Delivery of LLKKK18 loaded into self-assembling hyaluronic acid nanogel for tuberculosis treatment

作者: João P. Silva , Carine Gonçalves , César Costa , Jeremy Sousa , Rita Silva-Gomes

DOI: 10.1016/J.JCONREL.2016.05.064

关键词: Human pathogenTuberculosisCytotoxicityAntimicrobial peptidesNanogelMycobacterium tuberculosisCathelicidinCytokineMicrobiologyMedicine

摘要: Tuberculosis (TB), a disease caused by the human pathogen Mycobacterium tuberculosis, recently joined HIV/AIDS on top rank of deadliest infectious diseases. Low patient compliance due to expensive, long-lasting and multi-drug standard therapies often results in treatment failure emergence resistant strains. In this scope, antimicrobial peptides (AMPs) arise as promising candidates for TB treatment. Here we describe ability exogenous AMP LLKKK18 efficiently kill mycobacteria. The peptide's potential was boosted loading into self-assembling Hyaluronic Acid (HA) nanogels. These provide increased stability, reduced cytotoxicity degradability, while potentiating peptide targeting main sites infection. nanogels were effectively internalized macrophages presence co-localization with mycobacteria within host cells confirmed. This resulted significant reduction mycobacterial load infected vitro opportunistic M. avium or pathogenic an effect accompanied lowered pro-inflammatory cytokine levels (IL-6 TNF-α). Remarkably, intra-tracheal administration peptide-loaded significantly infection mice after just 5 10 every other day administrations. Considering reported low probability resistance acquisition, these findings suggest great LLKKK18-loaded therapeutics.

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