Executive Summary : | Degradable drug delivery systems are crucial for clinical applications, as they allow for temporally controlled release of therapeutics. The exact amount of therapeutic released in a given timeframe is essential for determining the administration dose, increasing efficacy, reducing toxicity, and reducing costs. In vitro studies are commonly used to determine release kinetics, but measuring in vivo release kinetics has been challenging due to diffusion barriers, sink conditions, and inflammatory reactions. Traditional methods like serial euthanasia or plasma sampling have limitations, including the inability to measure release kinetics in the same animal, ethical considerations, and lack of accuracy in determining the exact amount of therapeutic released at the site of administration. In vivo fluorescence- or magnetic resonance-based imaging has also limitations, such as lack of in vivo penetration depth or difficulty conjugating probes to the therapeutic molecule. This study proposes using a photoacoustic imaging technique to quantify in vivo release from a degradable polymeric system and estimate the effective diffusion coefficient in tissues. By applying mathematical models to the data, the values of these parameters will be estimated for the same model-therapeutic in both conditions. Comparing the differences in in vitro and in vivo diffusion coefficients across different model-therapeutics and model-drug delivery systems will help arrive at an effective diffusion coefficient at specific tissue sites. This study aims to determine tissue-specific effective diffusion coefficients that can be used to develop safer and more efficacious drug delivery systems for clinical use. |