Breakthrough in Drug Delivery: Oral Administration of IV Medications

A team of researchers has made a significant discovery that could transform the way intravenous medications are administered, allowing them to be taken orally. This innovative approach, led by scientists from the University of Texas Health Science Center at San Antonio, in collaboration with Duke University and the University of Arkansas for Medical Sciences, focuses on enhancing the cellular uptake of large and polar drugs.

The study, recently published in the journal Cell, introduces a novel strategy known as chemical endocytic medicinal chemistry. This strategy aims to optimize the delivery of endocytic drugs, potentially revolutionizing drug design and development. The research team, under the guidance of a medicinal chemistry expert, discovered that drug molecules can be engineered to interact more effectively with CD36, a protein receptor present on many cell surfaces. By improving these chemical interactions, the researchers enhanced the natural function of CD36, thereby increasing the uptake of larger and more polar drug compounds into cells.

According to the lead researcher, this method could make it feasible for any drug currently administered via intravenous routes to be taken orally. Furthermore, it may facilitate the ability of drugs to penetrate the blood-brain barrier, which is crucial for treating conditions such as brain cancer and dementia.

Traditionally, the development of small-molecule drugs has been constrained by the 'Rule of 5,' which posits that molecules exceeding 500 Daltons in size are typically ineffective due to challenges related to cellular access and bioavailability. However, this recent discovery challenges that notion by chemically enhancing CD36-mediated uptake, thus amplifying the efficiency with which larger and polar molecules can enter target cells.

The research team validated their findings by demonstrating that large and polar chemical compounds, with sizes ranging from 543 to 2,145 Daltons, could be effectively internalized using this new strategy. The results were corroborated through independent experiments conducted by each collaborating institution.

This breakthrough prompts a reevaluation of traditional drug development processes, which have historically focused on optimizing chemical compounds for passive diffusion into cells. The new chemical endocytic approach could lead to a paradigm shift, addressing challenges related to permeability, solubility, and stability.

Moreover, the discovery has important implications for patient treatment. Analysis of prostate cancer tissues revealed varying levels of CD36 expression among patients, suggesting that some may respond differently to certain cancer therapies. The research team believes that by optimizing CD36 engagement, they could tailor treatments more precisely based on individual differences in CD36 expression.

Looking ahead, the researchers are investigating additional cell receptors that may be targeted for similar enhancement of drug uptake. With high levels of CD36 present in the intestine, brain, and skin, this approach holds promise for improving the delivery and effectiveness of medications, ultimately increasing oral bioavailability and facilitating delivery across the blood-brain barrier or through the skin.

As this field of research continues to evolve, the potential for transforming drug discovery and development over the coming decades appears substantial, paving the way for novel therapies for previously challenging diseases.