A Historical Review of Brain Drug Delivery
The history of brain drug delivery is reviewed beginning with the first demonstration, in 1914, that a drug for syphilis, salvarsan, did not enter the brain, due to the presence of a blood–brain barrier (BBB). Owing to restricted transport across the BBB, FDA-approved drugs for the CNS have been gen...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-06-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/6/1283 |
| _version_ | 1797483288721358848 |
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| author | William M. Pardridge |
| author_facet | William M. Pardridge |
| author_sort | William M. Pardridge |
| collection | DOAJ |
| description | The history of brain drug delivery is reviewed beginning with the first demonstration, in 1914, that a drug for syphilis, salvarsan, did not enter the brain, due to the presence of a blood–brain barrier (BBB). Owing to restricted transport across the BBB, FDA-approved drugs for the CNS have been generally limited to lipid-soluble small molecules. Drugs that do not cross the BBB can be re-engineered for transport on endogenous BBB carrier-mediated transport and receptor-mediated transport systems, which were identified during the 1970s–1980s. By the 1990s, a multitude of brain drug delivery technologies emerged, including trans-cranial delivery, CSF delivery, BBB disruption, lipid carriers, prodrugs, stem cells, exosomes, nanoparticles, gene therapy, and biologics. The advantages and limitations of each of these brain drug delivery technologies are critically reviewed. |
| first_indexed | 2024-03-09T22:44:52Z |
| format | Article |
| id | doaj.art-c6269489b0de40d684315bd8d3065bb8 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T22:44:52Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-c6269489b0de40d684315bd8d3065bb82023-11-23T18:31:13ZengMDPI AGPharmaceutics1999-49232022-06-01146128310.3390/pharmaceutics14061283A Historical Review of Brain Drug DeliveryWilliam M. Pardridge0Department of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USAThe history of brain drug delivery is reviewed beginning with the first demonstration, in 1914, that a drug for syphilis, salvarsan, did not enter the brain, due to the presence of a blood–brain barrier (BBB). Owing to restricted transport across the BBB, FDA-approved drugs for the CNS have been generally limited to lipid-soluble small molecules. Drugs that do not cross the BBB can be re-engineered for transport on endogenous BBB carrier-mediated transport and receptor-mediated transport systems, which were identified during the 1970s–1980s. By the 1990s, a multitude of brain drug delivery technologies emerged, including trans-cranial delivery, CSF delivery, BBB disruption, lipid carriers, prodrugs, stem cells, exosomes, nanoparticles, gene therapy, and biologics. The advantages and limitations of each of these brain drug delivery technologies are critically reviewed.https://www.mdpi.com/1999-4923/14/6/1283blood–brain barrierendotheliumreceptor-mediated transportcarrier-mediated transportgenetic engineeringIgG fusion proteins |
| spellingShingle | William M. Pardridge A Historical Review of Brain Drug Delivery Pharmaceutics blood–brain barrier endothelium receptor-mediated transport carrier-mediated transport genetic engineering IgG fusion proteins |
| title | A Historical Review of Brain Drug Delivery |
| title_full | A Historical Review of Brain Drug Delivery |
| title_fullStr | A Historical Review of Brain Drug Delivery |
| title_full_unstemmed | A Historical Review of Brain Drug Delivery |
| title_short | A Historical Review of Brain Drug Delivery |
| title_sort | historical review of brain drug delivery |
| topic | blood–brain barrier endothelium receptor-mediated transport carrier-mediated transport genetic engineering IgG fusion proteins |
| url | https://www.mdpi.com/1999-4923/14/6/1283 |
| work_keys_str_mv | AT williammpardridge ahistoricalreviewofbraindrugdelivery AT williammpardridge historicalreviewofbraindrugdelivery |