A review published in the journal, Open epilepsy, explored nanomedical drug candidates based on polymeric and lipid nanosupports for the management of epilepsy.
To study: Biodegradable nanoparticles for the treatment of epilepsy: from current advances to future challenges. Image Credit: SewCream / Shutterstock.com
Because epilepsy is a common neurological disorder, it is important to understand its pathophysiology and to undertake research that can help design an effective treatment. The introduction of nanotechnology has advanced medicine in various fields, and therefore its incorporation into the treatment of epilepsy would be ideally suited.
Why new treatments for epilepsy are needed
Epilepsy is a neurological disorder affecting the central nervous system through abnormal electrical activity in areas of the brain such as the hippocampus and cortex. Subsequently, this results in symptoms such as frequent seizures, consisting of surges of electrical activity in the brain that temporarily affect its normal functioning.
Common ligands for the surface functionalization of polymeric nanoparticles. Â© Bonilla, L. et al (2021)
Neurodegeneration, which is of concern for this disease, can be described biochemically as having a large amount of calcium ions entering neurons – the main neurotoxic process that results in cell death and eventual degeneration of neurons.
The World Health Organization (WHO) has estimated that epilepsy affects more than 50 million people worldwide, with 5 million new diagnoses occurring each year.
Currently, although there are treatments that can help manage the disorder, there is no known cure, and anti-epileptic drugs are not always effective.
This makes this area of ââmedicine essential for researchers to develop innovative therapies. With the emergence of nanomedicine, the capacity for advanced therapy may be a promising development.
Limitations of current antiepileptic treatments
Antiepileptic drugs (ASMs) are one approach to manage symptoms of a seizure, with the first ASM being used at the start of the 20e century and second generation ASM drugs used as adjuvants in the 1990s. However, although there was an improvement in effects, adverse effects were also observed.
Other limitations included a narrow therapeutic window and multiple interactions. This led to the development of third generation ASM, which allowed better control of neuronal excitability to prevent seizure.
These drugs work to decrease or modulate the excitability of neurons, which stops the expansion of electrical discharges in the brain. With various types of ASMs available, the mechanism of action differs, such as some ASMs targeting the excitatory synapse and working on blocking the activity of inotropic glutamate receptors, including AMPA or NMDA receptors.
Other types of ASM available can target extrasynaptic membrane ion channels that are voltage dependent, including Ca2+, N / A+, or K+ canals. This is important because these channels have an important function that can control the progression of epileptic symptoms, including restoring the neuronal membrane to its optimal state.
In addition, antiepileptic drugs can also target inhibitory synapses and reduce neuron excitability through their mechanism of action on the GABAergic system.
Main advantages and disadvantages of polymer and lipid nanoparticles. Â© Bonilla, L. et al (2021)
However, as mentioned earlier, a number of these antiepileptic drugs cause a lack of response in patients and therefore improvement with nanomedical incorporation could be a potential method to increase the effectiveness of epilepsy treatments.
Biodegradable nanoparticles for epilepsy treatments
The introduction of nanotechnology and nanoparticles to advance medicine has had significant benefits for patient care, with research being deepened in many different areas.
One of these benefits of using nanotechnology is that nanoparticles, including polymeric nanoparticles (PNPs) are used to cross the blood-brain barrier due to their nanometric size. This barrier which is generally beneficial for the exchange of nutrients and the prevention of any damage to the brain microenvironment can be a challenge for conventional drugs which find it difficult to cross due to their oversized size.
Nanomedicine has enabled the advancement of antiepileptic drugs in order to cross the barrier and increase the concentration of these drugs in the central nervous system. The use of polymer nanoparticles can also allow selectivity which can help target specific receptors through the functionalization of the polymer matrix surface which can guide the particles to their therapeutic target.
The polymer matrix material allows the particles to be specialized in order to have specific properties for their desired function and this can be formed by various polymers or a combination of different polymers. The polymers most commonly used for this purpose include polylactide (PLA), poly (lactide-co-glycolide) (PLGA), chitosan, and polyethyleneimine (PEI).
Researchers developing PNPs that encapsulate epilepsy drugs made from PLGA nanoparticles have shown results such as reduced doses with a single dose every 24 hours still having a positive effect on seizure control. In addition, an accumulation of these particles may even have had a neuroprotective effect on the brain.
Other studies included results of antiepileptic drugs encapsulated in PNPs that were 30 times more effective than when used freely without nanosupport, with PNPs having the additional effect of overcoming P-glycoprotein-mediated drug resistance.
With the narrow therapeutic margin of antiepileptic drugs for epilepsy as well as drug resistance over time, this area of ââmedicine requires further development. The use of polymer nanoparticles to encapsulate these drugs resulted in higher efficacy, with sustained seizures.
The use of these biodegradable particles ensures the absence of toxicity for the patients due to their breakdown into non-toxic bioproducts at the target site, which also allows for prolonged administration of the drug. This safer and more effective alternative to delivering epileptic drugs to patients reduces side effects and the need for multiple administrations.
The search for future therapies may target strategies to overcome permeability limitations within the blood brain barrier as well as efficient drug delivery in the CNS, for which polymer nanoparticles may be a promising tool. In addition, the use of nanoparticles for transdermal drug delivery would also be an interesting research point to provide long term treatment.
However, translating nanotransporters for clinical use is a difficult challenge that may require government regulatory policies to resolve. This pharmaceutical and medical process is quite complex and expensive, preventing the advancement of critical patient care. With the use of responsible government policies, the development of treatments using nanotransporters for the treatment of epilepsy can really be advanced.
Continue reading: Progression of pulmonary drug delivery with nanoparticles.
Bonilla, L., Esteruelas, G., Ettcheto, M., Espina, M., GarcÃa, M., Camins, A., Souto, E., Cano, A. and SÃ¡nchez â LÃ³pez, E., (2021) Biodegradable nanoparticles for the treatment of epilepsy: from current advances to future challenges. Open epilepsy, Available at: https://onlinelibrary.wiley.com/doi/full/10.1002/epi4.12567
Devinsky, O., Vezzani, A., O’Brien, T., Jette, N., Scheffer, I., de Curtis, M. and Perucca, P., (2018) Epilepsy. Nature examines the beginnings of diseases, 4 (1). Available at: https://doi.org/10.1038/nrdp.2018.24