Kirtane, A. R. | Search bioRxiv

bioRxiv2025

Identification and Validation of Small Molecules with Mucin-Selective Regiospecific Binding in the Gastrointestinal Tract

Oral drug delivery is a widely used method of drug administration; however, achieving localized drug release at specific regions of the gastrointestinal (GI) tract is generally accomplished by using broad environmental differences. The GI tract is a complex system with regional differences in composition, such as selective expression of mucin glycoproteins in different organs. Here, we identify small molecule ligands that can selectively bind to the different mucins to localize drug delivery to the small intestine and stomach. We demonstrate up to a 10-fold increase in particle binding to these organs and up to a 4-fold increase in selectivity compared to chitosan. Additionally, we observe up to a 9-fold increase in budesonide concentration in the small intestine and a 25-fold increase in tetracycline concentration in the stomach. These results show that we have developed a versatile platform capable of sequestering a variety of drugs in certain GI tract organs.

bioengineering↗

bioRxiv2019

Computationally guided high-throughput design of self-assembling drug nanoparticles

Nanoformulations are transforming our capacity to effectively deliver and treat a myriad of conditions. However, many nanoformulation approaches still suffer from high production complexity and low drug loading. One potential solution relies on harnessing co-assembly of drugs and small molecular excipients to facilitate nanoparticle formation through solvent exchange without the need for chemical synthesis, generating nanoparticles with up to 95% drug loading. However, there is currently no understanding which of the millions of possible combinations of small molecules can result in the formation of these nanoparticles. Here we report the development of a high-throughput screening platform coupled to machine learning to enable the rapid evaluation of such nanoformulations. Our platform identified 101 novel self-assembling drug nanoparticles from 2.1 million pairings derived from 788 candidate drugs with one of 2686 excipients, spanning treatments for multiple diseases and often harnessing well-known food additives, vitamins, or approved drugs as carrier materials - with potential for accelerated approval and translation. Given their long-term stability and potential for clinical impact, we further characterize novel sorafenib-glycyrrhizin and terbinafine-taurocholic acid nanoparticles ex vivo and in vivo. We anticipate that this platform could accelerate the development of safer and more efficacious nanoformulations with high drug loadings for a wide range of therapeutics.

bioengineering↗