A deep eutectic-based, self-emulsifying subcutaneous depot system for apomorphine therapy in Parkinson’s disease

Jayoung Kim, Yongsheng Gao, Zongmin Zhao, Danika Rodrigues, Eden E.L. Tanner, Kelly Ibsen, Pradip K. Sasmal, Rajasekhar Jaladi, Shanavas Alikunju, Samir Mitragotri

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


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.

Original languageEnglish
Article numbere2110450119
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number9
StatePublished - 1 Mar 2022


  • Apomorphine
  • Deep eutectic
  • Depot
  • Ionic liquid
  • Parkinson’s


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