Crystal Sanchez
Research Mentor(s): Omolola Adefeso
Research Mentor School/College/Department: Department of Chemical Engineering
Presentation Date: 08/03/2022
Presentation Type: Poster
Poster Number: 10
Session: Session II: 1:30 – 2:20pm
Room: League Ballroom
Authors: Crystal Sanchez, Michael LaRue Felder, PhD Candidate, Omolola Eniola-Adefeso, PhD
Abstract
Osteoarthritis (OA) is the most common form of arthritis, affecting about 32.5 million adults in the United States alone. It occurs when protective cartilage within a joint wears down over time, typically caused by injury or overuse. OA patients are often prescribed medication to alleviate symptoms such as pain and reduced joint mobility. As such, it is important to understand the pharmacokinetics of drugs that are administered intra-articularly, or directly into the joint. Therapeutics that are used to treat OA symptoms are ever-evolving, from small molecule drugs like corticosteroids to large immunosuppressive protein therapies. Thus, there is a need for a model that can mimic the clearance properties of arthritic joints for the purpose of evaluating the effectiveness of new treatments.
A model was created using an agarose hydrogel acting as the barrier separating the intra-articular space from the bloodstream, whereby drug clearance is assumed to be mediated by diffusion from the joint. An array of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and corticosteroids were injected into hydrogels to study their release from the model intra-articular space. The hydrogel was inserted into a container of excess phosphate-buffered saline (PBS) that the drug diffused into, and samples were removed from this outer volume at 30-minute increments for 5 hours. This experiment was done using hydrogels of varying agarose concentrations to determine the impact of hydrogel concentration on drug release rates. Samples were analyzed with Ultraviolet-Visible Spectroscopy. UV-Vis is a technique that measures the amount of UV or visible light that is absorbed by a sample in comparison to a reference or blank sample. A plain PBS sample served as the blank sample. Calibration samples with known amounts of drug were made and absorbance values corresponding to each concentration were used to form a linear equation relating the absorbance to the concentration. This equation was used to determine the concentration of the drug in each time sample.
To ultimately validate the model, a literature search was conducted to find studies where NSAIDs were injected directly into the synovium of human OA patients, and synovial fluid samples were taken to determine the drug clearance rate. We hypothesize that we will be able to find an agarose gel concentration that significantly mimics the drug clearance patterns shown in human clinical studies. Once a particular model shows statistically significant similarities to these studies, it can be implemented for OA treatment testing applications.
