Degradable Theranostic Polyurethane for Macrophage-Targeted Antileishmanial Drug Delivery

The present investigation aims to develop a reactive oxygen species (ROS) and esterase-responsive biodegradable mannosylated polyurethane to effectively deliver the encapsulated antileishmanial drug amphotericin B (AmB) selectively to infected macrophage cells. Owing to suitable amphiphilic balance, the as-synthesized glycosylated polyurethane (PU2M) with aryl boronic ester-based diol (M2) moiety as ROS-trigger, water-soluble mannose pendants, and fluorescent 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) chain ends for bioimaging formed nanoaggregates in an aqueous medium as confirmed by 1H NMR spectroscopy, dynamic light scattering (DLS), field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), and critical aggregation concentration (CAC) measurements. Aided by two endogenous stimuli present in phagolysosome, ROS and esterase, AmB-encapsulated polymeric nanoaggregates as drug delivery vehicles achieved an efficient reduction of both L. donovani and L. major intracellular amastigote burden compared to the free AmB. Overall, this work illustrated a promising therapeutic application of dual endogenous stimuli-triggered degradable theranostic polyurethane for target-specific drug delivery of AmB, to mitigate leishmaniasis.