A groundbreaking discovery by researchers at UT Health San Antonio has the potential to transform how certain medications are administered, particularly for diseases like brain cancer and Alzheimer’s. The team, led by Dr. Hong-yu Li, developed a novel approach called chemical endocytic medicinal chemistry that could enable intravenous drugs to be taken orally. This innovation not only broadens the scope of treatments but also enhances drug delivery across barriers such as the blood-brain barrier, opening new avenues for personalized medicine.
In recent years, scientists have faced significant challenges in developing oral formulations for complex, large-molecule drugs due to their inability to passively diffuse into cells. However, this new strategy leverages the body's natural protein receptors, specifically CD36, to facilitate cellular uptake of these compounds. By optimizing interactions with CD36, the researchers demonstrated that even molecules exceeding 500 Daltons can efficiently enter target cells, overturning long-held beliefs about drug absorption mechanisms.
The study began with an investigation into the role of CD36 in lipid transport and metabolism, revealing its unexpected potential to enhance the cellular intake of large, polar chemical drugs. Through meticulous experimentation, the team validated the efficacy of this approach using proteolysis-targeting chimeras (PROTACs), a class of large molecular compounds. Their findings showed rapid and effective uptake, challenging previous assumptions about molecular size limitations in drug delivery.
Beyond enabling oral administration, this discovery could significantly impact drug development processes. Traditionally, designing drugs involved balancing permeability, solubility, and stability for passive diffusion. The new paradigm shifts focus toward receptor-mediated cellular entry, potentially altering how regulatory agencies evaluate drug efficacy, pharmacokinetics, and toxicity. Moreover, variations in CD36 expression among individuals may explain differing responses to certain cancer treatments, paving the way for precision therapies tailored to individual biology.
Looking ahead, Dr. Li envisions expanding research to explore other cell receptors capable of facilitating chemical endocytosis. With high levels of CD36 receptors present in intestinal, brain, and skin cells, this strategy holds promise for improving drug bioavailability via oral ingestion, crossing the blood-brain barrier, or transdermal application. Such advancements could redefine drug discovery over the next two decades, establishing a new frontier in medicinal chemistry and offering hope for previously untreatable conditions.
This transformative work underscores San Antonio's growing reputation as a hub for biomedical innovation. As UT Health San Antonio continues to lead pioneering research through collaborations with institutions like Duke University and the University of Arkansas for Medical Sciences, the future of medicine inches closer to realizing the full potential of personalized and precise treatments.