{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T15:21:22Z","timestamp":1783351282451,"version":"3.54.6"},"reference-count":37,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2021,10,25]],"date-time":"2021-10-25T00:00:00Z","timestamp":1635120000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bladder Cancer"],"published-print":{"date-parts":[[2021,12,13]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Intravesical administration of interleukin 12 (IL-12) co-formulated with the biopolymer, chitosan (CS\/IL-12), has demonstrated remarkable antitumor activity against preclinical models of bladder cancer. However, given historical concerns regarding severe toxicities associated with systemic IL-12 administration in clinical trials, it is important to evaluate the safety of intravesical CS\/IL-12 prior to clinical translation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>OBJECTIVE:<\/jats:title>\n                    <jats:p>To evaluate the pharmacokinetics as well as the local and systemic toxicities of intravesical CS\/IL-12 immunotherapy in laboratory mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>Local inflammatory responses in mouse bladders treated with intravesical IL-12 or CS\/IL-12 were assessed via histopathology. Serum cytokine levels following intravesical and subcutaneous (s.c.) administrations of IL-12 or CS\/IL-12 in laboratory mice were compared. Systemic toxicities were evaluated via body weight and liver enzyme levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>Intravesical IL-12 and CS\/IL-12 treatments did not induce significant local or systemic toxicity. IL-12 dissemination and exposure from intravesical administration was significantly lower compared to s.c. injections. Weekly intravesical CS\/IL-12 treatments were well-tolerated and did not result in blunted immune responses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>Intravesical CS\/IL-12 is safe and well-tolerated in mice. In particular, the lack of cystitis and acute inflammation justifies continued investigation of intravesical CS\/IL-12 immunotherapy in larger animals and patients with bladder cancer.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3233\/blc-211542","type":"journal-article","created":{"date-parts":[[2021,10,26]],"date-time":"2021-10-26T11:47:32Z","timestamp":1635248852000},"page":"427-437","source":"Crossref","is-referenced-by-count":4,"title":["Safety and Pharmacokinetics of Intravesical Chitosan\/Interleukin-12 Immunotherapy in Murine Bladders"],"prefix":"10.1177","volume":"7","author":[{"given":"Khue G.","family":"Nguyen","sequence":"first","affiliation":[{"name":"Joint Department of Biomedical Engineering, North Carolina State University and University of North Carolina-Chapel Hill, Raleigh, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ethan S.","family":"Wagner","sequence":"additional","affiliation":[{"name":"Joint Department of Biomedical Engineering, North Carolina State University and University of North Carolina-Chapel Hill, Raleigh, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maura R.","family":"Vrabel","sequence":"additional","affiliation":[{"name":"Joint Department of Biomedical Engineering, North Carolina State University and University of North Carolina-Chapel Hill, Raleigh, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siena M.","family":"Mantooth","sequence":"additional","affiliation":[{"name":"Joint Department of Biomedical Engineering, North Carolina State University and University of North Carolina-Chapel Hill, Raleigh, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle M.","family":"Meritet","sequence":"additional","affiliation":[{"name":"Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Zaharoff","sequence":"additional","affiliation":[{"name":"Joint Department of Biomedical Engineering, North Carolina State University and University of North Carolina-Chapel Hill, Raleigh, NC, 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