administration of solid lipid nanoparticles (SLNs) of artemether than the oral route. In conclusion, the intranasal administration of lipid nanoparticles of artemether could provide complete protection against cerebral malaria.
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