Essencial oil-based nanomedicines against trypanosomatides

MARIA JOSE MORILLA AND EDER LILIA ROMERO

Essencial oil-based and Nanotechnology for the cure of microbial diseases

CRC Press

Año: 2017; p. 258 - 277

Neglected Tropical Diseases (NTDs) are defined as diseases suffering from a lack of attention by the public health community. The NTDs are associated with poverty and neglected by media and policy makers, affecting more than one billion people?one-sixth of the world?s population-mostly in rural areas of low-income countries (WHO. Neglected diseases). In the Latin American and Caribbean (LAC) region, the NTDs are among the most common conditions afflicting the estimated 99 million people, who live on less than US$2 per day (Hotez et al. 2012), the burden of disease closely approximating or even exceeding that resulting from HIV/AIDS (Hotez et al. 2008). The lost ability to attend school or work, retardation of growth in children, impairment of cognitive skills anddevelopment in young children as well as on the health of girls and women are typical consequences of NTDs affecting endemic populations (Hotez et al. 2006, Hotez et al. 2009). Trypanosomiasis, parasitic infections caused by protozoans of the Trypanosomatid family (a diverse group of flagellatedparasites that show similar cellular structures and undergo morphological alterations during their life cycles), are considered NTDs (Doctors without borders and Drugs for Neglected Disease initiative).Trypanosomatids affect 20 million people and cause 100,000 deaths per year, primarily in the tropical and subtropical areas of the world (Stuart et al. 2008). Trypanosomatids cause the human diseases American trypanosomiasis (or Chagas disease), leishmaniasis, African trypanosomiasis (or sleeping sickness) and Surra, a disease affecting animals.The drugs available to treat Chagas disease, leishmaniasis and surra, are toxic and ineffective. The main drawback of current pharmacotherapy is the lack of treatments capable of selectively and safely eliminating intracellular parasites. Long term treatments are required, that in case of leishmaniasismay generate resistance and can be expensive. Developing new specific parasiticidal drugs on the other hand, is a long and highly costly process that, because of the lack of economical profit, no pharmaceutical company consider worth to face (Wilkinson and Kelly 2009).One approach to circumvent the development of specific new drugs would be to screen the parasiticidal activity of different Essential Oils (EOs). Since ancient times, EOs have been widely used to relieve a wide variety of human maladies including bronchitis, pneumonia, pharyngitis,diarrhea, periodontal disease, wounds, because of their analgesic, sedative and anti-inflammatoryactivity (Gurib-Fakim 2006, Handbook of essential oils 2012). EOs also hold other relevant medicinal properties such as bactericidal, virucidal, fungicidal, antiparasitical and insecticidal activity (Burt 2004). EOs, however, are volatile, insoluble in water and easily decompose, owing to direct exposure to heat, humidity, light or oxygen (Turek and Stintzing 2013). Another major issue is their low oral bioavailability (Sharma et al. 2004, Anand et al. 2007).As defined by the International Organization for Standardization (ISO), the term ?essential oil? is reserved for a ?product obtained from vegetable raw material, either by distillation with water or steam, or from the epicarp of citrus fruits by a mechanical process, or by dry distillation? (ISO 9235, 1997), that is, by physical means only. Essential oils (EOs) are volatile, natural, aromatic oily liquids that can be obtained from several parts of the plants especially the aerial ones as leaves and flowers. They are derived from complex metabolic pathways to protect the plant organism from diverse pathogenic microorganisms, to repel insects that act as plague vectors, to reduce the appetiteof some herbivorous by conferring unpleasant taste to the plant (Bakkali et al. 2008). Constituents are lipophilic and highly volatile secondary plant metabolites, reaching a mass below a molecular weight of 300 Da, that can be physically separated from other plant components or membranous tissue (Sell 2010). The EOs are generally complex mixtures that include hydrocarbons (terpenes and sesquiterpenes) and oxygenated compounds (alcohols, esters, ethers, aldehydes, ketones, lactones, phenols and phenol ethers) (Guenther 1972). A significant amount of toxicity data is available for not only the oils but also the individual components such that many are generally regarded as safe (GRAS) by the FDA. GRAS status has permitted the use of EOs as flavouring agents in food and as additives to cosmetics, perfumes and cleaning products (Boire et al. 2013).The constituents of EOs act synergistically (phyto-synergic interactions) by different mechanisms which significantly reduce the possibility of occurrence of resistance. The synergism may involve the protection of an active substance from degradation by enzymes from the pathogen or the circumvention of numerous multi-drug resistance mechanisms based on ionic bomb-mediated expulsion of antibiotic molecules (Bassolé and Juliani 2012).Nanomedicines, on the other hand, are a powerful tool to selectively target a drug, to reduce its toxicity, and to increase its efficacy. Nanomedicines may also solve the classical problems of physical stability, low solubility, low permeability and bioavailability of EOs. The aim of this chapter is to provide an overview on the preclinical applications of EO (or some of their isolated components) based-nanomedicines used as trypanocidal agents, discussing the pros and cons of each experimental approach as well the feasibility of its future translation.