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https://hdl.handle.net/1822/41895
Título: | Delivery of LLKKK18 loaded into self-assembling hyaluronic acid nanogel for tuberculosis treatment |
Autor(es): | Silva, João P. Gonçalves, Carine Costa, C. Sousa, Jeremy Silva-Gomes, Rita Castro, António G. Pedrosa, Jorge Appelberg, Rui Gama, F. M. |
Palavras-chave: | Antimicrobial peptide Macrophages Infectious diseases Cathelicidin Mycobacteria |
Data: | 10-Jul-2016 |
Editora: | Elsevier |
Revista: | Journal of Controlled Release |
Citação: | Silva, João P.; Gonçalves, Carine; Costa, C.; Sousa, Jeremy; Silva-Gomes, Rita; Castro, António G.; Pedrosa, Jorge; Appelberg, Rui; Gama, F. M., Delivery of LLKKK18 loaded into self-assembling hyaluronic acid nanogel for tuberculosis treatment. Journal of Controlled Release, 235, 112-124, 2016 |
Resumo(s): | uberculosis (TB), a disease caused by the human pathogen Mycobacterium tuberculosis, recently joined HIV/AIDS on the top rank of deadliest infectious diseases. Low patient compliance due to the expensive, long-lasting and multi-drug standard therapies often results in treatment failure and emergence of multi-drug resistant strains. In this scope, antimicrobial peptides (AMPs) arise as promising candidates for TB treatment. Here we describe the ability of the exogenous AMP LLKKK18 to efficiently kill mycobacteria. The peptide's potential was boosted by loading into self-assembling Hyaluronic Acid (HA) nanogels. These provide increased stability, reduced cytotoxicity and degradability, while potentiating peptide targeting to main sites of infection. The nanogels were effectively internalized by macrophages and the peptide presence and co-localization with mycobacteria within host cells was confirmed. This resulted in a significant reduction of the mycobacterial load in macrophages infected in vitro with the opportunistic M. avium or the pathogenic M. tuberculosis, an effect accompanied by lowered pro-inflammatory cytokine levels (IL-6 and TNF-). Remarkably, intra-tracheal administration of peptide-loaded nanogels significantly reduced infection levels in mice infected with M. avium or M. tuberculosis, after just 5 or 10 every other day administrations. Considering the reported low probability of resistance acquisition, these findings suggest a great potential of LLKKK18-loaded nanogels for TB therapeutics. |
Tipo: | Artigo |
URI: | https://hdl.handle.net/1822/41895 |
DOI: | 10.1016/j.jconrel.2016.05.064 |
ISSN: | 0168-3659 |
Arbitragem científica: | yes |
Acesso: | Acesso aberto |
Aparece nas coleções: | CEB - Publicações em Revistas/Séries Internacionais / Publications in International Journals/Series ICVS - Artigos em revistas internacionais / Papers in international journals |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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document_38988_1.pdf | 2,71 MB | Adobe PDF | Ver/Abrir |