Planar Bioadhesive Microdevices: A New Technology for Oral Drug Delivery

Abstract

The oral route is the most convenient and least expensive route of drug administration. Yet, it is accompanied by many physiological barriers to drug uptake including low stomach pH, intestinal enzymes and transporters, mucosal barriers, and high intestinal fluid shear. While many drug delivery systems have been developed for oral drug administration, the physiological components of the gastro intestinal tract remain formidable barriers to drug uptake. Recently, microfabrication techniques have been applied to create micron-scale devices for oral drug delivery with a high degree of control over microdevice size, shape, chemical composition, drug release profile, and targeting ability. With precise control over device properties, microdevices can be fabricated with characteristics that provide increased adhesion for prolonged drug exposure, unidirectional release which serves to avoid luminal drug loss and enhance drug permeation, and protection of a drug payload from the harsh environment of the intestinal tract. Here we review the recent developments in microdevice technology and discuss the potential of these devices to overcome unsolved challenges in oral drug delivery.

Micro/nanofabricated platforms for oral drug delivery

“…Biochemical adhesion utilizing high-affinity interactions between a targeting ligand and specific moieties can provide highly specific binding to the small intestine or diseased tissue. However, one drawback to the use of biomolecules and other surface modifications to promote adhesion is degradation as a result of the low pH of the stomach and proteolytic and metabolic enzymes throughout the GI tract [63]. Therefore, molecular stability must be considered for surface modification of oral drug delivery platforms.…”

Current Trends in MEMS Drug Delivery Techniques

“…Microsystems for oral drug delivery are designed in such a manner so as to maximise their residence time in the gastrointestinal track and provide unidirectional release of drugs towards the intestinal epithelium and also regulate the release of drugs in a sustained manner. These properties make such devices important for not only improving the drug permeation but also improving its solubility and causing the degradation of drugs in such a way which makes them highly effective [23], [24]. Hence, the use of microdevices for oral drug delivery improves this mechanism by leaps and bounds and abolishes most of the barriers associated with oral drug delivery.…”

“…In this way, the movement of drugs is properly regulated into the blood stream, thus, preventing any harsh effects of the drugs on the patient and hence such systems lead to the improvement in the patient compliance. Physiological barriers to oral drug delivery (Adapted from [23]). …”

Physical Delivery of Macromolecules using High-Aspect Ratio Nanostructured Materials

“…However, these tissues have numerous chemical and physical defensive barriers, such as degradative enzymes, harsh pH conditions, tight junctions, and a mucus layer to prevent the entry of unwanted substances. 14,44,50,51 The mucus layer has a quick turnover time of 50–170 min to clear substances that do not directly interact with the cells. 51,52 Because of the viscous and motile nature of the mucus, therapeutic macromolecules take a longer time to diffuse into cells, increasing their susceptibility to degradation and removal.…”

“…51,52 Because of the viscous and motile nature of the mucus, therapeutic macromolecules take a longer time to diffuse into cells, increasing their susceptibility to degradation and removal. 50 The Desai group developed nanowire-coated systems to overcome the challenge of mucus layer protection. 14,15,45 NEMPs increase retention time up to 10-fold more than that of unmodified particles and improve device adhesion in vivo, as shown in Figure 7.…”