Enhancing specific drug delivery to increase efficacy and reduce toxicity
Successful disease management through treatment with a therapeutic is dependent on several factors:
- Half-life of the therapeutic in circulation: Once administered, a therapeutic is subject to a number of different mechanisms through which the body attempts to eliminate it. The more susceptible to these mechanisms, the shorter the time the therapeutic can survive in circulation, which reduces its impact in treating the disease. This can be managed by increasing either the dose used per treatment, and/or increasing the number of administrations per day (e.g. therapeutics that need to be taken twice or three times a day) in order to maintain an appropriate concentration in the blood to be effective against the disease. Alternatively, a therapeutic can be modified or packaged to protect it from rapid elimination, thus extending its half-life in circulation.
- Access of the therapeutic to the site of the disease: In the last decade, a new class of therapeutics has been developed based on the use of short oligonucleotides (RNA, or DNA). However, translating the promise from laboratory studies to human treatment successfully has been extremely challenging due to the inability to deliver this class of therapeutics to disease tissue. Preliminary success has been achieved by packaging the therapeutics in nanoparticles, but to date, this success has been limited to delivery to the eye compartment and the liver. Devising a nanoparticle technology that can expand the delivery of oligonucleotide therapeutics to a broad range of tissues will be a major advance for this therapeutic modality.
- Therapeutic Index: The viability of a therapeutic product and its utility in the market is impacted by the differential between its therapeutic efficacy (benefit) and toxicity, referred to as the therapeutic index. The target for a “good” therapeutic is to have a low effective concentration and a high toxic concentration which translates to a wide therapeutic index. Improving a therapeutic index can be accomplished by directing most of the therapeutic to the disease site and reducing the exposure of non-disease tissue. This specific targeting can be accomplished by packaging the therapeutic in delivery vehicles (e.g. nanoparticles) that are engineered to home-in preferentially on the disease tissue.