Solution blow spun polymeric nanofibres embedding cyclodextrin complexes of miltefosine: An approach to the production of sprayable dressings for the treatment of cutaneous leishmaniasis

Leishmaniasis is a neglected tropical disease caused by Leishmania genus protozoa. Treating this disease effectively and safely remains a significant challenge. Herein, hydroxypropyl-beta-cyclodextrin (HPβCD) and miltefosine (MF), an alkylphospholipid currently used for the treatment of leishmaniasis, were incorporated into nonwoven mats made of nanofibres of polyvinylpyrrolidone and the amphiphilic block copolymer Tetronic® 1307. The mats were produced in straightforward manner by solution blow spinning (SBS), after the optimisation of the experimental setup for the in-situ production. Scanning electron microscopy, FTIR spectroscopy, X-ray diffraction and differential scanning calorimetry were used to fully characterize the fibres morphology and structure. Both MF and HPβCD were embedded into the fibres at proportions adequate for the therapeutic action of MF, without affecting their global morphology. The release kinetics was controlled by the fast dissolution of the hygroscopic polymeric matrix. HPβCD-MF-loaded fibres demonstrated active against Leishmania promastigotes, displaying higher activity than MF, in addition to a reduced cytotoxicity in macrophages. The functionalised fibres affected the expression levels of parasite genes related to proliferation, differentiation, and drug response. This work demonstrates the potential of SBS for the in-situ delivery of drugs in the form of sprayable dressings, highlighting the use of CD complexes of antileishmanial agents.