Coating doxorubicin-loaded nanocapsules with alginate enhances therapeutic efficacy against Leishmania in hamsters by inducing Th1-type immune responses.
Br J Pharmacol
; 171(17): 4038-50, 2014 Sep.
Article
en En
| MEDLINE
| ID: mdl-24837879
ABSTRACT
BACKGROUND AND PURPOSE:
The aim of the present study was to evaluate the immunomodulatory and chemotherapeutic potential of alginate-(SA) coated nanocapsule (NCs) loaded with doxorubicin (SA-NCs-DOX) against visceral leishmaniasis in comparison with nano-emulsions containing doxorubicin (NE-DOX). EXPERIMENTALAPPROACH:
NE-DOX was prepared using low-energy emulsification methods. Stepwise addition of protamine sulphate and SA in a layer-by-layer manner was used to form SA-NCs-DOX. SA-NCs-DOX, NE-DOX and Free DOX were compared for their cytotoxicity against Leishmania donovani-infected macrophages in vitro and generation of T-cell responses in infected hamsters in vivo. KEYRESULTS:
Size and ζ potential of the NE-DOX and SA-NCs-DOX formulations were 310 ± 2.1 nm and (-)32.6 ± 2.1 mV, 342 ± 4.1 nm and (-)29.3 ± 1.2 mV respectively. SA-NCs-DOX was better (1.5 times) taken up by J774A.1 macrophages compared with NE-DOX. SA-NCs -DOX showed greater efficacy than NE-DOX against intramacrophagic amastigotes. SA-NCs-DOX treatment exhibited enhanced apoptotic efficiency than NE-DOX and free DOX as evident by cell cycle analysis, decrease in mitochondrial membrane potential, ROS and NO production. T-cell responses, when assessed through lymphoproliferative responses, NO production along with enhanced levels of iNOS, TNF-α, IFN-γ and IL-12 were found to be up-regulated after SA-NCs-DOX, compared with responses to NE-DOXâ in vivo. Parasitic burden was decreased in Leishmania-infected hamsters treated with SA-NCs-DOX, compared with NE-DOX. CONCLUSIONS AND IMPLICATIONS Our results provide insights into the development of an alternative approach to improved management of leishmaniasis through a combination of chemotherapy with stimulation of the innate immune system.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
3_ND
Problema de salud:
3_zoonosis
Asunto principal:
Leishmania donovani
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Daunorrubicina
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Células TH1
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Materiales Biocompatibles Revestidos
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Alginatos
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Nanocápsulas
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Antiprotozoarios
Límite:
Animals
Idioma:
En
Revista:
Br J Pharmacol
Año:
2014
Tipo del documento:
Article
País de afiliación:
India