ICF: The development of a chemotherapeutic containing mucoadhesive patch for the treatment of oral epithelial dysplasia
Lead Research Organisation:
University of Sheffield
Department Name: Clinical Dentistry
Abstract
What is the context of the research?
This research is aimed at developing a new and much more effective treatment for a disease called oral epithelial dysplasia (OED). OED affects 2 in every 100 people, and occurs in the tissue that lines the mouth where it presents as white or red regions that cannot be wiped away. Over time, these affected areas have the potential to turn into mouth cancer. OED is diagnosed by taking a tissue sample (biopsy) of the affected area and examining it under a microscope. Currently there is no consensus about how to manage or treat OED. Surgical removal remains the most common form of treatment for severely affected tissue. However, to date, no treatment has proven effective at stopping OED from progressing to mouth cancer. Recent experimental studies have reported that some existing or new chemotherapeutic drugs have the potential to interfere with the way OED progresses to cancer and so might be used as new treatments for people with OED, if they can be applied to the affected mouth tissue. Unfortunately, applying drugs to the lining of the mouth with any medication remains challenging because of its wet surface. Retention of gels, mouthwashes, creams and ointments is poor due to the actions of saliva, swallowing, and tongue and jaw movements. However, recent advances in materials made using a technique called electrospinning offers the potential to develop a patch that can adhere tightly to the lining of the mouth and release drugs directly to the area to which it is applied.
What will this research achieve?
The aim of this research is to develop an adhesive patch that can stick to the lining of the mouth and release drugs that can treat OED. We will optimise and rigorously test the effectiveness and safety of the system in the laboratory. We will also study how these drugs affect OED cells within tissues and how this facilitates treatment. These data will provide extremely useful information to take this type of treatment forward to clinical trials.
Why is the development of new treatments important?
The rate at which OED turns into oral cancer is 20%. Approximately 12,500 cases of head and neck cancer are diagnosed each year in the UK, survival rates remain poor at 59% 5 years after diagnosis, causing 4,000 deaths a year. Worldwide, deaths are more prevalent with mouth cancer placed as the 6th most common cancer. Mouth cancer is a largely preventable disease with early detection and management of OED critical to avoiding cancer progression. Current management and treatment options are inadequate and fail to address how the disease develops. Developing a more effective treatment for OED has the potential to prevent progression to mouth cancer, ultimately saving lives.
How will the research be conducted?
Electrospinning is a technique whereby chemicals called polymers are turned from a liquid into a fine fibre mesh that looks similar to candyfloss, using a high electrical voltage. Drugs can be mixed into the polymer solution so that they are incorporated into the polymer fibres when electrospun. These fibres can then be made into patches, similar to a small plaster. We have developed a special blend of polymers that adhere tightly to the lining of the mouth and deliver drugs when applied. Here, we will develop and optimise the production of new patches to contain a number of drugs that will specifically target OED cells. We will measure how quickly and how much of the drugs are released from patches over time. Once the drugs are released from the patches, we will assess their effectiveness at either killing or altering OED cells, firstly using experiments on cells and tissues cultured in the laboratory. Finally, we will take the most promising drug-containing patches and use these to treat rats that have developed experimental OED in order to determine if these treatments work on living tissue before moving towards clinical trial experiments.
This research is aimed at developing a new and much more effective treatment for a disease called oral epithelial dysplasia (OED). OED affects 2 in every 100 people, and occurs in the tissue that lines the mouth where it presents as white or red regions that cannot be wiped away. Over time, these affected areas have the potential to turn into mouth cancer. OED is diagnosed by taking a tissue sample (biopsy) of the affected area and examining it under a microscope. Currently there is no consensus about how to manage or treat OED. Surgical removal remains the most common form of treatment for severely affected tissue. However, to date, no treatment has proven effective at stopping OED from progressing to mouth cancer. Recent experimental studies have reported that some existing or new chemotherapeutic drugs have the potential to interfere with the way OED progresses to cancer and so might be used as new treatments for people with OED, if they can be applied to the affected mouth tissue. Unfortunately, applying drugs to the lining of the mouth with any medication remains challenging because of its wet surface. Retention of gels, mouthwashes, creams and ointments is poor due to the actions of saliva, swallowing, and tongue and jaw movements. However, recent advances in materials made using a technique called electrospinning offers the potential to develop a patch that can adhere tightly to the lining of the mouth and release drugs directly to the area to which it is applied.
What will this research achieve?
The aim of this research is to develop an adhesive patch that can stick to the lining of the mouth and release drugs that can treat OED. We will optimise and rigorously test the effectiveness and safety of the system in the laboratory. We will also study how these drugs affect OED cells within tissues and how this facilitates treatment. These data will provide extremely useful information to take this type of treatment forward to clinical trials.
Why is the development of new treatments important?
The rate at which OED turns into oral cancer is 20%. Approximately 12,500 cases of head and neck cancer are diagnosed each year in the UK, survival rates remain poor at 59% 5 years after diagnosis, causing 4,000 deaths a year. Worldwide, deaths are more prevalent with mouth cancer placed as the 6th most common cancer. Mouth cancer is a largely preventable disease with early detection and management of OED critical to avoiding cancer progression. Current management and treatment options are inadequate and fail to address how the disease develops. Developing a more effective treatment for OED has the potential to prevent progression to mouth cancer, ultimately saving lives.
How will the research be conducted?
Electrospinning is a technique whereby chemicals called polymers are turned from a liquid into a fine fibre mesh that looks similar to candyfloss, using a high electrical voltage. Drugs can be mixed into the polymer solution so that they are incorporated into the polymer fibres when electrospun. These fibres can then be made into patches, similar to a small plaster. We have developed a special blend of polymers that adhere tightly to the lining of the mouth and deliver drugs when applied. Here, we will develop and optimise the production of new patches to contain a number of drugs that will specifically target OED cells. We will measure how quickly and how much of the drugs are released from patches over time. Once the drugs are released from the patches, we will assess their effectiveness at either killing or altering OED cells, firstly using experiments on cells and tissues cultured in the laboratory. Finally, we will take the most promising drug-containing patches and use these to treat rats that have developed experimental OED in order to determine if these treatments work on living tissue before moving towards clinical trial experiments.
Technical Summary
Oral epithelial dysplasia (OED) is a potentially malignant disorder that affects the oral mucosa. Approximately 20% of OED lesions undergo malignant transformation to oral cancer. Currently, there is no standard treatment and the moist environment of the mouth and saliva flow makes targeted drug delivery difficult, making OED one of the most challenging oral diseases to manage and treat. The objective of this study is to tackle this current state by developing a drug-containing mucoadhesive patch that can adhere tightly and deliver chemotherapeutics directly to OED lesions when applied topically, preventing their progression to cancer. Using polymer and electrospinning technology, drugs already identified as potential chemotherapeutics for OED will be loaded into microfiber mucoadhesive patches, and their physiochemical and adhesive properties along with drug release profiles characterised using a multitude of quantitative analytical techniques. Drug activity upon release from the patches will be initially examined using a tissue engineered 3D in vitro cell-based system that accurately mimics human OED lesions. Drug-loaded patches that show the greatest efficacy following histological and key OED marker analysis in the in vitro system will be taken forward for further preclinical testing in a chemically-induced (4-nitroquinoline-1-oxide) in vivo rat animal model of OED. Results arising from this study would open up the possibility of progression to clinical trials and exploitation of intellectual property with current and other industrial collaborators or funders. If successful, such a chemotherapeutic-loaded patch would have the potential to directly advance alternative treatment options for a disease that currently has limited and ineffective therapies. In the long-term, mucoadhesive patches would radically transform current treatment regimes, substantially improving patient survival rates.
