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This underscores the urgent need for novel therapeutic strategies, such as targeting host factors, which may reduce the likelihood of resistance. Here, we evaluated inhibitors of G protein\u2010coupled receptor kinases (GRKs; paroxetine, CMPD101) and protein kinase C (PKC; G\u00f66983, bisindolylmaleimide\u2010I (BIM\u2010I)) for anti\u2010IAV activity. GRK inhibition showed no significant effect, whereas PKC inhibition, particularly with BIM\u2010I, significantly reduced infection. To overcome BIM\u2010I's poor solubility and concentration\u2010dependent cytotoxicity, it is encapsulated into poly(lactic\u2010\n                    <jats:italic>co<\/jats:italic>\n                    \u2010glycolic acid) (PLGA)\u2010based nanoparticles. To enhance nanoparticle performance, stealth polymers like polyethylene glycol (PEG) are commonly incorporated. However, concerns about PEG immunogenicity have increased interest in alternatives like poly(2\u2010ethyl\u20102\u2010oxazoline) (PEtOx). We formulated BIM\u2010I\u2010loaded nanoparticles containing either PEG or PEtOx and characterized them for their physicochemical properties, cytotoxicity, antiviral efficacy, and cellular uptake. Encapsulation improved the cellular tolerability of BIM\u2010I while preserving its antiviral activity. Confocal microscopy confirmed efficient uptake of all formulations, particularly PEGylated and PEtOxylated nanoparticles. These findings highlight nanoparticle\u2010mediated delivery of BIM\u2010I as a promising host\u2010directed antiviral strategy against IAV and support PEtOx as a viable PEG alternative in nanomedicine.\n                  <\/jats:p>","DOI":"10.1002\/adhm.202504060","type":"journal-article","created":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T08:56:07Z","timestamp":1763801767000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Evaluating the Antiviral Efficacy of Encapsulated PKC Inhibitor BIM\u2010I against influenza A Virus Infection"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-3956-6059","authenticated-orcid":false,"given":"Laura","family":"Klement","sequence":"first","affiliation":[{"name":"Institute of Molecular Cell Biology Center for Molecular Biomedicine (CMB) University Hospital Jena Friedrich Schiller University Jena  Jena 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