Breakthrough in Oral Delivery of IV Medications

An exciting breakthrough in drug delivery systems has been uncovered, showing promise for allowing intravenous (IV) medications to be taken orally. This discovery, led by a team of researchers from the University of Texas Health Science Center at San Antonio (UT Health San Antonio), Duke University, and the University of Arkansas for Medical Sciences (UAMS), has the potential to revolutionize drug delivery methods, particularly for large and polar drugs that have traditionally been challenging to administer.

Overview of the Discovery

Published in Cell, the study introduces a novel approach termed chemical endocytic medicinal chemistry. This innovative strategy focuses on enhancing the cellular uptake mechanisms of large and polar drugs by optimizing their interactions with a specific protein receptor known as CD36, which is prevalent on the surfaces of many cells.

“Chemical endocytic medicinal chemistry has the potential to impact every aspect of endocytic drugs from drug discovery and development to clinical practice.” – Dr. Hong-yu Li, Lead Researcher

Understanding Drug Delivery Mechanisms

Researchers have long recognized the difficulties associated with administering larger drug molecules, especially those exceeding 500 Daltons (Da), due to limitations in passive diffusion. The introduction of induced proximity in recent years has paved the way for novel drug discovery methods. This process involves using smaller molecules to induce interactions between proteins, allowing for more effective drug actions.

CD36 and Endocytic Uptake

The study demonstrates that CD36 can mediate the endocytosis of compounds ranging from 543 to 2,145 Da, which is significant due to the size constraints that traditional methods impose on drug development. This is critical in expanding the catalog of potential drug candidates that can be formulated as induced proximity drugs.

Initial Findings and Experimental Results

A series of experiments conducted showcased the efficacy of this chemical endocytic medicinal chemistry approach. Notably, the research team verified the capability of optimized CD36 interaction to facilitate the uptake of proteolysis targeting chimeras (PROTACs)—large molecular compounds that possess distinct biological functionalities.

This unexpected result shifts paradigms within the pharmaceutical industry, as historically, scientists believed that larger molecules could not effectively traverse cellular membranes due to limited understanding of their endocytic uptake routes.

Implications for Drug Development

Dr. Li emphasizes that this transformative approach could necessitate a complete reevaluation of how effectiveness, pharmacokinetics, and toxicity are assessed by regulatory bodies such as the Food and Drug Administration (FDA).

Patient Stratification

Moreover, CD36 expression levels vary significantly in patients, particularly in cases of prostate cancer, indicating that this discovery could lead to personalized treatment options that exploit these differences.

Future Perspectives

Looking beyond CD36, researchers anticipate that other membrane receptors could similarly be targeted to enhance drug efficacy and bioavailability. Over the next few decades, the implications of this discovery may catalyze significant advancements in medicinal chemistry and therapeutic applications across various medical domains, including life-threatening diseases and chronic conditions.

As the field evolves, the incorporation of this strategy is expected to improve opportunities for effective drug delivery and minimize barriers traditionally faced in drug development.

Further Reading and Resources

For those interested in the detailed research findings, see the study by Zhengyu Wang et al., titled CD36-mediated endocytosis of proteolysis-targeting chimeras, published in Cell in 2025.

Additional background on endocytic mediators is available through various medicinal chemistry publications and databases.

This document has been reviewed for accuracy and reliability by Science X.