Authors: Takashi Nakano, Shakila B. Rizwan, David M. A. Myint, Jason Gray, Sean M. Mackay, Paul Harris, Christopher G. Perk, Brian I. Hyland, Ruth Empson, Eng Wui Tan, Keshav M. Dani, John NJ Reynolds, and Jeffery R. Wickens
Published online February 21, 2022
“Previous work measuring release in brain slices from previously injected animals has shown that liposomes retain their ability to repeatedly release drug after one week in vivo [28]. Further work is needed to determine the time course over which liposomal nanostructures remain intact and responsive to ultrasound stimulation after injection in vivo. Another challenge is to minimize leakage from liposomes, while preserving the ability to trigger release. In the current work, we show that the HGN-liposomes successfully encapsulated KA and could be injected into the brain and remain there for one week, without causing damage to surrounding tissue. Leakage can be minimized by increasing the stability of the liposome formulation. However, there is a trade-off between the stability of liposomes and sensitivity to stimulation, which requires systematic study to arrive at optimal formulations.
Ideally, treatment for epilepsy should prevent seizures before they occur. However, in one third of patients existing treatments are not effective in preventing seizures, and treatment-resistant epilepsy is associated with significant morbidity and mortality [48,49]. Existing technology is not yet capable of predicting seizures with clinically useful reliability. However, the technology for seizure detection already exists. For example, Kim et al. [50] concluded from a review of the literature that ‘… the state-of-the-art seizure detection system performance is sufficient to build a robust and reliable wearable device that could be used for daily seizure monitoring and classification.’ What is needed, therefore, is a means to deliver the drug immediately on the first sign of a seizure. Here we aimed to demonstrate proof of principle that seizures can be arrested almost instantaneously provided HGN-liposomes are preloaded in the brain. However, the practical use of this approach will require the future development of tools for applying US or laser stimulation in an ambulatory patient setting, as well as new technology for infiltrating the HGN-liposomes into the brain. Extensive studies of pharmacokinetics, pharmacodynamics, and toxicity will also be needed to determine the utility and safety of the technology in humans.”
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“The present study focused on epileptic seizures in particular, because of the challenges of long-term treatment with systemic antiepileptic drugs, and the large number of patients with drug-resistant epilepsy. The ability to deliver high concentrations of drug to target areas on demand, while keeping drug concentrations low at other sites and times may enable the use of drugs that are effective when applied locally, but unsuitable for systemic use, because of their effects on other systems. Muscimol is one example of such a drug, which has been found unsuitable for systemic application, but potentially effective when applied locally. For such applications, the development of technology to move HGN-liposomes across the BBB and anchor them with the brain parenchyma would be necessary. Further work is needed to determine the utility and safety of the technology in humans, particularly concerning the pharmacokinetics, pharmacodynamics, and toxicity of HGN-liposomes and their constituents. Technology for detection of seizures and application of US stimulation in ambulatory patients will also be needed. If these problems can be solved, HGN-liposomes have the potential to be developed into a new treatment for responsive forms of epilepsy” (Nakano et al., 2022).
Through this study, the world of epilepsy can expand a little bigger. Introducing a new drug delivery system with HGN-liposomes that can promote seizure control quickly. This study was tested on animals and it showed positive signs of reduction in seizure activity in the brain. The drug used, muscimol, allows doctors to make precise releases of the dosage. These advancements allow for the relief of seizure anxiety among the epileptic community. Finding procedures that can go in between the routine medication route and surgery route provides exciting pathways. We can open our eye sights to more avenues of exploration. What if these new drugs with the help of a device could have the ability to detect the start of a seizure and track the pattern that the seizure makes in the brain. It records that pattern and is proactive on administering a new drug dosage the next time it detects the same pattern. the patient wouldn’t even know they were going to have a seizure if the device would alert them it detected one.
References
Nakano, T., Rizwan, S. B., Myint, D. M., Gray, J., Mackay, S. M., Harris, P., Perk, C. G., Hyland, B. I., Empson, R., Tan, E. W., Dani, K. M., Reynolds, J. N., & Wickens, J. R. (2022b). An on-demand drug delivery system for control of epileptiform seizures. Pharmaceutics, 14(2), 468. https://doi.org/10.3390/pharmaceutics14020468
