Abstract
The control of leishmaniases, a complex parasitic disease caused by the protozoan parasite Leishmania, requires continuous innovation at the therapeutic and vaccination levels. Chitosan is a biocompatible polymer administrable via different routes and possessing numerous qualities to be used in the antileishmanial strategies. This review presents recent progress in chitosan research for antileishmanial applications. 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.
Highlights
Leishmaniases are neglected tropical and sub-tropical diseases with an estimated 0.7 to 1 million new cases per year in nearly 100 endemic countries, caused by Leishmania spp., a protozoan parasite transmitted by the female Phlebotomine sandfly [1,2]
C-6 oxidized chitosan derivative obtained from chemical chitosan oxidation that had been degraded by enzymes systems such as endocellulase, hyaluronidase, hyaluronate lyase, chitinase, and other proteins, exhibited low antileishmanial activity against Leishmania infantum LIPA 137 with an IC50 value at 125 μg/mL, whereas the antibacterial activity was not significant at all [19]
A study was performed in BALB/c mice to evaluate the efficacy of nanochitosan films in the treatment of cutaneous leishmaniasis caused by an Iranian strain of Leishmania major [32]
Summary
Leishmaniases are neglected tropical and sub-tropical diseases with an estimated 0.7 to 1 million new cases per year in nearly 100 endemic countries, caused by Leishmania spp., a protozoan parasite transmitted by the female Phlebotomine sandfly [1,2]. Pentostam® ), liposomal amphotericin B (AmBisome® ; LampB), paromomycin used by parenteral route, and miltefosine (Impavido® ), the latter remaining the single orally active drug [3]. Most of these drugs have limitations of high cost, significant adverse effects, variable effectiveness and drug resistance (for the antimonials for VL in the Indian subcontinent [ISC]); only LampB currently.
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