Surface functionalization of polymeric nanospheres modulates macrophage activation: relevance in Leishmaniasis therapy

Abstract

Aim: To characterize the production and application of carbohydrate functionalized poly(d,l-lactide-co-glycolide) (PLGA) nanospheres as immune-modulatory mediators in the treatment of visceral leishmaniasis (VL). Materials & methods: PLGA nanospheres were prepared by nanoprecipitation and surface functionalized with mannose, mannan or mannosamine moieties using a carbodiimide reaction. Flow cytometry and fluorescence microscopy revealed the interaction of these nanospheres with macrophages. Results: The nanocarriers were taken up by murine primary macrophages using clathrin-mediated endocytosis. Co-culture of macrophages with carbohydrate-functionalized nanospheres led to their activation and production of pro-inflammatory cytokines. One dose of amphotericin B-loaded on mannan-functionalized nanospheres resulted in an efficacy VL therapy. Conclusion: This approach provides a promising therapy for VL and a new therapeutic nanoplatform for obligate intracellular pathogens.