Planar Bioadhesive Microdevices for Enhanced Oral Drug Delivery

Oral delivery is a preferred route of administration as it is less invasive, provides patient compliance, and less costly. However, the harsh physiological conditions of the gastrointestinal tract, along with an array of intestinal enzymes and high shear fluid flow reduce the therapeutic efficacy of oral drugs. Although several delivery paradigms including microparticles have been developed, their non-uniform size distributions and symmetrical radial-directional drug release limit oral bioavailability. To overcome these issues, we demonstrate the use of microfabricated thin, planar, asymmetric, poly(methyl methacrylate); PMMA biocompatible microdevices to facilitate the delivery of oral drugs across the intestinal epithelium. Multiple reservoirs were introduced into the PMMA microdevices for an independent and controlled release of differentially tagged model drugs (BSA) across an in vitro caco-2 monolayer. Intestinal epithelia-specific targeting protein, tomato lectin was also conjugated to the microdevice surface to provide enhanced bioadhesion. An in vivo mouse model was used to study the bioadhesion, retention, and delivery of a poorly absorbable and poorly soluble model drug Acyclovir across the intestine. The use of unidirectional, flat microdevices, with multiple drug loading capacity can prove to be a simple yet powerful method to greatly enhance the therapeutic efficacy of oral drugs.