{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:10:18Z","timestamp":1787026218835,"version":"build-2736575974"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,3,10]],"date-time":"2023-03-10T00:00:00Z","timestamp":1678406400000},"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. Bioeng. Biotechnol."],"abstract":"<jats:p>\n                    The permeability of the Biopharmaceutics Classification System (BCS) class III drugs are low, and their oral bioavailability needs to be improved. In this study, we attempted to design oral formulations containing famotidine (FAM) nanoparticles to overcome the limitations of BCS class III drugs. Dispersions containing FAM nanoparticles with a particle size of approximately 50\u2013220\u00a0nm were produced by the bead-milling treatment. Moreover, we succeeded in preparing an orally disintegrating tablet containing FAM nanoparticles using the dispersions described above, additives (D-mannitol, polyvinylpyrrolidone, and gum arabic), and freeze-dry treatment (FAM-NP tablet). The FAM-NP tablet was disaggregated 3.5\u00a0s after addition to purified water, and the FAM particles in the redispersion of the FAM-NP tablet stored for 3\u00a0months were nano-sized (141 \u00b1 6.6\u00a0nm). The\n                    <jats:italic>ex-vivo<\/jats:italic>\n                    intestinal penetration and\n                    <jats:italic>in vivo<\/jats:italic>\n                    absorption of FAM in rats applied with the FAM-NP tablet were significantly higher than those in rats applied with the FAM tablet containing microparticles. In addition, enhanced intestinal penetration of the FAM-NP tablet was attenuated by an inhibitor of clathrin-mediated endocytosis. In conclusion, the orally disintegrating tablet containing FAM nanoparticles improved low mucosal permeability and low oral bioavailability and overcame these issues of BCS class III drugs as oral formulations.\n                  <\/jats:p>","DOI":"10.3389\/fbioe.2023.1167291","type":"journal-article","created":{"date-parts":[[2023,3,10]],"date-time":"2023-03-10T00:13:00Z","timestamp":1678407180000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Orally disintegrating tablets containing famotidine nanoparticles provide high intestinal absorbability via the energy-dependent endocytosis pathway"],"prefix":"10.3389","volume":"11","author":[{"given":"Noriaki","family":"Nagai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumihiko","family":"Ogata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reita","family":"Kadowaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saori","family":"Deguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroko","family":"Otake","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yosuke","family":"Nakazawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayumi","family":"Nagata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Sasaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naohito","family":"Kawasaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,3,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1688","DOI":"10.1016\/j.addr.2006.09.017","article-title":"Freeze-drying of nanoparticles: Formulation, process and storage considerations","volume":"58","author":"Abdelwahed","year":"2006","journal-title":"Adv. Drug Deliv. Rev."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1404","DOI":"10.3390\/pharmaceutics13091404","article-title":"Nanocrystalline suspensions of irbesartan enhance oral bioavailability by improving drug solubility and leading endocytosis uptake into the intestine","volume":"13","author":"Deguchi","year":"2021","journal-title":"Pharmaceutics"},{"key":"B3","doi-asserted-by":"publisher","first-page":"993","DOI":"10.1016\/j.ejpb.2008.02.017","article-title":"Enhancement of famotidine dissolution rate through liquisolid tablets formulation: In vitro and in vivo evaluation","volume":"69","author":"Fahmy","year":"2008","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"B4","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/0378-5173(90)90282-9","article-title":"Improvement of the in vitro dissolution characteristics of famotidine by inclusion in \u03b2-cyclodextrin","volume":"58","author":"Hassan","year":"1990","journal-title":"Int. J. Pharm."},{"key":"B5","doi-asserted-by":"publisher","first-page":"5298","DOI":"10.1038\/s41598-018-23262-0","article-title":"Cold atmospheric plasma induces ATP-dependent endocytosis of nanoparticles and synergistic U373MG cancer cell death","volume":"8","author":"He","year":"2018","journal-title":"Sci. Rep."},{"key":"B6","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1053\/bega.2001.0184","article-title":"Pharmacological and pharmacodynamic essentials of H(2)-receptor antagonists and proton pump inhibitors for the practising physician","volume":"15","author":"Huang","year":"2001","journal-title":"Best. Pract. Res. Clin. Gastroenterol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1411","DOI":"10.1038\/mt.2009.121","article-title":"Fluid phase endocytosis contributes to transfection of DNA by PEI-25","volume":"17","author":"Hufnagel","year":"2009","journal-title":"Mol. Ther."},{"key":"B8","doi-asserted-by":"publisher","first-page":"452051","DOI":"10.1155\/2014\/452051","article-title":"In vitro intestinal permeability studies and pharmacokinetic evaluation of famotidine microemulsion for oral delivery","volume":"2014","author":"Jha","year":"2014","journal-title":"Int. Sch. Res. Not."},{"key":"B9","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.xphs.2016.09.014","article-title":"Pharmaceutical amorphous nanoparticles","volume":"106","author":"Jog","year":"2017","journal-title":"J. Pharm. Sci."},{"key":"B10","doi-asserted-by":"publisher","first-page":"3064","DOI":"10.1208\/s12249-017-0780-7","article-title":"Optimized mucoadhesive coated niosomes as a sustained oral delivery system of famotidine","volume":"18","author":"Khalifa","year":"2017","journal-title":"AAPS PharmSciTech"},{"key":"B11","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/978-1-4614-0554-2_13","article-title":"Nanosuspensions","volume-title":"Long acting injections and implants","author":"Kumar","year":"2012"},{"key":"B12","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1016\/j.ijpharm.2014.03.021","article-title":"Wet milling induced physical and chemical instabilities of naproxen nano-crystalline suspensions","volume":"466","author":"Kumar","year":"2014","journal-title":"Int. J. Pharm."},{"key":"B13","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.jconrel.2014.06.059","article-title":"Nano-amorphous spray dried powder to improve oral bioavailability of itraconazole","volume":"192","author":"Kumar","year":"2014","journal-title":"J. Control. Release"},{"key":"B14","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1016\/j.ijpharm.2014.09.008","article-title":"Controlled delivery of carvedilol nanosuspension from osmotic pump capsule: In vitro and in vivo evaluation","volume":"475","author":"Liu","year":"2014","journal-title":"Int. J. Pharm."},{"key":"B15","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/0002-9343(86)90598-x","article-title":"Efficacy and safety of famotidine in the management of benign gastric ulcers","volume":"81","author":"Lyon","year":"1986","journal-title":"Am. J. Med."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ijpharm.2010.06.018","article-title":"Evaluation of carboxymethyl-beta-cyclodextrin with acid function: Improvement of chemical stability, oral bioavailability and bitter taste of famotidine","volume":"397","author":"Mady","year":"2010","journal-title":"Int. J. Pharm."},{"key":"B17","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1016\/j.bbamem.2011.11.020","article-title":"The role of endocytosis on the uptake kinetics of luciferin-conjugated cell-penetrating peptides","volume":"1818","author":"M\u00e4ger","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1449","DOI":"10.1016\/S0140-6736(09)60938-7","article-title":"Peptic ulcer disease","volume":"374","author":"Malfertheiner","year":"2009","journal-title":"Lancet"},{"key":"B19","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1134\/S0012496614060052","article-title":"The effect of dynasore, a blocker of dynamin-dependent endocytosis, on spontaneous quantal and non-quantal release of acetylcholine in murine neuromuscular junctions","volume":"459","author":"Malomouzh","year":"2014","journal-title":"Dokl. Biol. Sci."},{"key":"B20","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/j.fluid.2010.09.029","article-title":"Determination and correlation of solubilities of famotidine in water + co-solvent mixed solvents","volume":"302","author":"Matsuda","year":"2011","journal-title":"Fluid Phase Equilib."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1622","DOI":"10.1111\/j.2042-7158.2010.01107.x","article-title":"New perspectives on lipid and surfactant based drug delivery systems for oral delivery of poorly soluble drugs","volume":"62","author":"M\u00fcllertz","year":"2010","journal-title":"J. Pharm. Pharmacol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.tox.2014.02.012","article-title":"A nanoparticle formulation reduces the corneal toxicity of indomethacin eye drops and enhances its corneal permeability","volume":"319","author":"Nagai","year":"2014","journal-title":"Toxicology"},{"key":"B23","doi-asserted-by":"publisher","first-page":"7921","DOI":"10.2147\/IJN.S225496","article-title":"<p&gt;Drug delivery system based on minoxidil nanoparticles promotes hair growth in C57bl\/6 mice<\/p&gt;","volume":"14","author":"Nagai","year":"","journal-title":"Int. J. Nanomedicine"},{"key":"B24","doi-asserted-by":"publisher","first-page":"387","DOI":"10.3390\/pharmaceutics14020387","article-title":"Oral formulation based on irbesartan nanocrystals improve drug solubility, absorbability, and efficacy","volume":"14","author":"Nagai","year":"2022","journal-title":"Pharmaceutics"},{"key":"B25","doi-asserted-by":"publisher","first-page":"313","DOI":"10.3390\/pharmaceutics12040313","article-title":"Oral administration system based on meloxicam nanocrystals: Decreased dose due to high bioavailability attenuates risk of gastrointestinal side effects","volume":"12","author":"Nagai","year":"2020","journal-title":"Pharmaceutics"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1213","DOI":"10.2147\/IJN.S196681","article-title":"<p&gt;Energy-dependent endocytosis is responsible for drug transcorneal penetration following the instillation of ophthalmic formulations containing indomethacin nanoparticles&lt;\/p&gt;","volume":"14","author":"Nagai","year":"","journal-title":"Int. J. Nanomedicine"},{"key":"B27","doi-asserted-by":"publisher","first-page":"5343","DOI":"10.2147\/IJN.S317046","article-title":"Fixed-combination eye drops based on fluorometholone nanoparticles and bromfenac\/levofloxacin solution improve drug corneal penetration","volume":"16","author":"Otake","year":"2021","journal-title":"Int. J. Nanomedicine"},{"key":"B28","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1590\/S1516-89132013000200007","article-title":"Design and evaluation of famotidine mucoadhesive nanoparticles for aspirin induced ulcer treatment","volume":"56","author":"Patel","year":"2013","journal-title":"Braz. Arch. Biol. Technol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"189","DOI":"10.3923\/jpt.2011.189.195","article-title":"Evaluation of gastric and duodenal antiulcer activity of famotidine formulation in experimental animals","volume":"6","author":"Ramchandran","year":"2011","journal-title":"J. Pharmacol. Toxicol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1080\/10717544.2019.1704940","article-title":"Mechanisms of increased bioavailability through amorphous solid dispersions: A review","volume":"27","author":"Schittny","year":"2020","journal-title":"Drug Deliv."},{"key":"B31","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1124\/pr.112.005660","article-title":"Strategies to address low drug solubility in discovery and development","volume":"65","author":"Williams","year":"2013","journal-title":"Pharmacol. Rev."}],"container-title":["Frontiers in Bioengineering and Biotechnology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fbioe.2023.1167291\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,10]],"date-time":"2023-03-10T00:13:03Z","timestamp":1678407183000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fbioe.2023.1167291\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,10]]},"references-count":31,"alternative-id":["10.3389\/fbioe.2023.1167291"],"URL":"https:\/\/doi.org\/10.3389\/fbioe.2023.1167291","relation":{},"ISSN":["2296-4185"],"issn-type":[{"value":"2296-4185","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,10]]},"article-number":"1167291"}}