Abstract
Apomorphine (APO), a potent treatment for Parkinson's disease, is only administered parenterally either as intermittent injections or as an infusion. This is due to extensive hepatic “first pass” metabolism. Prolonged delivery through buccal mucosa may be potential substitute for parenteral infusions. To investigate this concept of buccal mucosal delivery, permeability ex vivo studies were performed through excised porcine buccal mucosa by utilizing Ussing diffusion chamber. Permeability rates were assessed for APO from simulated saliva medium at pH 7.4 as well as with utilization of different permeability modifying methods. Lowering the pH to 5.9 decreased permeability rate six-fold, while addition of ethanol: propylene glycol solution elevated it four-fold. Addition of nano-scale lipospheres to the donor compartment delayed the accumulation of APO at the receiver side, prolongating the lag-time from one to approx. three hours. These findings were strengthened by results obtained with co-administration of permeability markers (standards) atenolol and metoprolol. Simulation of the obtained permeability rates to in vivo setup in human showed therapeutically relevant plasma levels when using the outcomes of the current study. These findings verify the novel concept of APO prolonged release buccal administration as a noninvasive substitute for parenteral infusions in treating Parkinson's disease.
| Original language | English |
|---|---|
| Pages (from-to) | 2729-2734 |
| Number of pages | 6 |
| Journal | Journal of Pharmaceutical Sciences |
| Volume | 109 |
| Issue number | 9 |
| DOIs | |
| State | Published - Sep 2020 |
| Externally published | Yes |
Bibliographical note
Publisher Copyright:© 2020
Funding
We wish to highly acknowledge the willingness and hospitality of Dr. Joseph A Nicolazzo from the Monash University, Melbourne, Australia to host Constantin Itin in his laboratory for an internship period, and his and Dr. Liang Jin's skillful guidance and training in isolation of buccal mucosa and conduction of ex vivo experiments in Ussing diffusion chambers. The traveling expenses of this internship were financially supported by a grant from “The Batsheva de Rothschild Fund for The Advancement of Science in Israel” for which it is gratefully acknowledged. We wish to highly acknowledge the willingness and hospitality of Dr. Joseph A Nicolazzo from the Monash University, Melbourne, Australia to host Constantin Itin in his laboratory for an internship period, and his and Dr. Liang Jin's skillful guidance and training in isolation of buccal mucosa and conduction of ex vivo experiments in Ussing diffusion chambers. The traveling expenses of this internship were financially supported by a grant from “The Batsheva de Rothschild Fund for The Advancement of Science in Israel” for which it is gratefully acknowledged. A. Hoffman and A. Domb are affiliated with the David R. Bloom Center for Pharmacy at The Hebrew University and with the Multidisciplinary Center on Cannabinoid Research. Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
| Funders | Funder number |
|---|---|
| Batsheva de Rothschild Fund | |
| Monash University | |
| Hebrew University of Jerusalem |
Keywords
- Apomorphine
- Buccal
- Buccal delivery
- Controlled delivery
- Lipid nanoparticles
- Paracellular transport
- Permeation enhancer
- Transcellular transport
- Ussing diffusion chamber
- pH
