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Biodegradable, disulfide\u2010crosslinked synthetic nanogels are a promising platform for the delivery of therapeutic molecules, but their biodistribution and clearance profiles remain underexplored compared to other solid nanoparticles. In this study, we investigated the safety, pharmacokinetics, tissue, and cellular distribution profiles of poly(acrylamide\u2010co\u2010methacrylic acid) (P(AAm\u2010co\u2010MAA)) nanogels following a single intravenous or intraperitoneal injection. The nanogels exhibited rapid clearance from plasma, followed by early distribution primarily to the kidneys, liver, and small intestine. Within the liver, the nanogels showed preferential uptake by endothelial cells and resident macrophages. We further revealed organ\u2010specific differences in nanogel retention and clearance, with highly perfused organs demonstrating parallel clearance behavior with plasma, while organs such as the kidneys and small intestine served as sites of longer nanogel retention. Single injections of P(AAm\u2010co\u2010MAA) nanogel suspension did not induce any systemic innate immune activation nor organ\u2010specific toxicity, demonstrating a promising safety profile. These findings provide new insights into the in\u00a0vivo behavior of redox\u2010responsive nanogels and provide a framework for their rational design and clinical translation.<\/jats:p>","DOI":"10.1002\/jbm.a.70072","type":"journal-article","created":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T14:16:38Z","timestamp":1774275398000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Safety, Distribution, and Pharmacokinetics of Biodegradable P(\n                    <scp>AAm<\/scp>\n                    \u2010co\u2010\n                    <scp>MAA<\/scp>\n                    ) Nanogels Following Systemic Administration in Mice"],"prefix":"10.1002","volume":"114","author":[{"given":"Rana","family":"Ajeeb","sequence":"first","affiliation":[{"name":"Stephenson School of Biomedical Engineering The University of Oklahoma  Norman Oklahoma USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harsh","family":"Joshi","sequence":"additional","affiliation":[{"name":"Stephenson School of Biomedical Engineering The University of Oklahoma  Norman Oklahoma USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mojtaba","family":"Ghanbari Mehrabani","sequence":"additional","affiliation":[{"name":"Stephenson School of Biomedical Engineering The University of Oklahoma  Norman Oklahoma USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Pierce","sequence":"additional","affiliation":[{"name":"Stephenson School of Biomedical Engineering The University of Oklahoma  Norman Oklahoma USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7244-3041","authenticated-orcid":false,"given":"John R.","family":"Clegg","sequence":"additional","affiliation":[{"name":"Stephenson School of Biomedical Engineering The University of Oklahoma  Norman Oklahoma USA"},{"name":"Department of Neurosurgery The University of Oklahoma Health Campus  Oklahoma City Oklahoma USA"},{"name":"Stephenson Cancer Center The University of Oklahoma Health Campus  Oklahoma City Oklahoma USA"},{"name":"Harold Hamm Diabetes Center The University of Oklahoma Health Campus  Oklahoma City Oklahoma USA"},{"name":"Institute for Biomedical Engineering, Science and Technology (IBEST) The University of Oklahoma  Norman Oklahoma USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,23]]},"reference":[{"key":"e_1_2_10_2_1","first-page":"5729","article-title":"Closing the Gap: Accelerating the Translational Process in Nanomedicine by Proposing Standardized Characterization Techniques","volume":"9","author":"Khorasani A. 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