{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T19:27:44Z","timestamp":1792956464441,"version":"4.5.0"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2022,8,9]],"date-time":"2022-08-09T00:00:00Z","timestamp":1660003200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100001279","name":"Orthopaedic Research and Education Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001279","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>A local anesthetic that provides analgesia lasting at least three days could significantly improve postoperative pain management. This study evaluated the analgesic efficacy and safety of an extended-release formulation of bupivacaine based on the injectable hydrogel carrier poly(N-isopropylacrylamide-co-dimethylbutyrolactone acrylamide-co-Jeffamine M-1000 acrylamide) (PNDJ).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>The efficacy of PNDJ containing 4% bupivacaine (SBG004) given by peri-incisional subcutaneous injection (SBG004 SC) or wound filling instillation (SBG004 WF) was evaluated compared to saline, liposomal bupivacaine, bupivacaine collagen sponge, bupivacaine-meloxicam polyorthoester, and bupivacaine HCl in a porcine skin and muscle incision model. Mechanical allodynia was assessed by withdrawal from application of von Frey filaments, and local tolerance was evaluated by histology. Bupivacaine pharmacokinetics for SBG004 SC were measured in rabbits (16.5\u2009mg bupivacaine\/kg).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Animals demonstrated less mechanical allodynia at incisions receiving SBG004 SC for up to 96\u2009hours postoperatively. Incisions treated with SBG004 SC tolerated more force without a withdrawal indicative of pain compared to saline for 96\u2009hours, and compared to SBG004 WF and all active controls at 24, 48, and 72\u2009hours except bupivacaine-meloxicam polyorthoester at 72\u2009hours. By 49\u2009days, SBG004 was histologically absent and was replaced with granulation tissue infiltrated with immune cells in some areas. In rabbits, Cmax was 41.6\u2009\u00b1\u20099.7\u2009ng\/mL with t1\/2 82.0\u2009\u00b1\u200935.8\u2009hours (mean\u2009\u00b1\u2009SD).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Peri-incisional SBG004 SC provided extended release of bupivacaine sufficient to reduce sensation of incisional pain for 96\u2009hours, in vivo bupivacaine delivery for at least 7\u2009days, and a favorable local and systemic toxicity profile.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/pm\/pnac119","type":"journal-article","created":{"date-parts":[[2022,8,9]],"date-time":"2022-08-09T19:59:56Z","timestamp":1660075196000},"page":"113-121","source":"Crossref","is-referenced-by-count":13,"title":["Extended Release of Bupivacaine from Temperature-responsive Hydrogels Provides Multi-day Analgesia for Postoperative Pain"],"prefix":"10.1093","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0817-0966","authenticated-orcid":false,"given":"John M","family":"Heffernan","sequence":"first","affiliation":[{"name":"Sonoran Biosciences , Tempe, Arizona, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex C","family":"McLaren","sequence":"additional","affiliation":[{"name":"Sonoran Biosciences , Tempe, Arizona, USA"},{"name":"Department of Orthopaedic Surgery, University of Arizona College of Medicine , Phoenix, Arizona, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher M","family":"Glass","sequence":"additional","affiliation":[{"name":"School of Biological & Health Systems Engineering, Arizona State University , Tempe, Arizona, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek J","family":"Overstreet","sequence":"additional","affiliation":[{"name":"Sonoran Biosciences , Tempe, Arizona, USA"},{"name":"School of 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