A Luminal Unfolding Microneedle Injector for Oral Delivery of Macromolecules

Abstract

Insulin and other injectable biologic drugs transformed the treatment of patients suffering from diabetes1,2, yet patients and healthcare providers often prefer to use and prescribe less effective orally dosed medications3–5. Compared to subcutaneously administered drugs, oral formulations create less patient discomfort4, demonstrate greater chemical stability at high temperatures6, and don’t generate biohazardous needle waste7. An oral dosage form for biologic medications is ideal; however, macromolecule drugs are not readily absorbed into the bloodstream through the gastrointestinal tract8. We developed an ingestible capsule, termed the Luminal Unfolding Microneedle Injector (LUMI), which allows for the oral delivery of biologic drugs by rapidly propelling dissolvable drug-loaded microneedles into intestinal tissue using a set of unfolding arms. During ex vivo human and in vivo swine studies the device consistently delivered the microneedles to the tissue without causing complete thickness perforations. Using insulin as a model drug we showed that, when actuated, the LUMI provided a faster pharmacokinetic uptake profile and a systemic uptake greater than 10% compared to a subcutaneous injection over a 4 hour sampling period. With the ability to load a multitude of microneedle formulations, the device can serve as a platform to orally deliver therapeutic doses of macromolecule drugs.