Imagine a world where medications can be administered with unparalleled precision and efficiency. Thanks to Cholestosome, this vision is becoming a reality. This groundbreaking research, conducted by a team of brilliant minds right on the Niagara University campus, created, designed, and developed a cutting-edge drug delivery system known as the Cholestosome. This technology boasts not only unexpected but also incredibly powerful properties for drug delivery.

There are multiple areas of research where Cholestosome technology is of great value. The Cholestosome drug delivery technology is being used to develop a general anti-viral therapeutic. The technology is being used to target triple negative breast cancer as well as several other disease needs. One exciting component of our research focuses on addressing the critical issue of lead poisoning, which is recognized as a significant global health threat, especially for children. Currently, there is no effective treatment for lead poisoning. In our laboratory, we are developing a groundbreaking therapeutic using Cholestosome technology. This innovative approach enables the delivery of an agent that can remove lead from neural cells. The Cholestosome delivers an agent to the neural cells that is released and then binds to the lead inside the cells. Our therapeutic reduces the lead levels, offering a potential solution to this widespread problem. This pioneering treatment could even be administered orally, making it a truly groundbreaking advancement.

The concept of Cholestosomes as potential vesicles originated from a computer model of esters packed in layers, which exhibited vesicle-like surfaces. We then recognized the Cholestosome’s role as a protective cocoon for its contents. As we further developed the technology, we discovered that we could encapsulate various substances within the Cholestosome. Microscopy studies confirmed the vesicle structure, which could be adjusted in size based on experimental parameters. These robust vesicles demonstrated resilience against extreme pH levels and bile salt degradation, while successfully delivering payloads into cells. This breakthrough opened up possibilities for both oral and intracellular delivery methods. 

Cholestosomes were tested to see if they could deliver a fluorescent molecule (fluorescein isothiocyanate, FITC) into various cell types. 

Cholestosomes have demonstrated the ability to load into various cell types, as shown in a study on immune cell loading. White blood cells (WBCs) readily internalize Cholestosome-encapsulated FITC, indicating their potential for active immunotherapy. Loading dendritic cells with Cholestosomes offers a promising approach for personalized immunotherapies, as they can carry active antigens and adjuvants. This activation of immune cells against tumors can transform “cold” tumors into “hot” ones.

In terms of intracellular targeting, a study focused on the entry of vancomycin into MCF-7 cells. The fluorescence images revealed that FITC-vancomycin-Cholestosomes at a concentration 100 times lower than FITC-vancomycin alone resulted in significantly greater cellular uptake. Even at higher concentrations, FITC-vancomycin alone did not achieve the same level of loading as FITC-vancomycin-Cholestosomes. Importantly, the presence of high amounts of FITC-vancomycin-Cholestosomes did not have any adverse effects on the MCF-7 cells. These findings highlight the remarkable efficiency of Cholestosomes in enhancing cellular uptake, potentially offering new possibilities for targeted drug delivery. 

To explore brain loading and genetic delivery, we investigated the potential of Cholestosomes to deliver plasmids which were functionalized without the need for transfection. Additionally, we explored the encapsulation of insulin as a test molecule, taking advantage of the stability of Cholestosomes in low pH and resistance to bile salt degradation. This suggested the possibility of oral delivery via the chylomicron pathway, which was confirmed in vitro using Caco-2 intestinal epithelial cells.

In the Caco-2 assay, we observed the passage of Cholestosome-encapsulated FITC-labeled insulin through to the basolateral side, forming large complexes after induction of chylomicron production by the cells. This led to a proof-of-principle test of oral insulin delivery, demonstrating that Cholestosomes could deliver the payload into the bloodstream and tissues throughout the body. Considering the ability to target various neural cell types, this opened up the potential for Cholestosome-encapsulated insulin as a treatment for Alzheimer’s disease.

Collaborating with Dandona et al., we found that Cholestosome-delivered insulin affected both inflammatory and Alzheimer’s markers in neural cell lines. Furthermore, recent studies on a cell model of COVID-19 showed a 60% reduction in infectivity using Cholestosomes. These versatile vesicles can deliver zinc ions to inhibit viral replication and transport antibodies inside cells to prevent the release of infection. This breakthrough offers a powerful tool in combating future pandemics, and ongoing research focuses on intracellular delivery of Cholestosome-encapsulated therapeutics against various viral infections. 

If you’re interested in learning more about how you can take part in this groundbreaking research, contact us today.