The objective of this Phase I study is to develop an intra-oral, adhesive film which can cover and protect various mouth sores and deliver low doses of pain relieving lidocaine and anti-inflammatory doxycycline to the sore site. In particular, we will focus on developing the adhesive film for treating canker sores, which is a ubiquitous problem affecting many people across the world. In this project, we introduce two innovative aspects in developing intra-oral films. First, a strongly adherent intra-oral polymer which will keep the film attached to the canker site with an inert backing polymer to keep the film from adhering to other intra-oral surfaces. The backing surface will protect the canker site from saliva and irritation from other sources. Second, the intra-oral film has the ability to deliver two-drug combination from this film in a controlled fashion to reduce pain and suffering. The objective of this project will be achieved through the following two specific aims. The first specific aim is to develop a new film formulation consisting of a highly adherent layer for securing the film inside the oral cavity. A series of films will be developed and will be evaluated for their buccal adhesiveness. The most promising films proceed to the drug loading test. The film will be comprised of polyethylenimine-catechol, a polymer inspired by the proteins used by mussels and barnacles to adhere strongly to surfaces, with a drug eluting layer and a backing layer. These layers will be designed from materials which are non-toxic and dissolvable in water. These films will be designed to be flexible and elastic so as to not be damaged by processes such as talking or eating. The adhesive layer is such that the film will not be removed from the sore surface unless carefully pulled away by fingers. Our preliminary study showed that the films could stay in place until being peeled away by fingers. The second specific aim is to load drugs into the film formulation so that they can be released in a controlled manner. Lidocaine will be loaded in the films and the elution kinetics will be determined in. In addition to lidocaine an anti-inflammatory, low dose doxycycline, will also be released to relieve the redness and swelling associated with canker sores. The drugs will be loaded by co-dissolving the drug in with the polymer. This duration of release will be adjusted by changing the drug loading and the polymer concentration so that the release can last for at least several hours. The unique approach in our application is to utilize polyethylenimine-catechol as the adhesive layer that is known to provide excellent adhesion under wet conditions. At the end of this project, Akina will develop a new intra-oral, drug eluting, adhesive film that can reduce pain and suffering associated with canker sores. Phase II of this project will focus on animal studies showing the efficacy of the intra-oral film to move into the human clinical applications.
Public Health Relevance: The objective of this Phase I study is to develop an intra-oral, adhesive film which can cover and protect various mouth sores and deliver low doses of pain relieving lidocaine and anti-inflammatory doxycycline to the sore site. These films will overcome problems associated with current technology which generally delivers medication in a non-localized manner or for a short period of time. This technology will provide relief for a ubiquitous and generally untreated problem.
Thesaurus Terms: 1,2-Benzenediol;1,2-Dihydroxybenzene;2-(Diethylamino)-N-(2,6-Dimethylphenyl)Acetamide;2-2etn-2mephacn;2-Diethylamino-2',6'-Acetoxylidide;2-Naphthacenecarboxamide, 4-(Dimethylamino)-1,4,4a,5,5a,6,11,12a-Octahydro-3,5,10,12,12a-Pentahydroxy-6-Methyl-1,11-Dioxo-, (4s-(4alpha,4aalpha,5alpha,5aalpha,6alpha,12aalpha))-;2-Hydroxyphenol;Adhesions;Adhesiveness;Adhesives;Affect;Animals;Anti-Inflammatories;Anti-Inflammatory Agents;Anti-Inflammatory;Antiinflammatories;Antiinflammatory Agents;Aphthae;Aphthous Stomatitis;Aphthous Ulcer;Back;Barnacles;Buccal Cavity;Buccal Cavity Head And Neck;Canker Sore;Catechols;Cavitas Oris;Chemicals;Diffusion;Dorsum;Dose;Doxycycline;Drug Combinations;Drug Formulations;Drugs;Eating;Film;Fingers;Food Intake;Formulation;Healed;Hour;Human;Hydrogen Oxide;Juice;Kinetics;Loinc Axis 2 Property;Lidocaine;Lignocaine;Man (Taxonomy);Mechanics;Medication;Membrane;Modern Man;Mouth;Mouth Sore;Mussels;Omega-Diethylamino-2,6-Dimethylacetanilide;Oral;Oral Cavity;Oranges;Pain;Pain Control;Pain Therapy;Pain Management;Painful;Permeability;Pharmaceutic Preparations;Pharmaceutical Preparations;Phase;Phase I Study;Polymers;Process;Property;Proteins;Pyrocatechols;Redness;Saliva;Secure;Series;Site;Source;Surface;Swelling;Technology;Testing;Thick;Thickness;Thoracica;Time;Vibramycin;Water;Alpha-6-Deoxyoxytetracycline;Clinical Applicability;Clinical Application;Controlled Release;Design;Designing;Drug/Agent;Flexibility;Flexible;Gene Product;Healing;Improved;Innovate;Innovation;Innovative;Irritation;Mechanical;Membrane Structure;Novel;O-Dihydroxybenzenes;Ortho-Dihydroxybenzenes;Phase 1 Study
