• Suman Ramteke School of Pharmaceutical Sciences, Rajiv Gandhi Proudyogiki, Vishwavidyalaya, Bhopal. 462036, Madhya Pradesh
  • Roshni Ubnare School of Pharmaceutical Sciences, Rajiv Gandhi Proudyogiki, Vishwavidyalaya, Bhopal. 462036, Madhya Pradesh
  • Naveneet Dubey School of Pharmaceutical Sciences, Rajiv Gandhi Proudyogiki, Vishwavidyalaya, Bhopal. 462036, Madhya Pradesh
  • Anjita Singh School of Pharmaceutical Sciences, Rajiv Gandhi Proudyogiki, Vishwavidyalaya, Bhopal. 462036, Madhya Pradesh


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.

Keywords: Solid lipid nanoparticles, Cerebral malaria, Intranasal administration, Artemether, Glyecerylmonosterate, Lecithin


Download data is not yet available.


1. Petersen E. Malaria chemoprophylaxis: when should we use it and what are the options? Expert Rev Anti-Infect Ther 2004;2:119–32.
2. Medana IM, Turner GDH. Human cerebral malaria and the blood-brain barrier. Int J Parasitol 2006;36:555–68.
3. WHO. Available from: a87017eng.pdf [Last accessed on 17 Jul 2007]
4. Karbwang J, Na-Bangchang K, Congpuong K, Molunto P, Thanavibul A. Pharmacokinetics and bioavailability of oral and intramuscular artemether. Eur J Clin Pharmacol 1997;52:307–10.
5. Hien TT, Davis TM, Chuong LV, Ilett KF, Sinh DX, Phu NH, et al. Comparative pharmacokinetics of intramuscular artesunate and artemether in patients with severe falciparum malaria. Antimicrob Agents Chemother 2004;48:4234–9.
6. Lin AJ, Ager JRAL, Klayman DL. Antimalarial activity of dihydroartemisinin derivatives by transdermal application. Am J Trop Med Hyg 1994;50:777–83.
7. Karunajeewa HA, Kemiki A, Alpers MP, Lorry K, Batty KT, Ilett KF, et al. Safety and therapeutic efficacy of artesunate suppositories for treatment of malaria in children in Papua new guinea. Pediatr Infect Dis J 2003;22:251–6.
8. Chow H, Anavy N, Villalobos A. Direct nose-brain transport of benzoylecgonine following intranasal administration in rats. J Pharm Sci 2001;90:1729-35.
9. Dufes C, Olivier JC, Gaillard F, Gaillard A, Couet W, Muller JM. Brain delivery of vasoactive intestinal peptide (vip) following nasal administration to rats. Int J Pharm 2003;255:87-97.
10. Pires PC, Santos AO. Nanosystems in nose-to-brain drug delivery: A review of non-clinical brain targeting studies. J Controlled Release 2018;270:89-100.
11. Lakshmi PK, Prasanthi D, Veeresh B. Non-invasive delivery of protein and peptide drugs: a review. Asian J Pharm Clin Res 2017;109:25-33.
12. Jogani VV, Shah PJ, Mishra P, Mishra AK, Misra AR. The intranasal mucoadhesive microemulsion of tacrine to improve brain targeting. Alzheimer Dis Assoc Disord 2008;22:116-24.
13. Mantry S, Balaji. Formulation design and characterization of ropinirole hydrochloride microsphere for intranasal delivery. Asian J Pharm Clin Res 2017;10:195-203.
14. Hashizume R, Ozawa T, Gryaznov SM, Bollen AW, Lamborn KR, Frey 2nd WH, et al. New therapeutic approach for brain tumors: intranasal delivery of telomerase inhibitor GRN163. Neurol Oncol 2008;10:112-20.
15. Sakane T, Yamashita S, Yata N, Sezaki H. Transnasal delivery of 5-fluorouracil to the brain in the rat. J Drug Target 1999;7:233-40.
16. Barakat NS, Omar SA, Ahmed AA. Carbamazepine uptake into rat brain following intra-olfactory transport. J Pharm Pharmacol 2006;58:63-72.
17. Westin U, Piras E, Jansson B, Bergström U, Dahlin M, Brittebo E, et al. Transfer of morphine along the olfactory pathway to the central nervous system after nasal administration to rodents. Eur J Pharm Sci 2005;24:565-73.
18. Yamada K, Hasegawa M, Kametani S, Ito S. Nose-to-brain delivery of ts-002, prostaglandin d2 analogue. J Drug Target 2007;15:59-66.
19. Jain K, Sood S, Gowthamarajan K. Optimization of artemether–loaded NCL for intranasal delivery using composit design. Drug Delivery 2014;22:1-15.
20. Ekambaram P, Sathali AA. Formulation and evaluation of solid lipid nanoparticles of ramipril. J Young Pharm 2011;3:216-20.
21. Shaw RS, Nihal M, Ahmad N. Dose translation from animal to human studies revisited. FASEB J 2007;22:659-66.
22. Muhia DK, Mberu EK, Watkins WM. Differential extraction of artemether and its metabolite dihydroartemisinin from plasma and determination by high-performance liquid chromatography. J Chromatography 1994;660:196-9.
23. Schwarz C. Solid lipid nanoparticles for controlled drug delivery II. Drug incorporation and physicochemical characterization. J Microencapsul 1999;16:205-13.
151 Views | 442 Downloads
How to Cite
Ramteke, S., R. Ubnare, N. Dubey, and A. Singh. “INTRANASAL DELIVERY OF ARTEMETHER FOR THE TREATMENT OF CEREBRAL MALARIA”. International Journal of Pharmacy and Pharmaceutical Sciences, Vol. 10, no. 9, Sept. 2018, pp. 9-14, doi:10.22159/ijpps.2018v10i9.25408.
Original Article(s)