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Many bacteria have evolved to become resistant to conventional antibiotherapy, representing a health and economic burden for those afflicted. The search for alternative and complementary therapeutic approaches has intensified and revived phage therapy. In recent decades, the exogenous use of lysins, encoded in phage genomes, has shown encouraging effectiveness. These two antimicrobial agents reduce bacterial populations; however, many barriers challenge their prompt delivery at the infection site. Encapsulation in delivery vehicles provides targeted therapy with a controlled compound delivery, surpassing chemical, physical and immunological barriers that can inactivate and eliminate them. This review explores phages and lysins' current use to resolve bacterial infections in the respiratory, digestive and integumentary systems. We also highlight the different challenges they face in each of the three systems and discuss the advances towards a more expansive use of delivery vehicles.<\/jats:p>","DOI":"10.1093\/femsre\/fuab019","type":"journal-article","created":{"date-parts":[[2021,3,26]],"date-time":"2021-03-26T12:09:38Z","timestamp":1616760578000},"source":"Crossref","is-referenced-by-count":44,"title":["The clinical path to deliver encapsulated phages and lysins"],"prefix":"10.1093","volume":"45","author":[{"given":"Ana Mafalda","family":"Pinto","sequence":"first","affiliation":[{"name":"Centre of Biological Engineering, LIBRO - Laborat\u00f3rio de Investiga\u00e7\u00e3o em Biofilmes Ros\u00e1rio Oliveira, Campus de Gualtar, 4719-057 Braga, Portugal"},{"name":"INL - International Iberian Nanotechnology Laboratory, Avenida Mestre Jos\u00e9 Veiga, 4715-330 Braga, Portugal"}]},{"given":"Maria Daniela","family":"Silva","sequence":"additional","affiliation":[{"name":"Centre of Biological Engineering, LIBRO - Laborat\u00f3rio de Investiga\u00e7\u00e3o em Biofilmes Ros\u00e1rio Oliveira, Campus de Gualtar, 4719-057 Braga, Portugal"},{"name":"INL - International Iberian Nanotechnology Laboratory, Avenida Mestre Jos\u00e9 Veiga, 4715-330 Braga, Portugal"}]},{"given":"Lorenzo M","family":"Pastrana","sequence":"additional","affiliation":[{"name":"INL - International Iberian Nanotechnology Laboratory, Avenida Mestre Jos\u00e9 Veiga, 4715-330 Braga, Portugal"}]},{"given":"Manuel","family":"Ba\u00f1obre-L\u00f3pez","sequence":"additional","affiliation":[{"name":"INL - International Iberian Nanotechnology Laboratory, Avenida Mestre Jos\u00e9 Veiga, 4715-330 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8408-8550","authenticated-orcid":false,"given":"Sanna","family":"Sillankorva","sequence":"additional","affiliation":[{"name":"INL - International Iberian Nanotechnology Laboratory, Avenida Mestre Jos\u00e9 Veiga, 4715-330 Braga, Portugal"}]}],"member":"286","published-online":{"date-parts":[[2021,3,30]]},"reference":[{"key":"2022033000005220700_bib1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2017\/5095293","article-title":"Skin immune landscape: inside and outside the organism","volume":"2017","author":"Abdallah","year":"2017","journal-title":"Mediators Inflamm"},{"key":"2022033000005220700_bib2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/21597081.2015.1020260","article-title":"Phage therapy of pulmonary infections","volume":"5","author":"Abedon","year":"2015","journal-title":"Bacteriophage"},{"key":"2022033000005220700_bib3","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.ejpb.2016.11.034","article-title":"Food, gastrointestinal pH, and models of oral drug absorption","volume":"112","author":"Abuhelwa","year":"2017","journal-title":"Eur J Pharm Biopharm"},{"key":"2022033000005220700_bib4","article-title":"Long term bacteriophage preservation","author":"Ackermann","year":"2004","journal-title":"WFCC Newsl"},{"key":"2022033000005220700_bib5","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1038\/s41551-018-0263-5","article-title":"Inhaled bacteriophage-loaded polymeric microparticles ameliorate acute lung infections","volume":"2","author":"Agarwal","year":"2018","journal-title":"Nat Biomed Eng"},{"key":"2022033000005220700_bib6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/femspd\/ftx042","article-title":"Insights on persistent airway infection by non-typeable Haemophilus influenzae in chronic obstructive pulmonary disease","volume":"75","author":"Ahearn","year":"2017","journal-title":"Pathog Dis"},{"key":"2022033000005220700_bib7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1128\/mBio.00029-12","article-title":"Bacteriophages \u03d5MR299-2 and \u03d5NH-4 can eliminate Pseudomonas aeruginosa in the murine lung and on cystic fibrosis lung airway cells. 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