Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 3 de 3
Filter
Add more filters










Database
Language
Publication year range
1.
Exp Parasitol ; 198: 79-86, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30769018

ABSTRACT

Cystic echinococcosis (CE), which is caused during the metacestode larval stage of Echinococcus granulosus, is a life-threatening disease and is very difficult to treat. At present, the FDA-approved antihelmintic drugs are mebendazole (MBZ), albendazole (ABZ) and its principal metabolite ABZ sulfoxide (ABZSO), but as these have a therapeutic efficacy over 50%, underlining the need for new drug delivery systems. The aim of this work was the optimization and characterization of previously developed ABZ lipid nanocapsules (ABZ-LNCs) and evaluate their efficacy in mice infected with E. granulosus. LNCs were prepared by the phase inversion technique and characterized in terms of size, surface charge, drug loading, and in vitro stability followed by an in vivo proof-of-concept using a murine model infected with E. granulosus. Stable particle dispersions with a narrow size distribution and high efficiency of encapsulation (≥90%) were obtained. ABZ-LNCs showed a greater chemoprophylactic efficacy than ABZ suspension administered by the oral route as 4 out of the 10 ABZ-LNCs treated mice did not develop any cysts, whereas the infection progressed in all mice from the ABZ suspension group. Regarding the ultrastructural studies of cysts, mice treated with ABZ-LNCs or ABZ suspension revealed changes in the germinal layer. However, the extent of the damage appeared to be greater after ABZ-LNC administration compared to the suspension treatment. These results suggest that ABZ-LNCs could be a promising novel candidate for ABZ delivery to treat CE.


Subject(s)
Albendazole/therapeutic use , Anticestodal Agents/therapeutic use , Echinococcosis/drug therapy , Echinococcus granulosus/drug effects , Albendazole/administration & dosage , Albendazole/chemistry , Animals , Anticestodal Agents/administration & dosage , Anticestodal Agents/chemistry , Cattle , Chromatography, High Pressure Liquid , Echinococcosis/prevention & control , Echinococcus granulosus/ultrastructure , Female , Intestines/chemistry , Mice , Microscopy, Electron, Scanning , Nanocapsules/standards , Nanocapsules/ultrastructure , Neglected Diseases/drug therapy , Neglected Diseases/prevention & control , Particle Size , Powders , Stomach/chemistry
2.
J Control Release ; 214: 12-22, 2015 Sep 28.
Article in English | MEDLINE | ID: mdl-26188153

ABSTRACT

Modern subunit vaccines require the development of new adjuvant strategies. Recently, we showed that CpG-ODN formulated with a liquid crystal nanostructure formed by self-assembly of 6-O-ascorbyl palmitate (Coa-ASC16) is an attractive system for promoting an antigen-specific immune response to weak antigens. Here, we showed that after subcutaneous injection of mice with near-infrared fluorescent dye-labeled OVA antigen formulated with Coa-ASC16, the dye-OVA was retained at the injection site for a longer period than when soluble dye-OVA was administered. Coa-ASC16 alone elicited a local inflammation, but how this material triggers this response has not been described yet. Although it is known that some materials used as a platform are not immunologically inert, very few studies have directly focused on this topic. In this study, we explored the underlying mechanisms concerning the interaction between Coa-ASC16 and the immune system and we found that the whole inflammatory response elicited by Coa-ASC16 (leukocyte recruitment and IL-1ß, IL-6 and IL-12 production) was dependent on the MyD88 protein. TLR2, TLR4, TLR7 and NLRP3-inflammasome signaling were not required for induction of this inflammatory response. Coa-ASC16 induced local release of self-DNA, and in TLR9-deficient mice IL-6 production was absent. In addition, Coa-ASC16 revealed an intrinsic adjuvant activity which was affected by MyD88 and IL-6 absence. Taken together these results indicate that Coa-ASC16 used as a vaccine platform is effective due to the combination of the controlled release of antigen and its intrinsic pro-inflammatory activity. Understanding how Coa-ASC16 works might have significant implications for rational vaccine design.


Subject(s)
Adjuvants, Immunologic/chemistry , Antigens/administration & dosage , Ascorbic Acid/analogs & derivatives , Myeloid Differentiation Factor 88/metabolism , Vaccines/administration & dosage , Animals , Ascorbic Acid/chemistry , Delayed-Action Preparations , Humans , Inflammasomes/drug effects , Inflammation/chemically induced , Inflammation/pathology , Interleukins/biosynthesis , Leukocytes/drug effects , Liquid Crystals , Mice , Mice, Knockout , Myeloid Differentiation Factor 88/genetics , Ovalbumin/immunology , Toll-Like Receptor 9/biosynthesis , Toll-Like Receptor 9/genetics , Toll-Like Receptors/biosynthesis
3.
Biomaterials ; 35(8): 2529-42, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24382332

ABSTRACT

The adjuvants approved in human vaccine with recombinant/purified antigens induce weak cellular immune response and so the development of new adjuvant strategies is critical. CpG-ODN has successfully been used as an adjuvant (phase I-III clinical trials) but its bioavailability needs to be improved. We investigated the adjuvant ability of CpG-ODN formulated with a liquid crystal nanostructure of 6-O-ascorbyl palmitate (Coa-ASC16). Mice immunized with OVA/CpG-ODN/Coa-ASC16 elicited a potent specific IgG1, IgG2a, Th1 and Th17 cellular response without systemic adverse effects. These responses were superior to those induced by OVA/CpG-ODN (solution of OVA with CpG-ODN) and to those induced by the formulation OVA/CpG-ODN/Al(OH)3. Immunization with OVA/CpG-ODN/Coa-ASC16 resulted in a long-lasting cell-mediated immune response (at least 6.5 months). Furthermore, Coa-ASC16 alone allows a controlled release of CpG-ODN in vitro and induces local inflammatory response, independent of TLR4 signaling, characterized by an influx of neutrophils and Ly6C(high) monocytes and pro-inflammatory cytokines. Remarkably, the adjuvant capacity of CpG-ODN co-injected with Coa-ASC16 (OVA/CpG-ODN plus Coa-ASC16) was similar to the adjuvant activity of OVA/CpG-ODN, supporting the requirement for whole formulation to help CpG-ODN adjuvanticity. These results show the potential of this formulation, opening a new avenue for the development of better vaccines.


Subject(s)
Adjuvants, Immunologic/pharmacokinetics , Immunity, Cellular , Liquid Crystals/chemistry , Oligodeoxyribonucleotides/pharmacokinetics , Adjuvants, Immunologic/chemistry , Alanine Transaminase/blood , Animals , Antigens/immunology , Ascorbic Acid/analogs & derivatives , Ascorbic Acid/chemistry , Ascorbic Acid/pharmacokinetics , Aspartate Aminotransferases/blood , Biological Availability , Cells, Cultured , Female , Immunization , Immunoglobulin G/immunology , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Nanostructures/chemistry , Oligodeoxyribonucleotides/chemistry , Ovalbumin/immunology , Signal Transduction , Spleen/cytology , Spleen/metabolism , Toll-Like Receptor 4/genetics , Toll-Like Receptor 4/metabolism , Vaccines/chemistry , Vaccines/immunology
SELECTION OF CITATIONS
SEARCH DETAIL
...