{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T18:30:05Z","timestamp":1790188205472,"version":"4.1.0"},"reference-count":32,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,5,30]],"date-time":"2021-05-30T00:00:00Z","timestamp":1622332800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Polymers"],"abstract":"<jats:p>Cisplatin (cis-diamminedichloroplatinum (II); CDDP) is a key chemotherapeutic agent but causes renal damage and other off-target effects. Here, we describe the pharmacological and biochemical characteristics of a novel formulation of CDDP complexed with \u03b3-polyglutamic acid (\u03b3-PGA) and chitosan (CS), \u03b3-PGA\/CDDP-CS, developed by complexing CDDP with \u03b3-PGA, then adding CS (15 kDa; 10 mol%\/\u03b3-PGA). We analyzed tumor cytotoxicity in vitro, as well as blood kinetics, acute toxicity, and antitumor efficacy in vivo in BALB\/cAJcl mice. \u03b3-PGA\/CDDP-CS showed pH-dependent release in vitro over 12 days (9.1% CDDP released at pH 7.4; 49.9% at pH 5.5). It showed in vitro cytotoxicity in a dose-dependent manner similar to that of uncomplexed CDDP. In a mesothelioma-bearing mouse model, a 15 mg\/kg dose of CDDP inhibited tumor growth regardless of the type of formulation, complexed or uncomplexed; however, all mice in the uncomplexed CDDP group died within 13 days. \u03b3-PGA\/CDDP-CS was as effective as free CDDP in vivo but much less toxic.<\/jats:p>","DOI":"10.3390\/polym13111803","type":"journal-article","created":{"date-parts":[[2021,5,31]],"date-time":"2021-05-31T03:45:29Z","timestamp":1622432729000},"page":"1803","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A Novel Formulation of Cisplatin with \u03b3-Polyglutamic Acid and Chitosan Reduces Its Adverse Renal Effects: An In Vitro and In Vivo Animal Study"],"prefix":"10.3390","volume":"13","author":[{"given":"Masao","family":"Sasai","sequence":"first","affiliation":[{"name":"Division of Translational Research, Osaka University Hospital, Suita 565-0871, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuma","family":"Sakura","sequence":"additional","affiliation":[{"name":"Division of Translational Research, Osaka University Hospital, Suita 565-0871, Japan"},{"name":"Respiratory Center, Osaka University Hospital, Suita 565-0871, Japan"},{"name":"Department of Surgery, Graduate School of Medicine, Osaka University, Suita 565-0871, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Matsuda","sequence":"additional","affiliation":[{"name":"Department of Applied Chemistry, Graduate School of Engineering, Osaka University, Suita 565-0871, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8587-2507","authenticated-orcid":false,"given":"Hiroshi","family":"Uyama","sequence":"additional","affiliation":[{"name":"Department of Applied Chemistry, Graduate School of Engineering, Osaka University, Suita 565-0871, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1002\/jat.1081","article-title":"Role of ERK activation in cisplatin-induced apoptosis in OK renal epithelial cells","volume":"25","author":"Kim","year":"2005","journal-title":"J. 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