{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T15:07:39Z","timestamp":1791472059297,"version":"4.3.4"},"reference-count":47,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2020,1,24]],"date-time":"2020-01-24T00:00:00Z","timestamp":1579824000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01NS111292"],"award-info":[{"award-number":["R01NS111292"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["W81XWH-14-1-0311"],"award-info":[{"award-number":["W81XWH-14-1-0311"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["DGE-1311230"],"award-info":[{"award-number":["DGE-1311230"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008222","name":"Ben and Catherine Ivy Foundation","doi-asserted-by":"publisher","award":["N.A."],"award-info":[{"award-number":["N.A."]}],"id":[{"id":"10.13039\/100008222","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013014","name":"Barrow Neurological Institute","doi-asserted-by":"publisher","award":["N.A."],"award-info":[{"award-number":["N.A."]}],"id":[{"id":"10.13039\/100013014","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Alternative routes of administration are one approach that could be used to bypass the blood\u2013brain barrier (BBB) for effective drug delivery to the central nervous system (CNS). Here, we focused on intranasal delivery of polymer nanoparticles. We hypothesized that surface modification of poly(lactic-co-glycolic acid) (PLGA) nanoparticles with rabies virus glycoprotein (RVG29) would increase residence time and exposure of encapsulated payload to the CNS compared to non-targeted nanoparticles. Delivery kinetics and biodistribution were analyzed by administering nanoparticles loaded with the carbocyanine dye 1,1\u2032-Dioctadecyl-3,3,3\u2032,3\u2032-Tetramethylindotricarbocyanine Iodide (DiR) to healthy mice. Intranasal administration yielded minimal exposure of nanoparticle payload to most peripheral organs and rapid, effective delivery to whole brain. Regional analysis of payload delivery within the CNS revealed higher delivery to tissues closest to the trigeminal nerve, including the olfactory bulb, striatum, midbrain, brainstem, and cervical spinal cord. RVG29 surface modifications presented modest targeting benefits to the striatum, midbrain, and brainstem 2 h after administration, although targeting was not observed 30 min or 6 h after administration. Payload delivery to the trigeminal nerve was 3.5\u00d7 higher for targeted nanoparticles compared to control nanoparticles 2 h after nanoparticle administration. These data support a nose-to-brain mechanism of drug delivery that closely implicates the trigeminal nerve for payload delivery from nanoparticles via transport of intact nanoparticles and eventual diffusion of payload. Olfactory and CSF routes are also observed to play a role. These data advance the utility of targeted nanoparticles for nose-to-brain drug delivery of lipophilic payloads and provide mechanistic insight to engineer effective delivery vectors to treat disease in the CNS.<\/jats:p>","DOI":"10.3390\/pharmaceutics12020093","type":"journal-article","created":{"date-parts":[[2020,1,24]],"date-time":"2020-01-24T11:01:00Z","timestamp":1579863660000},"page":"93","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":66,"title":["Targeting Small Molecule Delivery to the Brain and Spinal Cord via Intranasal Administration of Rabies Virus Glycoprotein (RVG29)-Modified PLGA Nanoparticles"],"prefix":"10.3390","volume":"12","author":[{"given":"Eugene P.","family":"Chung","sequence":"first","affiliation":[{"name":"Barrow Brain Tumor Research Center, Barrow Neurological Institute, Phoenix, AZ 85013, USA"},{"name":"School of Life Sciences, Arizona State University, Tempe, AZ 85281, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer D.","family":"Cotter","sequence":"additional","affiliation":[{"name":"Vivian L. Smith Department of Neurosurgery, McGovern Medical School, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alesia V.","family":"Prakapenka","sequence":"additional","affiliation":[{"name":"Barrow Brain Tumor Research Center, Barrow Neurological Institute, Phoenix, AZ 85013, USA"},{"name":"School of Life Sciences, Arizona State University, Tempe, AZ 85281, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9009-9937","authenticated-orcid":false,"given":"Rebecca L.","family":"Cook","sequence":"additional","affiliation":[{"name":"Barrow Brain Tumor Research Center, Barrow Neurological Institute, Phoenix, AZ 85013, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle M.","family":"DiPerna","sequence":"additional","affiliation":[{"name":"Barrow Brain Tumor Research Center, Barrow Neurological Institute, Phoenix, AZ 85013, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachael W.","family":"Sirianni","sequence":"additional","affiliation":[{"name":"Barrow Brain Tumor Research Center, Barrow Neurological Institute, Phoenix, AZ 85013, USA"},{"name":"School of Life Sciences, Arizona State University, Tempe, AZ 85281, USA"},{"name":"Vivian L. Smith Department of Neurosurgery, McGovern Medical School, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,1,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"35","DOI":"10.3233\/JAD-1998-1102","article-title":"Delivery of nerve growth factor to the brain via the olfactory pathway","volume":"1","author":"Chen","year":"1998","journal-title":"J. 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