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== Manufacturing ==
== Manufacturing ==
Polymer microneedles can be manufactured in a variety of different ways. Most microneedles are manufactured through micromolding, which is a fairly simple process. However, a master structure must be created first. The most common method is described below
Most microneedles are manufactured through micromolding, which is similar to traditional {{wp|injection molding}}. This process lends itself well to mass production. However, a master structure must first be created to provide a mold.
 
Microneedle master structures are usually produced through {{wp|photolithography}}. First a substrate, usually glass or silicon, is coated with an etch-resistant such as chromium or silicon nitride. This can be done through a variety of methods such as sputtering or chemical vapour deposition. 


===The Integrated Lens Technique===
===The Integrated Lens Technique===

Revision as of 20:28, 28 November 2008

Template:MECH370 Polymer microneedles are micron-scale needles, usually in an array, in development for transdermal drug delivery and controlled-release.

Overview

The development of more advanced drugs has created the need for a more advanced way to administer them. DNA- and protein-based compounds cannot be administered orally (since they break down in the stomach before they can be absorbed), and hypodermic needles are fairly painful and invasive. This has led to transdermal drug delivery as an attractive solution. The problem faced by most W is the low W of skin. Skin permeability can be increased through the use of drugs and ultrasound although the results are limited. Microneedles have been shown to greatly increase the skin's permeability, allowing for an effective transfer of drugs.[1]

Typically, microneedles tips have a radius of curvature of less than 1 um for piercing of the skin. The are approximately 150 um long. The entire length does not pierce the skin since the surface of the skin is not flat - due to hair and W. The microneedles penetrate deep enough to pass the first ~15 um of skin, the barrier known as the W. However, they do not penetrate deep enough to touch nerves. The length can be modified as needed [1].

In the past, microneedles have been made from metal, silicon, and glass[2]. Today, some very promising technology is focused on polymers since they are biocompatable, biodegradable, and easy to manufacture. They also degrade rapidly in the body, providing a drug distribution method and eliminating the risk of the needles fracturing and becoming embedded in the skin.

Types of Microneedles

Polymer microneedles are fabricated in a variety of shapes and sizes depending on the specific application. Solid microneedles are used in order to pierce the skin, increasing permeability. A patch containing the required compound can then be administered or the compound can be placed directly on the needles. Hollow microneedles can be made to encapsulate a drug for either rapid-release or controlled-release.

Manufacturing

Most microneedles are manufactured through micromolding, which is similar to traditional W. This process lends itself well to mass production. However, a master structure must first be created to provide a mold.

Microneedle master structures are usually produced through W. First a substrate, usually glass or silicon, is coated with an etch-resistant such as chromium or silicon nitride. This can be done through a variety of methods such as sputtering or chemical vapour deposition.

The Integrated Lens Technique

  1. A layer of chromium is deposited onto a glass substrate and a positive W is coated onto the chromium layer.
  2. A photomask with pattered holes of the required dimension and spacing is placed on the photoresist.
  3. The photoresist is exposed to UV light through the W.
  4. The photomask is removed by soaking in a photographic developer, leaving behind the photoresist and unprotected chrome of the desired array.
  5. The revealed chrome layer is etched using a chrome etchant.
  6. The back side of the glass is coated with photoresist to protect it from etching.
  7. Wet chemical etching is used in order to create hemispherical depressions on the class - these act as microlenses. The rest of the structure is opaque due to photoresist coating.
  8. A film of SU-8 negative epoxy photoresist is placed on the glass substrate – including within the microlenses.
  9. This compound is soft-baked for 12 hours at 100°C
  10. The film is exposed to UV light from the bottom through the microlenses. This focuses the light into a conical path leaving a latent image of the microneedle in the epoxy.
  11. The compound is baked once more for 30 minutes at 100°C, crosslinking the photo-exposed SU-8.
  12. The non-crosslinked SU-8 is developed away with a photo developer, leaving behind an array of microneedles.

Next, polydimethylsiloxane (PDMS) is poured over the master structure to create a negative mold. The cured PDMS mold is filled with biocompatible polymer pellets. The pellets are melted and after cooling the polymer microneedles are removed from the mold. [3]

Although the PDMS molding is rather quick and efficient, the master structure takes time to produce and can become complex for hollow needles. The mold can be reused, but often break during removal of the polymer array.

Improving Efficiency

One way to improve the efficiency of microneedle manufacturing is to remove the master structure fabrication step entirely. It is the step that takes the longest and requires very specific laboratory conditions. This can be done through photon polymerization.

Photon Induced Polymerization

Currently, photon polymerization has limited biocompatibility and biodegradability, however many studies are being done to further this technology. The materials fall under the name Ormocer and are hybrid organic-inorganic. However, they have been found to be non-toxic and biologically inert [4]. The photon polymerization method is described below:

Appropriate Applications

If further developed, polymer microneedles could prove useful for W and W in developing countries. The patches are small, portable and could be administered by someone with little or even no medical training. [5]

References

  1. 1.0 1.1 Sebastien Henry, Devin V. McAllister, Mark G. Allen, Mark R. Prausnitz, Microfabricated microneedles: A novel approach to transdermal drug delivery, Journal of Pharmaceutical Sciences, vol.87, no.8, 1998.
  2. Devin V. McAllister, Ping M. Wang, Shawn P. Davis, Jung-Hwan Park, Paul J. Canatella, Mark G. Allen, Mark R. Prausnitz, Microfabricated Needles for Transdermal Delivery of Macromolecules and Nanoparticles: Fabrication Methods and Transport Studies,Proceedings of the National Academy of Sciences of the United States of America, Vol. 100, No. 24, 2003.
  3. Jung-Hwan Park, Yong-Kyu Yoon, Seong-O Choi, Mark R. Prausnitz, and Mark G. Allen, Tapered Conical Polymer Microneedles Fabricated Using an Integrated Lens Technique for Transdermal Drug Delivery, IEEE Transactions on Biomedical Engineering, vol. 54, no. 5, 2007.
  4. A. Doraiswamy, C. Jin, R.J. Narayan, P. Mageswaran, P. Mente, R. Modi, R. Auyeung, D.B. Chrisey, A. Ovsianikov, B. Chichkov, Two photon induced polymerization of organic–inorganic hybrid biomaterials for microstructured medical devices, Acta Biomaterialia,vol. 2, no. 3, 2006.
  5. John Toon, Microneedles: Report describes progress in developing new technology for painless drug and vaccine delivery, gtresearchnews.gatech.edu/newsrelease/needlespnas.htm
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