Potency of Solid Lipid Nanoparticle (SLN)-Modified Luteolin-based Polyethylene Glycol (PEG) on Allium fistulosum as Innovation Therapy of Malaria Falciparum
In 2013, 198 million cases of malaria were reported globally and 584,000 of them died. As much as 78% of cases occurred in children under five years of age. Indonesia is a has the second highest malaria incidence rate after India in the Asian region. Severe malaria can be characterized by the presence of severe anaemia, hyperparasitemia or cerebral malaria. Severe anaemia due to malaria or severe malaria anaemia (SMA) often occurs in children who suffer from falciparum malaria. SMA occurs due to a decrease in COX-2-PGE2, caused by phagocytosis of PfHz (Plasmodium falciparumderived Hemozoin) by monocytes, macrophages and neutrophils. PfHz is a crystalline compound formed from the aggregation of heme hosts. Fe2+ is one of the constituents of heme, luteolin can bind Fe2+ so that the bond between luteolin and Fe2+ in heme prevents the formation of PfHz, so that severe anaemia can be prevented. Like other naturally occurring active compounds, luteolin has low bioavailability in the body so it is encapsulated using Solid Lipid Nanoparticles (SLN) and Polyethylene Glycol (PEG). SLN is useful for increasing the bioavailability of luteolin in the body, while PEG is useful for preventing the destruction of luteolin-SLN by RES. The modified construction process includes the following steps: (1) luteolin extraction from Allium fistulosum and (2) luteolin encapsulation using SLN-PEG. The potential dose to be administered orally to humans is 2.43–8.11 µg/kg body weight.
Keywords: luteolin, polyethylene glycol, severe malaria anaemia, solid lipid nanoparticles
 World Health Organization. (2013). Causes of Child Mortality. Retrieved from https://www.who.int/gho/ child_health/mortality/causes/en/.
 World Malaria Day. (2015, January). Retrieved December 12, 2020 from https://www.worldmalariaday. org/about/key-facts.
 Roll Back Malaria. (2014, January). Retrieved December 12, 2020 from http://www.rollbackmalaria.org/ countries/endemic-countries-1.
 Perkins, D. J., et al. (2011). Severe Malarial Anemia: Innate Immunity and Pathogenesis. International Journal of Biological Sciences, vol. 7, issue 9, pp. 1427–1442.
 Olivier, M., et al. (2010). Malarial Pigment Hemozoin and the Innate Inflammatory Response. Frontiers in Immunology, vol. 12, issue 12, pp. 889-99.
 Anyona, S. B., et al. (2012). Reduced Systemic Bicyclo-Prostaglandin-E2 and Cyclooxygenase-2 Gene Expression are Associated with Inefficient Erythropoiesis and Enhanced Uptake of Monocytic Hemozoin in Children with Severe Malarial Anemia. American Journal of Haematology, vol. 87, issue 8, pp. 782-89.
 Miean, K. H. and Mohames, S. (2001). Flavonoid (Myricetin, Quercetin, Kaempferol, Luteolin, and Apigenin) Content of Edible Tropical Plants. Journal of Agricultural and Food Chemistry, vol. 49, issue 6, pp. 3106-12.
 Nazari, Q. A., et al. (2013). Protective Effect of Luteolin on an Oxidative-Stress Model Induced by Microinjection of Sodium Nitroprusside in Mice. Journal of Pharmacological Sciences, vol. 122, issue 2, pp. 109-17.
 Deng, Y., et al. (2014). Luteolin- Loaded Solid Lipid Nanoparticles Synthesis, Characterization, & Improvement of Bioavailability, Pharmacokinetics in Vitro And Vivo Studies. Journal of Nanoparticle Research, vol. 16, issue 4, pp. 2346-55.
 Under, M. and Yener, G. (2007). Importance of Solid Lipid Nanoparticles (SLN) in Various Administration Routes and Future Perspectives. International Journal of Nanomedicine, vol. 2, issue 3, pp. 289-300.
 World Health Organization. (2011). The World Malaria Report 2011 Summarizes Information. Retrieved from https://www.who.int/malaria/world_malaria_report_2011/en/.
 Ong’echa, J. M., et al. (2008). Increased Circulating Interleukin (IL)-23 in Children with Malarial Anemia: In Vivo and In Vitro Relationship with Co-Regulatory Cytokines IL-12 and IL-10. Clinical Immunology, vol. 126, issue 2, pp. 211-21.
 Dirscher, M., et al. (2012). Luteolin Triggers Global Changes in the Microglial Transcriptome Leading to a Unique Anti-Inflammatory and Neuroprotective Phenotype. Journal of Neuroinflammation, vol. 7, issue 3, pp. 1-16.
 National Center for Biotechnology Information. (2015). Luteolin. Retrieved from https://pubchem.ncbi. nlm.nih.gov/compound/luteolin.
 Lin, Y., Shi, R., Wang, X., & Shen, H. M Shi, Wang, dan Shen. (2008). Luteolin, a Flavonoid with Potentials for Cancer Prevention and Therapy. Current Cancer Drug Targets, vol. 8, issue 7, pp. 634–646.
 Miean, K. H. and Mohamed, S. (2001). Flavonoid (Myricetin, Quercetin, Kaempferol, Luteolin, And Apigenin) Content of Edible Tropical Plants. Journal of Agricultural and Food Chemistry, vol. 49, issue 6, pp. 3106-12.
 Hanen, N., et al. (2014). Allium Species, Ancient Health Food for the Future. Retrieved from http: //cdn.intechopen.com/pdfs-wm/27393.pdf.
 Reedy, C. J., Elvekrog, M. M. and Gibney, B. R. (2008). Development of a Heme Protein Structure– Electrochemical Function Database. Nucleic Acids Research, vol. 36, issue 1, pp. 307-13.
 Loizzo, M. R., et al. (2007). Inhibition of Angiotensin Converting Enzyme (ACE) by Flavonoids Isolated from Ailanthus excelsa (Roxb) (Simaroubaceae). Phytotherapy Research, issue 21, pp. 32-36.
 Wan, F., et al. (2008). Studies on PEG Modified SLNs Loading Vinorelbine Bitartrate (I): Preparation and Evaluation in Vitro. International Journal of Pharmaceutic, vol. 359, issue 1-2, pp. 104-10.
 Swindle, M. M., et al. (2012). Swine as Models in Biomedical Research and Toxicology Testing. Veterinary Pathology, vol. 49, issue 2, pp. 344-56.
 Mukherjee, S., Ray, S. and Thakur, R. S. (2009). Solid Lipid Nanoparticles: A Modern Formulation Approach in Drug Delivery System. Indian Journal of Pharmaceutical Sciences, vol. 71, issue 4, pp. 349-58.
 Lazaro, M. (2009). Distribution and Biological Activities of the Flavonoid Luteolin. Medical Chemistry, issue 9, pp. 31-59.
 Leonarduzzi, G., et al. (2010). Design and Development of Nanovehicle Based Delivery System for Preventive or Therapeutic Supplementation with Flavonoid. Current Medical Chemistry, vol. 17, issue 1, pp. 74-95.
 Das, S. and Chaudhury, A. (2011). Recent Advances in Lipid Nanoparticle Formulation with Solid Matrix for Oral Drug Delivery. Pharmaceutical Science and Technology, vol.12, issue 1, pp. 62-76.