{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T03:48:15Z","timestamp":1792813695928,"version":"4.5.0"},"reference-count":55,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,9,8]],"date-time":"2021-09-08T00:00:00Z","timestamp":1631059200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Ministry of Education, Culture, Sports, Science and Technology of Japan","award":["21K06656"],"award-info":[{"award-number":["21K06656"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>We previously designed ophthalmic formulations (nTRA) containing tranilast nanoparticles (Tra-NPs) with high uptake into ocular tissues. In this study, we used in situ gel (ISG) bases comprising combinations of pluronic F127 (F127) and methylcellulose (MC\/F127), pluronic F68 (F68\/F127), and Carbopol (Car\/F127), and we developed in situ gels incorporating Tra-NPs (Tra-NP-incorporated ISNGs) such as nTRA-F127, nTRA-MC\/F127, nTRA-F68\/F127, and nTRA-Car\/F127. Moreover, we demonstrated the therapeutic effect on conjunctival inflammation using lipopolysaccharide-induced rats. Each Tra-NP-incorporated ISNG was prepared by the bead mill method, the particle size was 40\u2013190 nm, and the tranilast release and diffusion from formulation were nTRA &gt; nTRA-F127 &gt; nTRA-F68\/F127 &gt; nTRA-Car\/F127 &gt; nTRA-MC\/F127. In the Tra-NP-incorporated ISNGs, the tranilast residence time in the lacrimal fluid, cornea, and conjunctiva was prolonged, although the Cmax was attenuated in comparison with nTRA. On the other hand, no significant difference in conjunctival inflammation between non- and nTRA-F127-instilled rats was found; however, the nTRA-F68\/F127, nTRA-Car\/F127, and nTRA-MC\/F127 (combination-ISG) attenuated the vessel leakage, nitric oxide, and tumor necrosis factor-\u03b1 expression. In particular, nTRA-F68\/F127 was significant in preventing the conjunctival inflammation. In conclusion, we found that the combination-ISG base prolonged the residence time of Tra-NPs; however, Tra-NP release from the formulation was attenuated, and the Tmax was delayed longer than that in nTRA. The balance of drug residence and diffusion in lacrimal fluid may be important in providing high ocular bioavailability in formulations containing solid nanoparticles.<\/jats:p>","DOI":"10.3390\/pharmaceutics13091425","type":"journal-article","created":{"date-parts":[[2021,9,8]],"date-time":"2021-09-08T10:12:03Z","timestamp":1631095923000},"page":"1425","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Balance of Drug Residence and Diffusion in Lacrimal Fluid Determine Ocular Bioavailability in In Situ Gels Incorporating Tranilast Nanoparticles"],"prefix":"10.3390","volume":"13","author":[{"given":"Misa","family":"Minami","sequence":"first","affiliation":[{"name":"Faculty of Pharmacy, Kindai University, 3-4-1 Kowakae, Higashi-Osaka, Osaka 577-8502, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroko","family":"Otake","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Kindai University, 3-4-1 Kowakae, Higashi-Osaka, Osaka 577-8502, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2226-1944","authenticated-orcid":false,"given":"Yosuke","family":"Nakazawa","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norio","family":"Okamoto","sequence":"additional","affiliation":[{"name":"Okamoto Eye Clinic, 5-11-12-312, Izumi-Cho, Suita, Osaka 564-0041, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9659-3204","authenticated-orcid":false,"given":"Naoki","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Center for Clinical Trial and Research Support, Research Promotion and Support Headquarters, Fujita Health University, 1-98 Dengakugakubo, Kutsukake, Toyoake 470-1192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6458-5330","authenticated-orcid":false,"given":"Hiroshi","family":"Sasaki","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Kahoku 920-0293, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriaki","family":"Nagai","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Kindai University, 3-4-1 Kowakae, Higashi-Osaka, Osaka 577-8502, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.1016\/j.addr.2005.07.005","article-title":"The use of mucoadhesive polymers in ocular drug delivery","volume":"57","author":"Ludwig","year":"2005","journal-title":"Adv. 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