Drug delivery is about improving the efficacy and safety of therapeutics by getting the right dose of the right drug to the right place at the right rate and time. Approaches to drug delivery have existed for many hundreds of years; Egyptian physicians created oral tablets and ointments, and physicians began to use intravenous delivery after the circulatory system was first described in 1657. Controlled release technologies date back to the mid-1900s. [1]
The benefits of using a drug delivery system include: [1, 2]
• delivery over long periods
• greater patient convenience
• delivery of otherwise hard-to-formulate drugs, such as large biomolecules, poorly water-soluble drugs, or drugs with a narrow therapeutic window
• delivering drugs across physiological barriers, for example the skin, blood-brain barrier and blood-retinal barrier
• localized delivery reducing systemic toxicity and allowing lower doses of drugs.
The challenges that drug delivery development faces include: [1-3]
• incorporating and controlling complex dosing schedules or personalised dosing into a delivery system
• dealing with variable drug responses triggered by periodic biological fluctuations
• delivering multi-drug regimens
• keeping drugs stable while held in the delivery system.
Drug delivery systems range from gels and patches, through microspheres and nanoparticles, to complex devices such as external or implanted pumps and microelectromechanical systems (MEMS).
An introduction to microelectromechanical systems
MEMS are small, integrated devices that combine electrical and mechanical components, and have been made possible by the advances in microfluidics and electronics miniaturisation. These range from simple systems with no moving parts to highly complex systems. MEMS can be aseptically manufactured using biocompatible materials, and they can be hermetically sealed. MEMS drug delivery devices generally consist of three components: drug chamber, drug release mechanism and packaging, and may incorporate sensors, channels, pumps, valves, needles, membranes and single or multiple drug reservoirs. [1-5]
MEMS devices can be implantable or wearable, and have applications in chronic and long-term disease. They can deliver drugs to specific locations, and some can deliver more than one drug. Those with integrated sensors can tailor delivery rates to the patient's needs based on detection of vital signs or biomarkers. [1, 5, 6]
MEMS are small and lightweight and can easily be integrated with electrical and electronic circuits. MEMS devices can be powered or non-powered. Powered MEMS have low power consumption, and may be self-powered. MEMS devices do have a number of downsides, however. They can be fragile, and may fail as a result of contamination, fatigue, friction or wear. [5]
Non-powered MEMS drug delivery
Non-powered MEMS devices can be smaller than powered devices as they need no power supply. Their delivery rate can be modified by the use of different materials or drug formulation, and by the environmental properties at the delivery site. They may have low release rates, however, and only respond slowly to external stimuli. The delivery rate cannot generally be changed or stopped after administration. Non-powered approaches include passive diffusion devices, osmotic pressure, hydrogels and microneedles. [1]
Powered MEMS drug delivery
Powered MEMS devices are more complex and are often larger than non-powered devices, but they have higher release rates, faster responses and can be controlled externally. The micropumps may be electromagnetic, piezoelectric, electrostatic, thermopneumatic, bimetallic, electrochemical or employ a thermal/shape memory alloy, among other approaches. [1]
Powered drug delivery devices allow physicians to tailor drug delivery precisely through real-time monitoring and physical sensors. As an example, an external pancreas combining an insulin pump with continuous glucose monitoring can be programmed and monitored externally via a smartphone or tablet. [1]
MEMS applications: Drug delivery to the brain
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