ArticleProceedings of the National Academy of Sciences of the United States of America2022
A deep eutectic-based, self-emulsifying subcutaneous depot system for apomorphine therapy in Parkinson's disease.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 29 citations in OpenAlex.
- Advancements in Therapeutic Deep Eutectic Solvents as Multifunctional Transdermal Delivery Systems.Pharmaceutics · 2026Review
- Capric Acid-Based Therapeutic Deep Eutectic Systems: A Focused Review Within the Framework of Deep Eutectic Solvents.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Review
- Ionic liquids and their potential use in development and improvement of drug delivery systems: evidence of their tendency to promote drug accumulation in the brain.Pharmaceutical development and technology · 2024Review
- Therapeutic drug monitoring in Parkinson's disease.Journal of neural transmission (Vienna, Austria : 1996) · 2024Review
- HSPiP, Computational, and Thermodynamic Model-Based Optimized Solvents for Subcutaneous Delivery of Tolterodine Tartrate and GastroPlus‑Based In Vivo Prediction in Humans: Part II.AAPS PharmSciTech · 2024Article
- Synthetic aporphine alkaloids are potential therapeutics for Leigh syndrome.Scientific reports · 2024Article
- Pharmaceutical applications of therapeutic deep eutectic systems (THEDES) in maximising drug delivery.Heliyon · 2024Review
- HSPiP, Computational, and Thermodynamic Model-Based Optimized Solvents for Subcutaneous Delivery of Tolterodine Tartrate and GastroPlus-Based In Vivo Prediction in Humans: Part I.AAPS PharmSciTech · 2024Article
- Fabrication and Characterization of Dissolving Microneedles for Transdermal Drug Delivery of Apomorphine Hydrochloride in Parkinson's Disease.Pharmaceutical research · 2024Article
- Potentials of ionic liquids to overcome physical and biological barriers.Advanced drug delivery reviews · 2024Review
- Deep Eutectic Solvents for Subcutaneous Delivery of Protein Therapeutics.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- An overview of biomedical applications of choline geranate (CAGE): a major breakthrough in drug delivery.RSC advances · 2022Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Apomorphine, a dopamine agonist, is a highly effective therapeutic to prevent intermittent off episodes in advanced Parkinson's disease. However, its short systemic half-life necessitates three injections per day. Such a frequent dosing regimen imposes a significant compliance challenge, especially given the nature of the disease. Here, we report a deep eutectic-based formulation that slows the release of apomorphine after subcutaneous injection and extends its pharmacokinetics to convert the current three-injections-a-day therapy into an every-other-day therapy. The formulation comprises a homogeneous mixture of a deep eutectic solvent choline-geranate, a cosolvent n-methyl-pyrrolidone, a stabilizer polyethylene glycol, and water, which spontaneously emulsifies into a microemulsion upon injection in the subcutaneous space, thereby entrapping apomorphine and significantly slowing its release. Ex vivo studies with gels and rat skin demonstrate this self-emulsification process as the mechanism of action for sustained release. In vivo pharmacokinetics studies in rats and pigs further confirmed the extended release and improvement over the clinical comparator Apokyn. In vivo pharmacokinetics, supported by a pharmacokinetic simulation, demonstrate that the deep eutectic formulation reported here allows the maintenance of the therapeutic drug concentration in plasma in humans with a dosing regimen of approximately three injections per week compared to the current clinical practice of three injections per day.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.