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

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.This work was supported by Fundo Europeu de Desen­volvimento Regional (FEDER) funds through the Opera­tional Competitiveness Program–COMPETE and by national funds through Fundação para a Ciência e a Tecnologia un­der projects FCOMP-01-0124-FEDER-015718 (PTDC/SAU-ENB/113151/2009). D Barros was supported by FCOMP-01- 0124-FEDER-015718 (PTDC/SAU-ENB/113151/2009) project. SA Costa Lima was supported by SFRH/BPD/37880/2007 and by QREN under contract NORTE-07-0124-FEDER-000067. The authors have no other relevant affiliations or financial involve­ment with any organization or entity with a financial inter­est in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed