| Title | Crucial CD8+ T-lymphocyte cytotoxic role in amphotericin B nanospheres efficacy against experimental visceral leishmaniasis |
| Publication Type | Journal Article |
| 2014 |
| Authors | Costa Lima, SA, Silvestre, R, Barros, D, Cunha, J, Baltazar, MT, Dinis-Oliveira, RJ, Cordeiro-da-Silva, A |
| Journal | Nanomedicine: Nanotechnology, Biology, and Medicine |
| Volume | 10 |
| Issue | 5 |
| Pagination | 1021 - 1030 |
| Date Published | 2014 |
| Amphotericin B, Immune-modulation, Poly(d,l-lactide-co-glycolide) nanospheres, Visceral leishmaniasis |
| This work aims to develop poly(d,l-lactide-co-glycolide) (PLGA)-nanospheres containing amphotericin B (AmB) with suitable physicochemical properties and anti-parasitic activity for visceral leishmaniasis (VL) therapy. When compared with unloaded-PLGA-nanospheres, the AmB-loaded PLGA-nanospheres displayed an increased particle size without affecting the polydispersity and its negative surface charge. AmB stability in the PLGA-nanospheres was >90% over 60-days at 30°C. The AmB-PLGA-nanospheres demonstrated significant in vitro and in vivo efficacy and preferential accumulation in the visceral organs. In addition, an immune-modulatory effect was observed in mice treated with AmB-PLGA-nanospheres, correlating with improved treatment efficacy. The in vitro cytotoxic response of the T-lymphocytes revealed that AmB-PLGA-nanospheres efficacy against VL infection was strictly due to the action of CD8+- but not CD4+-T lymphocytes. Overall, we demonstrate a crucial role for CD8+ cytotoxic T lymphocytes in the efficacy of AmB-PLGA nanospheres, which could represent a potent and affordable alternative for VL therapy. From the Clinical Editor: This study demonstrates a crucial role for CD8+ T lymphocytes in eliminating visceral leishmaniasis in a murine model by enhancing the cytotoxic efficacy of CD8+ T-cells via amphotericin-B-PLGA nanospheres, paving a way to a unique, potentially more potent and cost-effective therapeutic strategy. © 2014 Elsevier Inc. |
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