The process of drug delivery still remains an important challenge in drug therapy. An ideal drug delivery system should deliver a drug at the right amount, right place and right time dictated by the needs of the body. Although, current novel drug delivery systems can significantly enhance the therapeutic effect of a drug, as compared to conventional dosage forms, there are challenges and unsolved issues associated with these delivery systems. These include non-specific targeting, toxicity due to chronic exposure, failure of ideal drug release profile, limitations of protein and peptide delivery and poor bioavailability.
In the recent years, MEMS based drug delivery devices have led to the development of novel advanced drug delivery microsystems. Research on MEMS based drug delivery devices or devices for biological or biochemical applications (BioMEMS) have established that they enable tailored drug delivery that is needed for the optimum therapeutic activity of a drug.
MEMS
MEMS are tiny mechanical devices that are built onto semiconductor chips and are generally in micrometres size scales. At nanometres sizes, they are called NEMS. MEMS/ NEMS are the integration of mechanical elements, sensors, actuators and electrical components on common silicon substrate. Other materials such as polymers and ceramics have been used recently, especially in drug delivery devices because of their desirable properties (biocompatibility and biodegradability).
MEMS/NEMS based drug delivery devices: In the integrated circuit (IC) industries, MEMS have revolutionized our world over the past three decades in producing various functional devices on the micron scale. In medicine, while MEMS technology's initial focus is on the development of miniaturized diagnostic tools like biosensors, more recent advances have focused on the development of MEMS devices for drug delivery.
Although still in its infancy, the MEMS based drug delivery devices have already demonstrated immense potential for surmounting challenges associated with conventional controlled drug delivery systems. The main approach utilizes microfabrication technology to develop MEMS/NEMS devices that are capable of releasing drug in response to stimuli and in accordance with preprogrammed release design. These types of devices not only achieve programmable drug delivery, but also provide simultaneous non-invasive monitoring of both drugs and devices. Advances in microfabrication technology have made entirely new types of drug delivery micro devices possible.
MEMS delivery devices promise to usher in an era of miniaturization. MEMS delivery devices have a number of advantages. They are:
■ Miniaturization of a device is ideal for implant and need less than a microlitre of a drug for analysis and operation.
■ Simplicity of release mechanism
■ Convenient and accurate for dosing
■ Faster drug delivery with fewer side effects
■ Potential for local delivery
■ Stability enhancement
■ Ability to store and release multiple drugs on demand
Some examples of therapeutic applications of MEMS include implantable microchips for pulsatile delivery, microneedle arrays for transdermal and cellular delivery, water-powered MEMS osmotic pump, nanoporous bio-capsules for cell encapsulation and sustained delivery and electronic or biodegradable MEMS for controlled drug delivery. In addition, recent developments in polymeric MEMS for drug delivery include the resorbable polymeric MEMS for drug delivery and biodegradable microneedle transdermal patches.
Two important microfabricated systems
Implantable microchip: It is a typical MEMS microchip and is based on multiple micro reservoirs into a substrate (usually silicon) that contain individual doses of drugs either in a solid, liquid or gel form. Each reservoir is capped with conductive membrane (e.g. gold) and is controlled by a microprocessor. Each dose is released by the electrochemical dissolution of the gold membrane. A microchip, as small as 2 mm by 2 mm, can accommodate over 1000 reservoirs. The first development of a microchip with application in drug delivery by researchers at the MIT, US, was reported in Nature (Santini et al., Nature, 397, 335-38, 1999). In 2006, the same researchers demonstrated for the first time used an implant of postage stamp-sized microchips containing 100 tiny reservoirs of medicine and wireless technology, to actively control the release of drugs at different intervals and amounts in dogs for up to six months. This device is currently being developed by MicroCHIPS Inc. Current developments on microchip systems consists of designing biodegradable polymeric microchip device, which once implanted for drug delivery applications need not be removed.
Microneedles: Conventional transdermal delivery is severely hindered by the inability of most drugs to enter the skin at therapeutically useful concentrations because of impermeability of the barrier dead tissue called stratum corneum. Microneedles are long enough to penetrate across the stratum corneum, but short enough not to stimulate the nerves in the deeper tissue. Hence, microneedles has the potential to dramatically increase transdermal delivery of many drugs, especially for macromolecules. By adapting microfabrication technology, small arrays of solid and hollow silicon microneedles can be made. These arrays are usually 150 microns long, tapering from a base of 80 microns to a point less than 1 micron. The ALZA Corp. has commercialized a microneedle - TD patch - (Macroflux) that uses a thin titanium screen that consists of 200 microns microneedles. Additionally, microneedles are capable of painless delivery of drugs into cells and tissues.
Future prospects: Today MEMS/NEMS based drug delivery devices have become commercially feasible due to convergence of technologies and regulatory accommodation. Microneedles has been demonstrated as powerful tool for delivery of drugs and macromolecules with no pain, which was impossible for traditional methods. Various research works have been shown that future drug delivery micro-devices will enable the creation of novel systems that can be tailored to give any delivery profile desired. It must be noted that several microfabricated devices are still in development stage, albeit many technologies are patented. However, many of the devices, termed by experts as generation next devices, are getting closer to practical applications. It is foreseeable that, some day, drug delivery microchips could be multifunctional with sensors that not only programmed to release needed doses precisely at the right time but also monitor non-compliant patients and patient location via global positioning satellite.
(The author is reader in pharmacy, Annamalai University, Annmalainagar)