The control of leishmaniases, a complex parasitic disease caused by the protozoan parasite Leishmania, requires continuous innovation at the therapeutic and vaccine levels. Thus, the classical drugs are toxic and generate drug resistance. These limitations are also the consequence of a non adapted biodistribution of the active principles. Chitosan is a biocompatible polymer administrable via different routes and possessing numerous qualities to be used in the antileishmanial strategies. This entry presents recent progress in chitosan research for antileishmanial applications.
Leishmaniases are neglected tropical and sub-tropical diseases with an estimated 0.7-1 million new cases per year in nearly 100 endemic countries, caused by Leishmania spp, a protozoan parasite transmitted by the female Phlebotomine sandfly. About twenty Leishmaniaspecies are able to infect humans and two main clinical manifestations are usually described : visceral leishmaniasis (VL) that is fatal in the absence of treatment and which also affects dogs, and cutaneous leishmaniasis (CL), which is self-curing but leads to disfigurement and stigmatisation. There are other clinical manifestations of CL including mucocutanous and diffuse forms. Whereas some vaccines exist for dogs, with uncomplete efficacy, none are marketed for human use. Chemotherapy is presently the single approach to manage these diseases, which in combination with a more intense vector control.
This entry aims to present the most recent findings from the literature considering chitosan and its derivatives in different formulations for both therapeutic and vaccine purposes in the treatment and prevention of both cutaneous and visceral leishmaniasis.
First data on the mechanism of action of chitosan revealed an optimal in vitro intrinsic activity at acidic pH, high-molecular-weight chitosan being the most efficient form, with an uptake by pinocytosis and an accumulation in the parasitophorous vacuole of Leishmania-infected macrophages. In addition, the immunomodulatory effect of chitosan is an added-value both for the treatment of leishmaniasis and the development of innovative vaccines. The advances in chitosan chemistry allows pharmacomodulation on amine groups opening various opportunities for new polymers of different size, and physico-chemical properties adapted to the chosen routes of administration. Different formulations have been studied in experimental leishmaniasis models to cure visceral and cutaneous leishmaniasis, and chitosan can act as a booster through drug combinations with classical drugs, such as amphotericin B. The various architectural possibilities given by chitosan chemistry and pharmaceutical technology pave the way for promising further developments.
The chemical structure of chitosan is presented in Figure 1.
Figure 1. Chemical structure of chitosan polymer.
This entry is adapted from the peer-reviewed paper 10.3390/molecules25184123