Probing a drug-drug based co-crystallization approach to study its impact on solubility, anti-leishmanial and anti-viral activities of Amphotericin B

Background Leishmaniasis continues to pose a major growing global public health challenge including Pakistan and Yemen. AmB is the standard drug for the treatment with limited clinical utility due to extremely low aqueous solubility, nephrotoxicity, and high cost. Therefore, alternative but equally effective formulation remains a pressing concern.Method In the present study, drug-drug co-crystallization approach successfully employed to modulate the physicochemical and biological properties of AmB without altering its molecular framework. Four new AmB co-crystals (2–5) were synthesized with FDA approved drugs as coformers.Results All co-crystals revealed significant enhancement in solubility, showed potent anti-leishmanial potential against promastigotes of L. major, L. tropica and L. donovani except co-crystal 5 as well as anti-viral potential against SARS-CoV-2. The results of L. major infected murine macrophage cellular assay and the AFM analysis further revealed the promising inhibitory potential against the L. major amastigotes as well. The synthesized co-crystals also showed significantly improved toxicity profiles in comparison to Amphotericin B.Conclusion The initial promising results of the improved anti-leishmanial, potential demonstrated that drug-drug based pharmaceutical co-crystallization may be a promising strategy for improving the therapeutic performance of AmB and therefore, worth to be explored further via detailed in vivo and pharmacokinetic studies.