Non-invasive, continuous oral delivery of solid levodopa-carbidopa for management of Parkinson’s disease
Abstract When short plasma half-life drugs act only briefly, they require frequent or continuous administration. We report the engineering of a non-invasive oral drug delivery system for long-term, continuous administration of these drugs. Their non-invasive, long-term, continuous administration at...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-11-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-024-78145-4 |
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| author | William L. Murch John Spiridigliozzi Adam Heller Ephraim Heller |
| author_facet | William L. Murch John Spiridigliozzi Adam Heller Ephraim Heller |
| author_sort | William L. Murch |
| collection | DOAJ |
| description | Abstract When short plasma half-life drugs act only briefly, they require frequent or continuous administration. We report the engineering of a non-invasive oral drug delivery system for long-term, continuous administration of these drugs. Their non-invasive, long-term, continuous administration at daily doses exceeding 100 mg has, for many years, been considered an insurmountable challenge. We show that over 1200 mg/day of 4:1 levodopa-carbidopa (LD-CD) can be non-invasively and continuously extruded when formulated as a semisolid paste, loaded with 63%w/w of the solid drugs. The drug delivery system comprises a reusable orthodontic retainer with a co-molded pocket into which the patient inserts after each meal a new 1 mL propellant-driven, prefilled, disposable, drug delivery extruder. The paste is delivered to the lingual side of the teeth where it is mixed with saliva and swallowed. As reported elsewhere, a 15-day, 16 patient open label clinical trial of the drug delivery system continuously extruding LD-CD paste significantly reduces the variability of the plasma LD concentration and alleviates symptoms of advanced Parkinson’s disease (PD) as compared to LD-CD tablets. |
| format | Article |
| id | doaj-art-27bf1ac536ef48e4a5f03d76f1e47a00 |
| institution | OA Journals |
| issn | 2045-2322 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-27bf1ac536ef48e4a5f03d76f1e47a002025-08-20T02:13:55ZengNature PortfolioScientific Reports2045-23222024-11-011411910.1038/s41598-024-78145-4Non-invasive, continuous oral delivery of solid levodopa-carbidopa for management of Parkinson’s diseaseWilliam L. Murch0John Spiridigliozzi1Adam Heller2Ephraim Heller3synAgile CorporationsynAgile CorporationsynAgile CorporationsynAgile CorporationAbstract When short plasma half-life drugs act only briefly, they require frequent or continuous administration. We report the engineering of a non-invasive oral drug delivery system for long-term, continuous administration of these drugs. Their non-invasive, long-term, continuous administration at daily doses exceeding 100 mg has, for many years, been considered an insurmountable challenge. We show that over 1200 mg/day of 4:1 levodopa-carbidopa (LD-CD) can be non-invasively and continuously extruded when formulated as a semisolid paste, loaded with 63%w/w of the solid drugs. The drug delivery system comprises a reusable orthodontic retainer with a co-molded pocket into which the patient inserts after each meal a new 1 mL propellant-driven, prefilled, disposable, drug delivery extruder. The paste is delivered to the lingual side of the teeth where it is mixed with saliva and swallowed. As reported elsewhere, a 15-day, 16 patient open label clinical trial of the drug delivery system continuously extruding LD-CD paste significantly reduces the variability of the plasma LD concentration and alleviates symptoms of advanced Parkinson’s disease (PD) as compared to LD-CD tablets.https://doi.org/10.1038/s41598-024-78145-4 |
| spellingShingle | William L. Murch John Spiridigliozzi Adam Heller Ephraim Heller Non-invasive, continuous oral delivery of solid levodopa-carbidopa for management of Parkinson’s disease Scientific Reports |
| title | Non-invasive, continuous oral delivery of solid levodopa-carbidopa for management of Parkinson’s disease |
| title_full | Non-invasive, continuous oral delivery of solid levodopa-carbidopa for management of Parkinson’s disease |
| title_fullStr | Non-invasive, continuous oral delivery of solid levodopa-carbidopa for management of Parkinson’s disease |
| title_full_unstemmed | Non-invasive, continuous oral delivery of solid levodopa-carbidopa for management of Parkinson’s disease |
| title_short | Non-invasive, continuous oral delivery of solid levodopa-carbidopa for management of Parkinson’s disease |
| title_sort | non invasive continuous oral delivery of solid levodopa carbidopa for management of parkinson s disease |
| url | https://doi.org/10.1038/s41598-024-78145-4 |
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