Elsevier

Advanced Drug Delivery Reviews

Volume 55, Issue 3, 24 February 2003, Pages 315-328
Advanced Drug Delivery Reviews

Microfabricated drug delivery systems: from particles to pores

https://doi.org/10.1016/S0169-409X(02)00227-2Get rights and content

Abstract

Microfabrication techniques which permit the creation of therapeutic delivery systems that possess a combination of structural, mechanical, and perhaps electronic features may surmount challenges associated with conventional delivery of therapy. In this review, delivery concepts are presented which capitalize on the strengths of microfabrication. Possible applications include micromachined silicon membranes to create implantable biocapsules for the immunoisolation of pancreatic islet cells—as a possible treatment for diabetes—and sustained release of injectable drugs needed over long time periods. Asymmetrical, drug-loaded microfabricated particles with specific ligands linked to the surface are proposed for improving oral bioavailability of peptide (and perhaps protein) drugs. In addition, microfabricated drug delivery systems ranging from transdermal microneedles to implantable microchips will be discussed.

Introduction

The application of micro- and nanotechnology to the biomedical arena has tremendous potential in terms of developing new diagnostic and therapeutic modalities. Over the last several years, microfabrication technology has been applied to the successful development of a variety of health care-related products including diagnostic (‘lab-on-a-chip’) systems and techniques and apparatus for high throughput screening of new drug candidates [1], [2]. While the majority of research has focused on the development of miniaturized diagnostic tools, researchers have more recently concentrated on the development of microdevices for therapeutic applications. Micro- and nanofabrication techniques are currently being used to develop implants that can record from, sense, stimulate, and deliver to biological systems. Micromachined neural prostheses, drug delivery micropumps, tissue scaffolds, and stents [3], [4], [5], [6] have all been fabricated using precision-based microtechnologies. Drug delivery remains an important challenge in medicine [7] and microfabrication techniques may be used to develop novel drug delivery devices with capabilities not possible with current systems. This paper will review some of the current and future approaches that utilize microfabrication technology for drug delivery.

Section snippets

Controlled release drug delivery systems

Conventional dosage forms, such as oral delivery and injection, are the predominant routes for drug administration. However, these types of dosages are not easily able to control the rate of drug delivery or the target area of the drug and are often associated with an immediate or rapid drug release. Consequently, the initial concentration of the drug in the body peaks above the level of toxicity and then gradually diminishes over time to an ineffective level. The duration of therapeutic

Microfabrication technology

The use of traditional microfabrication techniques, the same processing techniques used to manufacture microelectronic chips, is a recent and alternative method of creating drug delivery platforms. Microelectronic process engineering was a discipline that developed due to the rapid growth of the integrated circuit industry. Traditionally, microelectromechanical systems (MEMS) research has been used to produce functional devices on the micron scale, such as sensors, switches, filters, and gears,

Microneedles for transdermal drug delivery

One alternative to oral delivery and intravenous injection is the administration of drugs across the skin. This approach seeks to avoid any degradation of the molecules in the gastrointestinal tract and first-pass effects of the liver associated with oral drug delivery as well as the pain of intravenous injection [10], [11], [12], [13], [14]. It also offers the possibility to continuously control the delivery rate over extended periods of time [14]. However, conventional transdermal drug

Implanted microchip for localized drug delivery

Microfabrication technology has also created a new class of controlled release systems for drug delivery based on programmable devices. These devices are particularly intriguing due to their small size, potential for integration with microelectronics and their ability to store and release chemicals on demand [18]. With the recent advancements in biosensors and micromachining, implanted responsive drug release systems are becoming more plausible.

Bioadhesive microparticles for oral drug delivery

Oral drug delivery is one of the most preferred methods of drug administration due to its non-invasive nature. However, it is generally not a viable method for peptide and protein delivery. The human GI tract resists absorption of peptides, proteins, and other large molecules until they are broken down into smaller molecules. The acidic environment of the stomach combined with an array of enzymes and physical barriers in the intestines either destroy or prevent absorption of nearly all

Nanoporous immunoisolating biocapsules

Diabetes mellitus (DM) represents a serious medical problem. In the US alone, it is the third leading cause of death. While the majority of patients have type 2 diabetes, about 10% of all patients diagnosed with DM are insulin-dependent (type 1). In both cases, disease is caused by decreased circulating concentrations of insulin and decreased response of peripheral tissue to insulin (insulin resistance) [33]. The disease manifests itself as hyperglycemia. Insulin remains the mainstay of

Conclusions

The race to find effective diagnostic and therapeutic tools is under way, as scientific and engineering disciplines uncover and elucidate more about the human pathologic condition than ever before. Although we are getting closer to the clinical application of intelligent drug delivery devices, many challenges remain for the future. The convergence of microtechnology and biology will lead to new approaches in drug delivery and may provide advantages over existing technologies. By focusing

Acknowledgements

Funding is gratefully acknowledged from The Whitaker Foundation, NSF ECS9820829, NSF Career, and iMEDD, Inc. Also, special thanks to those who have contributed to this work: Lara Leoni, Mike Lubeley, Chris Bonner, and Aamer Ahmed of UIC; colleagues from iMEDD, Inc.; and Professors Derek Hansford and Mauro Ferrari from OSU.

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