Proposed Implementation

Defining the End User

Our targeted end users are people currently undergoing chemotherapy and radiotherapy for treatment of cancer. In particular, patients in the early stages of cancer therapy, who have either no or mild oral mucositis would be ideal; thus, the patch would help prevent the initiation of oral mucositis and/or its development. Users with a more severe case of OM could also benefit from the product, though with an emphasis on its use as a barrier from irritants and its potential to prevent further spread to neighboring healthy cells.

Reviewing Existing Treatments

There are a few treatments on the market that are similar to GSHield in that they seek to cover the affected area with a patch. One notable example is Gelclair. Gelclair is a concentrated oral gel that contains the barrier-forming ingredients polyvinylpyrrolidone and sodium hyaluronate. When rinsed in the mouth, it forms an adherent barrier over the oral mucosa, shielding the mucosa from overstimulation. It does not have an alcohol or anesthetic base and so does not sting on application. We found that this mechanism appears to offer good pain relief in palliative care patients with oral lesions. Studies are currently investigating whether this barrier may improve the clinical signs by protecting the mucosa from injury, insult, or trauma. Another similar technology is Mugard, which is intended to be used prior to receiving chemotherapy.

Learn more about Gelclair and Mugard here:

However, our take on a patch aims to improve upon the concept. GSHield will be functionalized with glutathione to PREVENT formation of ulcers rather than simply forming a barrier and providing pain relief. While current technologies focus on treating the side effects, we hope to prevent the initiation of oral mucositis and prevent development into severe stages. It would also be a “smart” patch, responsive to oxidative stress conditions.

Proposed Mode of Use

The GSHield patch would be recommended by the patient’s oncologist and provided at the same place that they receive their therapy for convenience. The number of patches given at a single time would depend on the mode of therapy, dosage, and type of cancer.

OM is more common among those who receive radiotherapy than chemotherapy, and for radiotherapy, doses are received daily, 5 times a week for several weeks (NHS 2022). So, on the Friday of their cycle week, they would receive 5-15 patches to be used overnight. Patches may be applied to the mouth prior to any signs of symptoms. Alternatively, they may be applied at the onset symptoms but before severe pain (ex. the patient feels a rough patch forming in their mouth). Additionally, they may use patches as barriers against irritants while eating, as needed. The patches can be applied by the individual at home throughout the duration of the treatment period, and their allotment would be restocked on a weekly basis. A similar approach can be used for patients undergoing chemotherapy and combined therapy, with adjustments to the frequency and size of allotments.

Safety Measures

The main safety concern is preventing an accumulation of glutathione and/or preventing it from entering the tumor and decreasing the efficacy of therapy. While the spread of the glutathione will likely be relatively localized, as a precaution, there would be a limit placed on the number of applications of the patch per day; such a limit would be better defined after data is collected from in-vivo animal trials.

In early June, we had a meeting with Tzu-Chieh (Zijay) Tang, PhD, a research fellow at the Wyss Institute who developed Syn-SCOBY, a bacteria-yeast co-culture material, which is the technology we wanted to base our patch on. One concern that we discussed was the potential for colonization and infection by Saccharomyces cerevisae in the patch, which could disrupt the oral microbiome. However, S. cerevisiae is a food-grade yeast and thus, should be relatively safe. Additionally, the choice to structure the therapeutic as a patch rather than a topical helped to alleviate some of these concerns; a solid patch allows for most-to-all of the yeast to be removed in one motion, reducing the possibility of microbiome disruption. In the future, however, we may consider using a more commensal yeast or bacteria (ex. S. boulardii) for the glutathione production and potentially transfer the existing system from S. cerevisiae to the new organism.

Production Considerations

We also discussed several factors regarding the production of the patch with Tang, including the following:

  • Patch Size: The final size of the bacterial cellulose pellicle is constrained by the surface area that we allot it for growth. He suggested the use of a 96-well plate for the production of many pellicles. However, the size also constrains the amount of glutathione that can be produced, which is an important consideration that can be iterated upon in the future.
  • Porosity of BC: We want to ensure that the patch has a suitable level of porosity so that glutathione can exit the patch and make contact with layers of the oral epithelium. The tight network nanofibrils in bacterial cellulose can be a hindrance to the passage of larger compounds. However, with a pore size of 4 nm to 1000 µm under static conditions (Gao 2011), small molecules like glutathione should be able to pass through with ease.
  • Yeast-to-Bacteria Ratio: We want to ensure a favorable ratio between the yeast and the bacterial cellulose-producing E. coli, such that the final surface area of BC aligns with the amount of yeast present, keeping in mind that while some cells will be trapped in surface, 80-90% of present yeast cells will wash off. In the end, the yeast should be loosely affixed to the surface of the BC pellicle.
  • Product Storage: Tang suggested drying the pellicle to improve storage efficiency. Freeze drying and air drying were both suitable options. During this stage, the yeast should be able to express sugar (trehalose) to help resist desiccation. When ready for use, the pellicle would be rehydrated to revive the yeast before being applied to the patient.
  • Adhesion: Since this product is being applied to the inner mouth, Tang emphasized that the adhesive needed to be strong enough to hold while still being relatively easy to remove.

Other Challenges

One potential challenge to consider is medical adherence, especially when considering the product as a preventative measure. If the patient ceases to use the product, whether as a result of discomfort or apathy, it will ultimately impact the overall effectiveness of it to prevent severe stages of OM.

Additionally, we would want to consider the costs of production for this patch and work to optimize the process as much as possible. OM can be a cause of increased economic burden for cancer patients, and our patch would hopefully relieve some of that burden. At the same time, we want to ensure that the upfront cost of using multiple one-time-use patches does not further exacerbate existing economic barriers for lower income and working class patients.



Citations

  1. Ashrafi, Z., Lucia, L., & Krause, W. (2019). Bioengineering tunable porosity in bacterial nanocellulose matrices. Soft Matter, 15(45), 9359–9367. https://doi.org/10.1039/c9sm01895f
  2. Gao, C., Wan, Y., Yang, C. et al. Preparation and characterization of bacterial cellulose sponge with hierarchical pore structure as tissue engineering scaffold. J Porous Mater 18, 139–145 (2011). https://doi.org/10.1007/s10934-010-9364-6
  3. NHS. (2022, February 25). What happens: Radiotherapy. NHS choices. Retrieved October 11, 2022, from https://www.nhs.uk/conditions/radiotherapy/what-happens/