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For infectious diseases such as HIV, the CNS acts as a latent reservoir that is inadequately managed by systemic antiretrovirals (ARTs). ARTs thus cannot eradicate HIV, and given CNS infection, patients experience neurological deficits collectively referred to as \u201cneuroHIV\u201d. Herein, the development of bioinspired ionic liquid\u2010coated nanoparticles (IL\u2010NPs) for in situ hitchhiking on red blood cells (RBCs) is reported, which enables 48% brain delivery of intracarotid arterial\u2010 infused cargo. Moreover, IL choline trans\u20102\u2010hexenoate (CA2HA 1:2) demonstrates preferential accumulation in parenchymal microglia over endothelial cells post\u2010delivery. This study further demonstrates successful loading of abacavir (ABC), an ART that is challenging to encapsulate, into IL\u2010NPs, and verifies retention of antiviral efficacy in vitro. IL\u2010NPs are not cytotoxic to primary human peripheral blood mononuclear cells (PBMCs) and the CA2HA 1:2 coating itself confers notable anti\u2010viremic capacity. In addition, in vitro cell culture assays show markedly increased uptake of IL\u2010NPs into neural cells compared to bare PLGA nanoparticles. This work debuts bioinspired ionic liquids as promising nanoparticle coatings to assist CNS biodistribution and has the potential to revolutionize the delivery of cargos (i.e., drugs, viral vectors) through compartmental barriers such as the blood\u2010brain\u2010barrier (BBB).<\/jats:p>","DOI":"10.1002\/advs.202305484","type":"journal-article","created":{"date-parts":[[2024,4,4]],"date-time":"2024-04-04T03:49:57Z","timestamp":1712202597000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Ionic Liquid Coating\u2010Driven Nanoparticle Delivery to the Brain: Applications for NeuroHIV"],"prefix":"10.1002","volume":"11","author":[{"given":"Christine M.","family":"Hamadani","sequence":"first","affiliation":[{"name":"Department of Chemistry &amp; Biochemistry The University of Mississippi  University MS 38677 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fakhri","family":"Mahdi","sequence":"additional","affiliation":[{"name":"Department of BioMolecular Sciences The University of Mississippi  University MS 38677 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anya","family":"Merrell","sequence":"additional","affiliation":[{"name":"Department of Chemistry &amp; Biochemistry The University of Mississippi  University MS 38677 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack","family":"Flanders","sequence":"additional","affiliation":[{"name":"Department of Chemistry &amp; Biochemistry The University of Mississippi  University MS 38677 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruofan","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of BioMolecular Sciences The University of Mississippi  University MS 38677 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priyavrat","family":"Vashisth","sequence":"additional","affiliation":[{"name":"Department of Chemistry &amp; Biochemistry The University of Mississippi  University MS 38677 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaya S.","family":"Dasanayake","sequence":"additional","affiliation":[{"name":"Department of Chemistry &amp; Biochemistry The University of Mississippi  University MS 38677 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donovan S.","family":"Darlington","sequence":"additional","affiliation":[{"name":"Department of Chemistry &amp; Biochemistry The University of Mississippi  University MS 38677 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gagandeep","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Chemistry &amp; Biochemistry The University of Mississippi  University MS 38677 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mercedes C.","family":"Pride","sequence":"additional","affiliation":[{"name":"Department of Chemistry &amp; Biochemistry The University of Mississippi  University MS 38677 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wake G.","family":"Monroe","sequence":"additional","affiliation":[{"name":"Department of Chemistry &amp; Biochemistry The University of Mississippi  University MS 38677 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George R.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Department of Chemistry &amp; Biochemistry The University of Mississippi  University MS 38677 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alysha N.","family":"Hunter","sequence":"additional","affiliation":[{"name":"Department of Chemistry &amp; Biochemistry The University of Mississippi  University MS 38677 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregg","family":"Roman","sequence":"additional","affiliation":[{"name":"Department of BioMolecular Sciences The University of Mississippi  University MS 38677 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason J.","family":"Paris","sequence":"additional","affiliation":[{"name":"Department of BioMolecular Sciences The University of Mississippi  University MS 38677 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7919-2249","authenticated-orcid":false,"given":"Eden E. 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