Title: Nanotechnological advances in the treatment of leishmaniasis
Abstract:
Leishmaniasis, one of the most significant neglected tropical diseases worldwide, is caused by Leishmania parasites and is spread by sandfly bites. There are three main clinical forms of leishmaniasis: visceral (kala-azar), cutaneous, and mucocutaneous. Visceral leishmaniasis is the most serious form of leishmaniasis, while cutaneous leishmaniasis is the most common. Mucocutaneous leishmaniasis is the most debilitating form of this disease. The World Health Organization (WHO) estimates that 30,000 new cases of visceral leishmaniasis and 1 million new cases of cutaneous leishmaniasis are reported each year. Apart from the devastating social and economic impacts of the disease, especially in impoverished and developing countries, it also carries a financial burden owing to its global reach. Currently, there is no vaccine available to protect against leishmaniasis. Furthermore, the medications used to treat leishmaniasis (pentavalent antimonials [Glucantime®], sodium stibogluconate) [Pentostam®], and Amphotericin B) have severe side effects, considerable toxicity, necessitate hospitalization for parenteral administration, and require lengthy therapy regimens, making the treatment a complex and expensive process. Most significantly, these medications have limited therapeutic effectiveness, largely owing to the resistance of the parasite to the drugs. Nanocarriers offer a potential solution to these drawbacks, and are thus promising for drug delivery. Nanocarriers can transport both hydrophilic and hydrophobic drugs, potentially increasing the drug's stability, bioavailability, and therapeutic effectiveness, reducing side effects and toxicity, eliminating drug resistance, and allowing for the reformulation of existing drugs, as well as providing a controlled and gradual drug release. Nanocarriers composed of various components, including lipids, polymers, and carbon, have been developed for the treatment of leishmaniasis. These systems include liposomes, solid lipid nanoparticles, nanostructured lipid carriers, niosomes, nanoemulsions, polymeric micelles, dendrimers, polymeric nanoparticles, carbon nanotubes, magnetic nanoparticles, and metallic nanoparticles. However, only the liposomal form of Amphotericin B is commercially available. Liposomal Amphotericin B is currently the most advantageous option due to its decreased toxicity and enhanced therapeutic efficacy; however, it still has drawbacks such as its high cost and limited knowledge of pharmacodynamics and clinical data, particularly in young children and pregnant women. Efforts have been made to encapsulate nanocarriers with both existing drugs and novel active ingredients, including plant-derived compounds. Nevertheless, the high cost of commercializing and producing antileishmanial drug-containing nanocarriers on a large scale remains an issue that needs to be addressed.
