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However, dose\u2010limiting toxicities including cytokine storm and hypotension has limited its use in the clinic as a cancer therapy. We propose that polymeric microparticle (MP)\u2010based delivery of IL\u20101\u03b1 will suppress the acute pro\u2010inflammatory side effects by allowing for slow and controlled release of IL\u20101\u03b1 systemically, while simultaneously triggering an anti\u2010tumor immune response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Polyanhydride copolymers composed of 1,6\u2010bis\u2010(p\u2010carboxyphenoxy)\u2010hexane:sebacic 20:80 (CPH:SA 20:80) was utilized to fabricate MPs. Recombinant IL\u20101\u03b1 (rIL\u20101\u03b1) was encapsulated into CPH:SA 20:80 MPs (IL\u20101\u03b1\u2010MPs) and the MPs were characterized by size, charge, loading efficiency, and in\u2010vitro release and activity of IL\u20101\u03b1. IL\u20101\u03b1\u2010MPs were injected intraperitonially into head and neck squamous cell carcinoma (HNSCC)\u2010bearing C57Bl\/6 mice and monitored for changes in weight, tumor growth, circulating cytokines\/chemokines, hepatic and kidney enzymes, blood pressure, heart rate, and tumor\u2010infiltrating immune cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>CPH:SA IL\u20101\u03b1\u2010MPs demonstrated sustained release kinetics of IL\u20101\u03b1 (100% protein released over 8\u201310\u2009days) accompanied by minimal weight loss and systemic inflammation compared to rIL\u20101\u03b1\u2010treated mice. Blood pressure measured by radiotelemetry in conscious mice demonstrates that rIL\u20101\u03b1\u2010induced hypotension was prevented in IL\u20101\u03b1\u2010MP\u2010treated mice. Liver and kidney enzymes were within normal range for all control and cytokine\u2010treated mice. Both rIL\u20101\u03b1 and IL\u20101\u03b1\u2010MP\u2010treated mice showed similar delays in tumor growth and similar increases in tumor\u2010infiltrating CD3+ T cells, macrophages, and dendritic cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>CPH:SA\u2010based IL\u20101\u03b1\u2010MPs generated a slow and sustained systemic release of IL\u20101\u03b1 resulting in reduced weight loss, systemic inflammation, and hypotension accompanied by an adequate anti\u2010tumor immune response in HNSCC\u2010tumor bearing mice. Therefore, MPs based on CPH:SA formulations may be promising as delivery vehicles for IL\u20101\u03b1 to achieve safe, effective, and durable antitumor responses for HNSCC patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/btm2.10465","type":"journal-article","created":{"date-parts":[[2022,12,7]],"date-time":"2022-12-07T17:11:20Z","timestamp":1670433080000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Characterization of\n                    <scp>CPH<\/scp>\n                    :\n                    <scp>SA<\/scp>\n                    microparticle\u2010based delivery of interleukin\u20101 alpha for cancer immunotherapy"],"prefix":"10.1002","volume":"8","author":[{"given":"M. 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