Emerging microtechnologies for the development of oral drug delivery devices

Abstract

The development of oral drug delivery platforms for administering therapeutics in a safe and effective manner across the gastrointestinal epithelium is of much importance. A variety of delivery systems such as enterically coated tablets, capsules, particles, and liposomes have been developed to improve oral bioavailability of drugs. However, orally administered drugs suffer from poor localization and therapeutic efficacy due to various physiological conditions such as low pH, and high shear intestinal fluid flow. Novel platforms combining controlled release, improved adhesion, tissue penetration, and selective intestinal targeting may overcome these issues and potentially diminish the toxicity and high frequency of administration associated with conventional oral delivery. Microfabrication along with appropriate surface chemistry, provide a means to fabricate these platforms en masse with flexibility in tailoring the shape, size, reservoir volume, and surface characteristics of microdevices. Moreover, the same technology can be used to include integrated circuit technology and sensors for designing sophisticated autonomous drug delivery devices that promise to significantly improve point of care diagnostic and therapeutic medical applications. This review sheds light on some of the fabrication techniques and addresses a few of the microfabricated devices that can be effectively used for controlled oral drug delivery applications.

Figure 1

(a) Schematic structure of the intestinal epithelium through which the oral drug has to pass across to reach the blood plasma. (b) The model concentration versus time profiles for conventional and controlled release drug delivery devices. Also shown are the model profiles demonstrating multiple pulsatile releases for different drugs that can be achieved using novel microfabricated multireservoir drug delivery devices.

Figure 2

Schematic designs for opening and closing holes in a drug reservoir using the hydrogel based artificial muscle concept. (a) Plunger configuration, (b) Tube configuration, and (c) Sphincter configuration [67].

Figure 3

Asymmetric, unidirectional releasing microdevices. (a) Schematic flow diagram depicting the sequential layer by layer photolithographic process, (b) Optical micrograph of drug-hydrogel loaded devices, (c) Fluorescent micrograph showing multiple model drugs (DNP-BSA; FITC-BSA; Texas red-BSA) loaded via layer by layer lithography in the same reservoir, and (d) Fluorescent micrograph of combined filters showing the three BSAs loaded in the same microdevice [106].

Figure 4

Bioadhesive PMMA microdevices fabricated using photolithography and reactive ion etching. Optical micrograph of (a) single [43] and (b) multi-reservoir fabricated microdevices [108], (c) fluorescent micrograph showing the presence of covalently bound avidin-FITC as a model for introducing targeting proteins to device surfaces [109], and (d) microdevices containing microposts for the physical introduction of bioadhesive property [110].

Figure 5

(a) A design of a degradable polymer micro-chip device made up of conical reservoirs coated with degradable membranes, each loaded with a specific drug. The top and bottom images show the device in its pre-release and release state respectively. (b) Schematic cumulative release of radio labeled model molecules from devices coated with different PLGA membrane types (x, y, z are ratios of lactic acid to glycolic acid).

Figure 6

(a) Time lapse image sequence of 500 μm self assembling microcontainers being loaded with glass beads. (b) A self-loaded microcontainer overfilled with 150 μm beads [121].