Implantable Nanofluidics to Tackle Obesity
A nanofluidic implantable system achieves sustained and constant low-dose delivery of a therapeutic for the treatment of obesity
Obesity and type-2 diabetes are global epidemics in which prevalence has been increasing steadily worldwide. Although lifestyle modifications such as eating healthy and staying active can help individuals lose weight and increase their sensitivity to insulin, the initial inertia to burn excess fat is often very difficult to overcome. Individuals likely would benefit from a safe therapeutic approach that can help to change their activity levels and increase energy. This study describes the development of an innovative delivery system referred to as nanochannel membrane device (NMD) for the sustained and constant low-dose delivery of the therapeutic GC-1 (sobetirome), a thyroid-hormone mimetic molecule, for intraabdominal weight loss. The reported nanofluidic system is minimally invasive compared with current surgical approaches and devices used to treat obesity, which can have serious complications and undesirable adverse effects. The approach is demonstrated as a four-month pilot study in a spontaneously obese non-human primate.
The authors use physical confinement to allow for sustained and constant release of GC-1, similar to the natural thyroid hormone with a lack of associated detrimental effects. Constant release of this thyroid receptor beta selective agonist is achieved as it travels from a drug reservoir through nanochannels (250 nanometers) and is continuously released in the body in small amounts over the desired time range. Fabricating the device in this way provides three major advantages: first, the ability to induce weight loss and normalize glucose and insulin levels; second, the capacity to continuously deliver over an extended period of time; and third, sustained-release without moving components or actuation.
The results presented in a diseased non-human primate model are greatly relevant for clinical translation. The drug itself was already initiated in Phase I clinical trials for a different indication (hyperlipidemia). The approach has potential for a massive positive impact on patients providing a safe and effective therapeutic strategy that avoids issues of compliance. The device would help patients achieve improvements as measured by traditional medical metrics while also allowing patients to benefit from minimal daily life disruptions conventionally associated with current multi-drug modalities and drug delivery systems.
By: Mauro Ferrari, Biomedical Microdevices