Bioengineering Approaches for Extracellular Vesicles as Advanced Drug Delivery Systems

The development of more effective drug delivery systems (DDSs) is crucial for advancing medical treatments. Traditional DDSs methods often struggle with issues such as poor solubility, limited tissue penetration, and nonspecific drug distribution. Recently, nano-based DDSs, particularly Lipid Nanoparticles (LNPs) and Extracellular Vesicles (EVs), have gained attention for their potential to enhance therapeutic outcomes. EVs, naturally occurring lipid bilayer particles involved in intercellular communication, are particularly promising in cancer therapy due to their ability to cross biological barriers like the blood-brain barrier and their innate targeting capabilities. Despite their promise, EV-based drug delivery faces several challenges, including scalability, enhanced drug loading efficiency, and improved storage methods. To address these issues, a multidisciplinary approach was employed, focusing on both biological and engineering aspects of DDSs. This included designing a microfluidic platform for the efficient production of drug-loaded Mesenchymal Stem Cell-derived EVs. The microfluidic approach not only improved efficiency but also preserved the functionality of both the drug and EVs, making it applicable to a wide range of therapeutic molecules. Additionally, milk whey was explored as a cost-effective, biocompatible source of EVs for drug delivery, offering high yields and supporting sustainability within a circular economy framework. The scalability and efficiency of producing drug-loaded milk-derived EVs using Tangential Flow Filtration demonstrated its potential for broader therapeutic applications. Another focus of the research involved the development of injectable EV-based hydrogels. By integrating the targeting properties of EVs with the versatility of hydrogels, these advancements created new opportunities for designing sophisticated delivery systems that could offer enhanced specificity and efficacy. Lastly, hybrid systems were developed, merging the targeting potential of EVs with the gene-carrying efficiency of LNPs. The successful development of these hybrids laid the foundation for innovative gene-delivery platforms that harness the strengths of both DDSs. In conclusion, this research introduced novel devices, materials and methods that addressed the current limitations in DDSs, providing new tools for targeted therapy and opening new possibilities for treating various diseases.