biodegradable constant pain relief
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A BIODEGRADABLE IMPLANT FOR CONSTANT PAIN RELIEF FOLLOWING SURGICAL PROCEDURESFinal Paper-BME 3700Due Date: April 28, 2016Group Members: Derek Dodge, Celine Agnes, Ashley Vanaman, Kristen Campbell and Daniel Evans
AbstractPain relief drugs are a ubiquitous method of comfort after major surgeries. Many of the current methods of delivery, like orally taken pills and constant intravenous delivery, have significant drawbacks. Though the drawbacks vary from method to method, they all stand to be improved. The idea of an implantable, biodegradable capsule that constantly releases medication would solve many of these issues. It is a physically feasible idea that can be made with existing technology and techniques, and would be more effective at treating pain than current methods. While the device is untested as of now, it is hoped that in vitro and in vivo tests would be possible in the near future. Several tests that could be run are described below. In addition, possible modifications and future additions to the design are also listed.
IntroductionIn the modern medical community today, there is a constant need to improve the field of surgery and discover new ways to make the surgical procedures more successful and faster. With this constant improvement of the surgical field, there lacks improvements in the area of pain relief post surgery. The product that the group of students is looking to develop in this project does not currently have anything quite like it. In the medical society, there is a critical and consistent need for pain relief drugs.There are currently four different ways of controlling pain relief post surgery. The first of these is the Intravenous Patient Controlled Analgesia. This is a pump that allows the patient to push a button and the machine then pumps a small amount of pain medicine into the IV line in your arm. This is a typical and innovative method due to the fact that it provides stable pain relief and a sense of control over their pain management. As long as family members are not in control of the button, the dosage of the medication is limited into a safe amount. The second of these is the Patient Controlled Epidural Analgesia. The epidural uses a PCA pump to deliver the medicine. The way this method is done is by inserting an epidural catheter through the patient's back. This could be a cause for concern in the sense of discomfort for the patient. It is also not a risk free procedure for pain control. The epidural does not always adequately control pain. The third of these is the Nerve Blocks. The Nerve Blocks have a more specialized capability to control pain in a small area of the body. This can allow for the amount of medication to be more reduced. This can help to prevent possible addictions to medication. Finally the most common method of pain medication delivery is pain medications taken by mouth. These are ordered by the doctor and must be taken at certain intervals throughout the day. Though this gives the user a lot of control in the medication and pain relief, it also comes with many disadvantages. These disadvantages include addiction, patient responsibility, and even overdose.It can be seen from the disadvantages discussed above, there are definitive issues facing the current model of delivery, many having to do with user error. A patient is often unfamiliar with the pills being given to them, and can possibly give incorrect doses to themselves resulting in more pain than is necessary. This disadvantage can be eliminated by removing the aspect of self control from the method of delivery.
Figure 1: Traditional oral drug delivery versus a constant method, like is suggested. The line with the multiple peaks is the traditional method and often leads to levels of drug past what is safe or below what is necessary to provide relief. The constant release never crosses the toxicity line or subtherapeutic line. 
By having a drug that has a zero-order controlled release, the drug concentration is kept constant within the therapeutic level. This will eliminate the patient from becoming addicted where they can potentially overdose and do more damage to their bodies than intended. Another issue is other people besides the patient taking the pills or the pills being sold. This can obviously negatively affect other individuals besides the patient. That also ties into the next issue. Pills tend to have more addictions associated with them than other forms of pain medication. This is mainly due to the easily abused nature of their ingestion. It is difficult for a doctor to limit the amount taken once the patient has left the hospital or wants to abuse the drug. The group of students carefully discussed these disadvantages as a way to design a proposed solution that meets the needs and improves the disadvantages.The proposed solution to these disadvantages and need for a more efficient way of delivering pain medication is a degradable capsule to be filled with drugs and implanted during surgery. It would be multilayered and as each layer degrades, a constant release of pain medication is maintained. This would help in limiting the inconsistency of drug dosage associated with pills as it spikes and falls over preferred levels. There would also be no time delay for pain relief as the medication is constantly being given, and the patient does not have to worry about constantly timing their pills and the waiting period before the medication kicks in. There is also no way for a patient to sell or overuse the drug.
DesignThis capsule would be made from an easily degradable polymer. The first choice material would be a polyanhydride. It is a copolymer of the aliphatic and aromatic polymers PCPP and sebacic acid. The aromatic degrades over years, while the aliphatic degrades within days. By combining them, it is possible to create a customizable degradation time, based on the patients needs. The window available is anywhere between those two extremes. It also degrades in a in layers, which is perfect for the groups purposes. When it does degrade, it breaks down into compounds easily dealt with by the body. It can already be produced in wafer form, so it would be a simple modification to produce a multi-laminar vesicle, or a set of hollow, roughly spherical shells imbedded within each other. 
Figure 2: The chemical formula for the polyanhydride suggested. 
The first possible method of production would be where the multi-layered shell would be formed first. Then the empty capsule would be loaded with the drug after the fact. This could be difficult as the layers have to be resistant to the drugs passage through to prevent early release. Making them one way acceptors of the drugs could be very difficult. A more reasonable solution could be making the capsule one layer at a time. As each one is made, it could be loaded with the drug. This would eliminate the need for the drugs to pass through the layers. Both of these polymers would be assembled by the layer by layer method.
Figure 3: A simplified example of the layer-by-layer method. A substrate is used as a base for the polyanhydride to bind to. The drug would be on top of the polymer, then more layers of polymer would be added on top, alternating each layer. 
However loading each individual layer is very time consuming and difficult. The best overall option is likely simply binding the drug to the polymer itself. As the polymer degrades, it cannot hold the drug anymore and it is released into the body at a very regular rate. This also does not need a specific shape, specifically the shells do not need to be uniform and implanted within themselves. As long as the polymer is made at the correct porosity to allow the drug to be attached uniformly throughout, it does not matter the internal structure. The polymer will still break down in layers regardless.In regards to size of the capsule, there are many factors to consider. The severity of the procedure is one of the most major concerns. Larger capsules with more drugs are required for more painful surgeries. The abdomen can also allow for such larger capsules, so a longer drug delivery period is possible. If the time period necessary is so long that even increasing the size and aromatic ratio is no longer viable, it could be a minor outpatient procedure to implant another. It also would not have to be removed, as the body will dispose of it itself, with no further surgeries unless more drugs are required. The location within the body, however, is not a major concern. It can be placed in the abdomen, regardless of what the procedure was. A relatively small incision can be used to insert a capsule, separate from the initial surgery if the main incisions were on the extremities. As long as the drug has access to the blood, it can spread to where it is needed.The implant also has to be able to bind to multiple kinds of pain relief medications. Many people are incapable of taking certain kinds of medication due to allergies or types of illnesses. Every drug is also not able to bind to every type of functional group in a polymer. The functional groups on the polymer may have to be modified depending on the drug being applied.
TestingMore than 50 million people in the United States have allergies. Allergy testing, specifically skin testing, is a convenient and accurate way to find effective treatment. The first type of skin test includes a drop of a suspected allergen pricked or scratched on the surface of the skin of the back or forearm. The second type of skin test involves a small amount of the suspected allergen injected into the skin of the arm or forearm. Redness and swelling at the test spot represents an allergy and multiple suspected allergens can be tested at once. Skin allergy testing would be ideal for the polyanhydride used in this biomedical device because it is fast, with reactions usually appear