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Res."],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>It was the aim of this study to design charge converting lipid nanoparticles (LNP) via a microfluidic mixing technique used for the preparation and coating of LNP. LNP consisting of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), cholesterol, N-(carbonyl-methoxypolyethyleneglycol-2000)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine (MPEG-2000-DSPE), and various cationic surfactants were prepared at diverging flow rate ratios (FRR) via microfluidic mixing. Utilizing a second chip in the microfluidic set-up, LNP were coated with polyoxyethylene (9) nonylphenol monophosphate ester (PNPP). LNP were examined for their stability in different physiologically relevant media as well as for hemolytic and cytotoxic effects. Finally, phosphate release and charge conversion of PNPP-coated LNP were evaluated after incubation with alkaline phosphatase and on Caco2-cells. LNP produced at an FRR of 5:1 exhibited a size between 80 and 150\u00a0nm and a positive zeta potential. Coating with PNPP within the second chip led to LNP exhibiting a negative zeta potential. After incubation with 1 U\/ml alkaline phosphatase for 4\u00a0h, zeta potential of the LNP containing 1,2-dioleoyloxy-3-trimethylammonium-propane chloride (DOTAP) as cationic component shifted from\u2009\u2212\u200935\u00a0mV to approximately\u2009+\u20095\u00a0mV. LNP prepared with other cationic surfactants remained slightly negative after enzymatic phosphate cleavage. Manufacturing of LNP containing PNPP and DOTAP via connection of two chips in a microfluidic instrument proves to show efficient change in zeta potential from negative to positive after incubation with alkaline phosphatase.<\/jats:p>\n                  <jats:p>\n                    <jats:bold>Graphical abstract<\/jats:bold>\n                  <\/jats:p>","DOI":"10.1007\/s13346-024-01538-5","type":"journal-article","created":{"date-parts":[[2024,2,21]],"date-time":"2024-02-21T09:02:34Z","timestamp":1708506154000},"page":"3173-3185","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Design of charge converting lipid nanoparticles via a microfluidic coating technique"],"prefix":"10.1007","volume":"14","author":[{"given":"Katrin","family":"Z\u00f6ller","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soheil","family":"Haddadzadegan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sera","family":"Lindner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florina","family":"Veider","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4187-8277","authenticated-orcid":false,"given":"Andreas","family":"Bernkop-Schn\u00fcrch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,2,21]]},"reference":[{"key":"1538_CR1","doi-asserted-by":"publisher","first-page":"3270","DOI":"10.1039\/D0BM00743A","volume":"8","author":"C Costa","year":"2020","unstructured":"Costa C, Liu Z, Martins JP, Correia A, Figueiredo P, Rahikkala A, Li W, Seitsonen J, Ruokolainen J, Hirvonen SP, Aguiar-Ricardo A, Corvo ML, Santos HA. 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