A luminal unfolding microneedle injector for oral delivery of macromolecules.

Abstract

Insulin and other injectable biologic drugs have transformed the treatment of patients suffering from diabetes^1,2, yet patients and healthcare providers often prefer to use and prescribe less effective orally dosed medications^3-5. Compared with subcutaneously administered drugs, oral formulations create less patient discomfort⁴, show greater chemical stability at high temperatures⁶, and do not 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, 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 luminal unfolding microneedle injector provided a faster pharmacokinetic uptake profile and a systemic uptake >10% of that of a subcutaneous injection over a 4-h 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.