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TitleDelivery of LLKKK18 loaded into self-assembling hyaluronic acid nanogel for tuberculosis treatment
Author(s)Silva, João P.
Gonçalves, Carine
Costa, C.
Sousa, Jeremy
Silva-Gomes, Rita
Castro, António G.
Pedrosa, Jorge
Appelberg, Rui
Gama, F. M.
KeywordsAntimicrobial peptide
Infectious diseases
Issue date10-Jul-2016
JournalJournal of Controlled Release
CitationSilva, 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
Abstract(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.
AccessOpen access
Appears in Collections:CEB - Publicações em Revistas/Séries Internacionais / Publications in International Journals/Series
ICVS - Artigos em Revistas Internacionais com Referee

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