{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T14:15:44Z","timestamp":1780582544844,"version":"3.54.1"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,7,17]],"date-time":"2023-07-17T00:00:00Z","timestamp":1689552000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Antibiot."],"abstract":"<jats:p><jats:italic>Mycobacterium marinum<\/jats:italic> is a waterborne pathogen responsible for tuberculosis-like infections in cold-blooded animals and is an opportunistic pathogen in humans. <jats:italic>M. marinum<\/jats:italic> is the closest genetic relative of the <jats:italic>Mycobacterium tuberculosis<\/jats:italic> complex and is a reliable surrogate for drug susceptibility testing. We synthesized and evaluated two nanoparticle (NP) formulations for compatibility with rifampicin, isoniazid, pyrazinamide, and ethambutol (PIRE), the front-line antimycobacterial drugs used in combination against active tuberculosis infections. Improved <jats:italic>in vitro<\/jats:italic> antimicrobial activity was observed with encapsulated rifampicin alone or in a cocktail of drugs formulated through co-encapsulation in amphiphilic polyanhydride NPs. Broth antimicrobial testing revealed that the encapsulation of PIRE in NP resulted in a significant increase in antimicrobial activity, with the benefit over soluble formulations at biologically relevant concentrations ranging from &amp;gt;10 to &amp;gt;3,000 fold. <jats:italic>M. marinum-<\/jats:italic>infected human macrophages treated with NP-PIRE were cleared of viable bacteria in 48\u00a0h following a single treatment, representing a &amp;gt;4 log reduction in colony-forming units and a &amp;gt;2,000-fold increase in antimicrobial activity. The amphiphilic polyanhydride nanoparticles demonstrated the ability to co-encapsulate PIRE antibiotics and enhance their antimicrobial activity against <jats:italic>M. marinum<\/jats:italic> in infected macrophages in culture and <jats:italic>in vitro<\/jats:italic>. These data suggest that polyanhydride nanoparticles are a promising nanotherapeutic for combatting <jats:italic>Mycobacterium<\/jats:italic> infections through improved intracellular targeting of encapsulated antibiotics.<\/jats:p>","DOI":"10.3389\/frabi.2023.1162941","type":"journal-article","created":{"date-parts":[[2023,7,17]],"date-time":"2023-07-17T23:42:03Z","timestamp":1689637323000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Nanotherapeutic delivery of antibiotic cocktail enhances intra-macrophage killing of Mycobacterium marinum"],"prefix":"10.3389","volume":"2","author":[{"given":"Andrea M.","family":"Binnebose","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam S.","family":"Mullis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon L.","family":"Haughney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Balaji","family":"Narasimhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan H.","family":"Bellaire","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,7,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1186\/s13065-017-0295-z","article-title":"Novel drug targets for mycobacterium tuberculosis: 2-heterostyrylbenzimidazoles as inhibitors of cell wall protein synthesis","volume":"11","author":"Anguru","year":"2017","journal-title":"Chem. 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