Is Poor Bioavailability Holding Back Modern Medicine?

23 Dec 2021

  Scientist inspecting contents of test tube in the light

When a person is battling a life-changing diagnosis, the last thing they need is for their treatment regimen to become an additional burden, or even worse, to be told that no disease-modifying treatment option is available. For all of the advances we have seen in modern medicine, too many medicines are still unavailable via oral administration, where superior patient compliance, fewer sterility constraints, and a range of dose flexibility benefits both patients and their health care providersi. While at the same time, too many promising medicinal compounds are abandoned in early development because of structural limitations. In many instances, these shortcomings are the result of the same cause, poor bioavailability.

Bioavailability is the portion of a medicine that enters circulation when introduced in the body, allowing that medicine to have an active effect for the patient. While several factors impact the ultimate bioavailability of a compound, one of the most frequent causes of low bioavailability is poor solubility or the compound’s ability to dissolve in a pure solvent.

As a result, solubility is a critical factor in determining what concentration of a medicine is needed to generate patient benefit. The more insoluble a compound, the higher dose required to reach therapeutic plasma concentrations necessary to achieve a result, but higher doses bring a host of additional challenges including potential toxicity issues that may force patients to abandon treatment. And this problem isn’t limited to oral medications, more than 40% of new molecular entities (NME) developed in the health care industry are practically insolubleii. Preventing many of the most promising therapies from ever delivering their full potential for patients.

But what if there was a way to alter these compounds through precision bioengineering to dramatically improve their bioavailability? At Double Rainbow, we are leveraging our breakthrough PRISMTM enzyme modification platform to radically alter the solubility, and ultimately the bioavailability, of new and existing medicines.

To date, we have consistently shown that our modified compounds are capable of delivering dramatic fold changes in solubility compared to parent compounds, while promising data from an in vivo model has shown certain glycosylation motifs confer surprising impact on bioavailability. These results continue to validate our belief that our proprietary precision glycosylation can successfully leverage the natural sugar receptors within the body to maximize a medicine’s bioavailability at lower doses, even through oral administration.

Tests are ongoing as we continue to push the limits of our technology, but our team remains focused on our goal of delivering safer, more effective medicines to the patients we serve.


iYellela SRK. Pharmaceutical technologies for enhancing oral bioavailability of poorly soluble drugs. Journal of Bioequivalence & Bioavailability. 2010;2(2):28 – 36

iiSharma D, Soni M, Kumar S, Gupta GD. Solubility enhancement — eminent role in poorly soluble drugs. Research Journal of Pharmacy and Technology. 2009;2(2):220 – 224.

A portrait of   Jing Ke Weng

Written By Jing-Ke Weng, PhD

Jing-Ke Weng is Co-Founder of Double Rainbow. Currently, he is a member of the Whitehead Institute for Biomedical Research, and an Associate Professor of Biology at Massachusetts Institute of Technology.

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