Sampriti Roy, University of Calcutta
When we see conventional drug administration, especially in cases of neurodegenerative diseases like Parkinson’s, the commonly prescribed drugs are those that require metabolism to be absorbed into the central nervous system. However, it has been found that the number of drugs reaching the brain after metabolism is very small. We must also keep in mind the factor of “up-regulation” of drugs, i.e. the fact that patients have to increase their drug doses as time passes by. The patients, to overcome metabolic problems, are left with no choice but to receive “rescue” pump-based direct delivery of drugs into the jejunum, as seen in the case of L-DOPA-carbidopa intestinal gel used to treat Parkinson’s disease. In such cases, if an active drug can be directly administered into the brain, the results could be highly transformative to the present treatment procedures as well as to the patients. Fortunately, a new drug has found a way to do just that.
According to a recent study by Julie Tzu-Wen Wang et al., a supramolecular gel can now ensure that drugs for neurodegenerative diseases can be administered through the nose- a pathway where rapid absorption into the bloodstream is seen through nasal epithelia. The scientists have designed a simple two-component supramolecular hydrogel using benzaldehyde and glutamine amide derivative having characteristics like a fitting rheological performance and the ability to undergo rapid self-healing that make it suitable for use in nasal drug delivery
The access that the nasal pathway provides the drug to the trigeminal and olfactory nerves strikes out the need to cross the blood-brain barrier and opens up the possibility of direct brain delivery. At a time when we are witnessing rising cases of neurodegenerative diseases like Alzheimer’s and Parkinson’s, the development in discussion holds considerable significance.
• What are supramolecular gels?
A Supramolecular gel can be defined as a soft material in which a “solid-like network”, that assembles itself from a low-molecular-weight gelator (LWMG), immobilizes a phase that is “liquid-like. (The gel may transform to solution-state if there is a disruption in the non-covalent forces in the architecture of the gel). They also possess soft rheological properties.
These gels have been attracting a lot of attention in recent times due to their high-end application in several areas. These include tissue engineering, environmental remediation (oil recovery, etc.), sensors, regenerative medicine, etc.
It must also be noted that in comparison to polymer gel systems previously studied, supramolecular gel systems are fully reversible materials that are easy to modify synthetically. They also maintain the ability to be formulated with several additives that might potentiate the delivery of the drug and its stability.
• Why they important in drug delivery?
Supramolecular gels can encapsulate APIs or active pharmaceutical ingredients within their structures and consequently, control their delivery in a variety of ways. The release of the APIs can be slow or rapid. This is why supramolecular gels based on LWMGs have a lot of potential in the field of drug delivery.
The goal kept in mind, in this case, was rapid drug release in the nasal cavity. The other way would be pretty undesirable as well as challenging since mucous is cleared out from the cavity at short intervals. So, with the average clearance half-life in the nasal cavity being about 15 minutes, rapid release of API is extremely important.
• What is an “ideal” supramolecular gel?
It was reasoned by the researchers that the ideal supramolecular gel would have the following characteristics:
i) It would need sheer thinning and capacity to recover so that it can be administered through the nose using a solution spray or injection. It would then form a thin gel film in situ, coating the nasal epithelia.
ii) The gel should be made with simple, low toxicity components and be easily degraded into “non-assembling units”. This would limit the chance that self-assembling structures form and accumulate in the nasal cavity when the patient is exposed long-term to the delivery vehicle.
iii) The gel should be compatible with drugs that are neurologically active and be capable of rapid release of the drug.
• The study and results obtained:
The model drug in the study was L-DOPA, a drug used to treat neurodegenerative diseases like Parkinson’s. Some of the interesting findings from the study are:
Upon injection through a syringe, it was observed that the gel initially exhibited shear-thinning behavior and acted as a solution, however, on standing after injection, a full sample-spanning gel would once again form. This type of “self-healing” capacity was said to be required of a gel for nasal delivery. This will allow the gel to be applied to the nasal cavity (for example via a nasal spray), and then reform a gel in situ to ensure effective contact with the nasal epithelium.
It has been reported that the gel can be loaded with the drug L-DOPA, without causing disturbance to the gel structure. The drug is largely mobile in the “liquid-like” phase of the gel and the mobile L-DOPA was observed to be released from the gel rapidly.
It was observed that when L-DOPA was injected intranasally as a solution, some of it went to the GI tract. However, when a gelator was used, the overall formulation was seen to be in the nasal cavity and this prevented drainage into the nasopharynx and GI tract.
When L-DOPA’s nasal administration was compared to intravenous administration, it was found that the nasal delivery gel achieved 2.1x more blood uptake and 4.1x more brain uptake 10 minutes after the administration.
Supramolecular gel-mediated intranasal drug delivery approach can thus be said to have the ability to achieve effective levels of drugs in the brain more rapidly than drug administration methods that require metabolism. Having shown promising results in experiments, this new finding is sure to be of great therapeutic value in the long run to treat debilitating and costly brain disorders like neurodegenerative diseases, brain malignancies, and psychiatric diseases.
Also read: Venomous humans: An intriguing concept
Source: Wang, J. T.-W., Rodrigo, A. C., Patterson, A. K., Hawkins, K., Aly, M. M. S., Sun, J., Al, K. T., Smith, D. K., Enhanced Delivery of Neuroactive Drugs via Nasal Delivery with a Self-Healing Supramolecular Gel. Adv. Sci. 2021, 2101058. https://doi.org/10.1002/advs.202101058
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