{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T00:50:56Z","timestamp":1775868656658,"version":"3.50.1"},"reference-count":27,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,1,17]],"date-time":"2020-01-17T00:00:00Z","timestamp":1579219200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011929","name":"Programa Operacional Tem\u00e1tico Factores de Competitividade","doi-asserted-by":"publisher","award":["POCI-01-0145-FEDER-30624"],"award-info":[{"award-number":["POCI-01-0145-FEDER-30624"]}],"id":[{"id":"10.13039\/501100011929","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>This work aims to optimize and assess the potential use of lipid nanoparticles, namely nanostructured lipid carriers (NLCs), as drug delivery systems of rifapentine (RPT) for the treatment of tuberculosis (TB). A Box\u2013Behnken design was used to increase drug encapsulation efficiency (EE) and loading capacity (LC) of RPT-loaded NLCs. The optimized nanoparticles were fully characterized, and their effect on cell viability was assessed. The quality-by-design approach allowed the optimization of RPT-loaded NLCs with improved EE and LC using the minimum of experiments. Analyses of variance were indicative of the validity of this model to optimize this nanodelivery system. The optimized NLCs had a mean diameter of 242 \u00b1 9 nm, polydispersity index &lt;0.2, and a highly negative zeta potential. EE values were higher than 80%, and differential scanning calorimetry analysis enabled the confirmation of the efficient encapsulation of RPT. Transmission electron microscopy analysis showed spherical nanoparticles, uniform in shape and diameter, with no visible aggregation. Stability studies indicated that NLCs were stable over time. No toxicity was observed in primary human macrophage viability for nanoparticles up to 1000 \u03bcg mL\u22121. Overall, the optimized NLCs are efficient carriers of RPT and should be considered for further testing as promising drug delivery systems to be used in TB treatment.<\/jats:p>","DOI":"10.3390\/pharmaceutics12010075","type":"journal-article","created":{"date-parts":[[2020,1,17]],"date-time":"2020-01-17T07:39:02Z","timestamp":1579246742000},"page":"75","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Optimization of Rifapentine-Loaded Lipid Nanoparticles Using a Quality-by-Design Strategy"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9421-0444","authenticated-orcid":false,"given":"Joana","family":"Magalh\u00e3es","sequence":"first","affiliation":[{"name":"LAQV, REQUIMTE, Departamento de Ci\u00eancias Qu\u00edmicas, Faculdade de Farm\u00e1cia, Universidade do Porto, 4050-313 Porto, Portugal"}]},{"given":"Luise","family":"L. Chaves","sequence":"additional","affiliation":[{"name":"LAQV, REQUIMTE, Departamento de Ci\u00eancias Qu\u00edmicas, Faculdade de Farm\u00e1cia, Universidade do Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9399-8169","authenticated-orcid":false,"given":"Alexandre","family":"C. Vieira","sequence":"additional","affiliation":[{"name":"LAQV, REQUIMTE, Departamento de Ci\u00eancias Qu\u00edmicas, Faculdade de Farm\u00e1cia, Universidade do Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8604-2978","authenticated-orcid":false,"given":"Susana","family":"G. Santos","sequence":"additional","affiliation":[{"name":"i3S-Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, INEB\u2014Instituto de Engenharia Biom\u00e9dica, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"ICBAS\u2014Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6931-1355","authenticated-orcid":false,"given":"Marina","family":"Pinheiro","sequence":"additional","affiliation":[{"name":"LAQV, REQUIMTE, Departamento de Ci\u00eancias Qu\u00edmicas, Faculdade de Farm\u00e1cia, Universidade do Porto, 4050-313 Porto, Portugal"}]},{"given":"Salette","family":"Reis","sequence":"additional","affiliation":[{"name":"LAQV, REQUIMTE, Departamento de Ci\u00eancias Qu\u00edmicas, Faculdade de Farm\u00e1cia, Universidade do Porto, 4050-313 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2020,1,17]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2019). 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