Targeting Small Molecule Delivery to the Brain and Spinal Cord via Intranasal Administration of Rabies Virus Glycoprotein (RVG29)-Modified PLGA Nanoparticles
Alternative routes of administration are one approach that could be used to bypass the blood−brain 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 p...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-01-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/12/2/93 |
| _version_ | 1818000984911118336 |
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| author | Eugene P. Chung Jennifer D. Cotter Alesia V. Prakapenka Rebecca L. Cook Danielle M. DiPerna Rachael W. Sirianni |
| author_facet | Eugene P. Chung Jennifer D. Cotter Alesia V. Prakapenka Rebecca L. Cook Danielle M. DiPerna Rachael W. Sirianni |
| author_sort | Eugene P. Chung |
| collection | DOAJ |
| description | Alternative routes of administration are one approach that could be used to bypass the blood−brain 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-<i>co</i>-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′-Dioctadecyl-3,3,3′,3′-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× 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. |
| first_indexed | 2024-04-14T03:28:21Z |
| format | Article |
| id | doaj.art-af82be53c03a49528291e5a397890d35 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-04-14T03:28:21Z |
| publishDate | 2020-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-af82be53c03a49528291e5a397890d352022-12-22T02:15:04ZengMDPI AGPharmaceutics1999-49232020-01-011229310.3390/pharmaceutics12020093pharmaceutics12020093Targeting Small Molecule Delivery to the Brain and Spinal Cord via Intranasal Administration of Rabies Virus Glycoprotein (RVG29)-Modified PLGA NanoparticlesEugene P. Chung0Jennifer D. Cotter1Alesia V. Prakapenka2Rebecca L. Cook3Danielle M. DiPerna4Rachael W. Sirianni5Barrow Brain Tumor Research Center, Barrow Neurological Institute, Phoenix, AZ 85013, USAVivian L. Smith Department of Neurosurgery, McGovern Medical School, Houston, TX 77030, USABarrow Brain Tumor Research Center, Barrow Neurological Institute, Phoenix, AZ 85013, USABarrow Brain Tumor Research Center, Barrow Neurological Institute, Phoenix, AZ 85013, USABarrow Brain Tumor Research Center, Barrow Neurological Institute, Phoenix, AZ 85013, USABarrow Brain Tumor Research Center, Barrow Neurological Institute, Phoenix, AZ 85013, USAAlternative routes of administration are one approach that could be used to bypass the blood−brain 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-<i>co</i>-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′-Dioctadecyl-3,3,3′,3′-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× 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.https://www.mdpi.com/1999-4923/12/2/93intranasalnanoparticlebrainspinal cordtargetingrabies virus glycoprotein |
| spellingShingle | Eugene P. Chung Jennifer D. Cotter Alesia V. Prakapenka Rebecca L. Cook Danielle M. DiPerna Rachael W. Sirianni Targeting Small Molecule Delivery to the Brain and Spinal Cord via Intranasal Administration of Rabies Virus Glycoprotein (RVG29)-Modified PLGA Nanoparticles Pharmaceutics intranasal nanoparticle brain spinal cord targeting rabies virus glycoprotein |
| title | Targeting Small Molecule Delivery to the Brain and Spinal Cord via Intranasal Administration of Rabies Virus Glycoprotein (RVG29)-Modified PLGA Nanoparticles |
| title_full | Targeting Small Molecule Delivery to the Brain and Spinal Cord via Intranasal Administration of Rabies Virus Glycoprotein (RVG29)-Modified PLGA Nanoparticles |
| title_fullStr | Targeting Small Molecule Delivery to the Brain and Spinal Cord via Intranasal Administration of Rabies Virus Glycoprotein (RVG29)-Modified PLGA Nanoparticles |
| title_full_unstemmed | Targeting Small Molecule Delivery to the Brain and Spinal Cord via Intranasal Administration of Rabies Virus Glycoprotein (RVG29)-Modified PLGA Nanoparticles |
| title_short | Targeting Small Molecule Delivery to the Brain and Spinal Cord via Intranasal Administration of Rabies Virus Glycoprotein (RVG29)-Modified PLGA Nanoparticles |
| title_sort | targeting small molecule delivery to the brain and spinal cord via intranasal administration of rabies virus glycoprotein rvg29 modified plga nanoparticles |
| topic | intranasal nanoparticle brain spinal cord targeting rabies virus glycoprotein |
| url | https://www.mdpi.com/1999-4923/12/2/93 |
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