Researcher(s)
- Ryann Chatfield, Biomedical Engineering, University of Delaware
Faculty Mentor(s)
- Jason Gleghorn, Biomedical Engineering, University of Delaware
Abstract
One of the main challenges in treating metastatic cancer is targeting metastases, which often begin in the lymph nodes (LNs). Due to tightly regulated transport, many chemotherapeutics fail to penetrate the LN, leaving metastatic cells viable and allowing the disease to progress. In recent years, new delivery systems have been developed to improve drug transport into the LNs, including nanoparticles and local injectable technologies; however, these still have limitations, including rapid clearance, off-target accumulation, and incomplete dosing. Therefore, there is a need for a drug delivery vehicle that allows for targeted delivery to the LN that both enhances delivery efficiency and reduces off-target toxicities. Our lab has developed a microparticle (MP) system to deliver small-molecule chemotherapeutics to the LN using a Trojan horse strategy. In previous generations, we have demonstrated that the delivery vehicle can effectively target the LN; however, the drug encapsulation and release kinetics were suboptimal. Therefore, we aimed to design a microparticle core with a higher encapsulation efficiency and controllable loading and release to improve delivery efficiency. First, we validated methods for multi-phase droplet generation for tunable-sized MPs. Second, we demonstrated that alginate MPs exhibit effective encapsulation and release rates of small molecules, which vary as a function of alginate concentration. Finally, we confirmed that a small-molecule chemotherapeutic effectively neutralizes 4T1 cancer cells after loading and release, indicating that alginate is a suitable material for microparticle-based drug delivery vehicles. Altogether, these findings demonstrate that the microparticles serve as an effective and customizable drug delivery platform, enabling tunable encapsulation and sustained release profiles. By enhancing the controllability of our lymph node-targeted system, this approach offers greater treatment precision and improved biodistribution, building meaningfully upon our prior platform advancements.