Liposome-based nanocarrier loaded with a new quinoxaline derivative for the treatment of cutaneous leishmaniasis.

The use of nanocarriers for drug delivery is a strategy aimed to improve therapeutic indices through changes in their pharmacokinetic and pharmacodynamic characteristics. Liposomes are well-investigated nanocarriers for drug delivery to macrophage-targeted therapy, the main hosts of intracellular pathogens of some infectious diseases, such as leishmaniasis. In this study, we developed hyaluronic acid (HA)-coated liposomes by different methods that can encapsulate a new quinoxaline derivative, the LSPN331, to increase its solubility and improve its bioavailability. The surface modification of liposomes and their physicochemical characteristics may depend on the coating method, which may be a critical parameter with regard to the route of administration of the antileishmanial drug. Liposomes with identical phospholipid composition containing the same drug were developed, and different biological responses were verified, and our hypothesis is that it is related to the type of modification of the surface. Different physicochemical characterization techniques (dynamic light scattering, transmission electron microscopy and UV-vis quantification of labeled-HA) were used to confirm the successful modification of liposomes as well as their stability upon storage. The encapsulation of LSPN331 was performed using HPLC method, and the entrapment efficiency (EE%) was satisfatory in all formulations, considering results of similar formulations in the literature. Furthermore, in vitro and in vivo studies were carried out to evaluate the efficacy against the parasite Leishmania amazonensis. The in vitro activity was maintained or even improved and HA-coated liposomes showed the ability to target to the site of action by the proposed routes of administration, topically and intravenously. Both formulations are promising for future tests of antileishmania activity in vivo.