Abstract
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 −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 98.07±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 peak plasma 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]0∞ 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.
Highlights
Malaria is an infectious disease caused by the Plasmodium genus of a protozoan parasite
The prepared nanoparticles were characterized for particle size, polydispersity index (PDI), zeta potential, entrapment efficiency, total dug content, percent yield and in vitro drug release study
The results revealed that when solid lipid nanoparticles (SLN) formulation of artemether containing 0.077 mg dose of drug was given through intranasal route showed higher concentration in cerebrospinal fluid (CSF) than artemether suspension (0.154 mg of dose) given orally, which again confirmed that through intranasal route artemther may directly reach the brain which reveals that formulations are effective at low dose and may be more effective than available marketed formulation
Summary
Malaria is an infectious disease caused by the Plasmodium genus of a protozoan parasite. The oral bioavailability of artemether is low (∼40%) due to its poor aqueous solubility and degradation in stomach acids [4] whereas intramuscular injection suffers from disadvantages such as pain on injection and; slow and erratic absorption on intramuscular administration [5] These shortcomings of therapy could be overcome by the development of navel carriers or by administration of a drug through alternative route like rectal or transdermal administration of antimalarials have been investigated [6,7]. These solid lipid nanoparticles would have great potential to deliver the drug to CNS and could show controlled drug release and site-specific drug targeting These new delivery strategies could increase the uptake of artemether in the infected brain and could improve the patient compliance and therapeutic index of treatment therapy
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