Authors: Sarah A. Stewart, Juan Domínguez-Robles, Ryan F. Donnelly, and Eneko Larrañeta
Published online 2018 Dec 1
“A promising alternative delivery method is the use of polymeric implantable devices to deliver drug compounds. Implantable drug delivery systems allow targeted and localised drug delivery and may achieve a therapeutic effect with lower concentrations of drug [3,5,6]. As a result, they may minimise potential side-effects of therapy, while offering the opportunity for increased patient compliance [7]. This type of system also has the potential to deliver drugs which would normally be unsuitable orally [6], because it avoids first pass metabolism and chemical degradation in the stomach and intestine, thus, increasing bioavailability [7]. Implantable devices will require a healthcare professional for insertion, and the insertion itself will be a relatively invasive process. However, unlike other methods this will only be required once. The prolonged drug delivery that will be achieved without the reliance on patient compliance overcomes these disadvantages. Another advantage of implantable drug delivery devices is that they offer the opportunity for early removal if adverse effects require termination of treatment [8,9].
Implantable drug delivery device classification is not a straightforward task as there are a number of complex implants that will fall into hybrid categories. Nevertheless, implantable drug delivery devices can be broadly classified in two main groups: passive implants and active implants. The first group includes two main types of implants: biodegradable and non-biodegradable implants. On the other hand, active systems rely on energy dependent methods that provide the driving force to control drug release. The second group includes devices such as osmotic pressure gradients and electromechanical drives. However, the latter are normally metallic implants and this review focuses on polymeric devices. Consequently, they will not be covered in this review.
Mechanisms of drug release from implantable systems are mainly classified into four groups: matrix degradation; controlled swelling; osmotic pumping; and passive diffusion [19]. For systems based on controlled swelling, solvent penetration into the matrix of the device controls the rate of release. This is usually much slower than diffusion of the drugs, and will, therefore, lead to a lower release rate [15]. Although the diffusion from swollen matrices is mainly responsible for the drug release, matrix degradation could also contribute in the effectiveness of these systems [20].
On the other hand, osmotic pumping and passive diffusion mechanisms of drug delivery are the most promising for linear delivery of drugs. In this case, the amount of released drug is proportional to the square root of the release time.
A number of factors need to be considered when choosing a manufacturing method for production of an implantable drug delivery devices including: cost, efficiency and differences in properties of the produced implants. Implants can be manufactured using a variety of techniques including: compression, solvent casting, hot melt extrusion, injection moulding or more recently 3D printing. Thermoplastic polymers such as PLA or PLGA can produce implants using techniques such as: hot moulding, injection moulding, compression or extrusion [7]. Implants prepared by different techniques are unlikely to form polymers with exactly the same microporous structure and will degrade at different rates and, therefore, will have different in vitro and in vivo release profiles [7]. Fialho et al. compared the process of hot moulding and compression as techniques to make intra-ocular implants, and found that, the manufacturing technique significantly influenced the polymer degradation and, therefore, drug release from the resulting implants [7], with compressed implants showing an increased rate of drug release than their moulded counterparts.
The market for polymeric implantable drug delivery devices is one that is growing. The advantages that this delivery route demonstrate over more conventional drug delivery methods, such as oral tablets, make it likely that it will continue to grow and that the number of implantable drug delivery devices on the market will increase. However, implantable drug delivery devices have a number of disadvantages including the invasive nature of this delivery method. The advantages that these devices can offer with respect to patient compliance, stability of drugs within these devices and removability if adverse reactions occur, outweigh these disadvantages that exist. Current therapeutic applications of implantable drug delivery devices are covered in this article. However, the use of implantable drug delivery devices has the potential to span far greater than these conditions mentioned. One such condition where these devices could have a major impact is in the treatment or prevention of human immunodeficiency disease (HIV). 3D printing offers an interesting prospect as an exciting new manufacturing method, one which provides a unique opportunity to produce complicated designs or personalised implantable devices. However, when compared to more traditional methods of implantable device manufacture, such as hotmelt extrusion or compression moulding, this manufacturing method comes with additional scale up and regulatory challenges. The FDA approval of the first 3D printed tablet in 2015 makes the reality of 3D printing as a pharmaceutical manufacturing method much more likely”(Stewart et al., 2018).
Drug delivery methods have been advancing for a while and many have been successful. Some of the more recent advances are in diffusion implants for birth control. While there are two types of implants, passive and active, the birth control passive implant in the arm has been celebrated for its effectiveness. If works for birth control what else can it work for? New technology has been developing for cancer treatments and ocular conditions. Could this tech be converted for a diffusion drug release of anti-seizure medication. Epileptic patents could benefit from an arm or body implant that they do not have to think about or worry about having on their person at all times. The injection or pill methods of medication are subject to human or situational error. If the drug is diffusing or active releasing in the body when a seizure is sensed, the worry would disappear. The advancements of this type of revulsion are technology is hopeful for the chronically ill. Wishes for a better quality of life and more enjoyable future will always bring motivation to research.
One concern for this type of new emerging technology is the safety. Putting a device inside one’s body is already majorly invasive. Then adding the drug component. Drugs are powerful and dangerous if administered incorrectly. It can be nerve wracking for the epileptic community to switch anything that has to do with medication because there is a risk of seizures to return. Seizures can cause life altering damage to the body so these concerns should not be taken lightly.
Reference
Stewart, S. A., Domínguez-Robles, J., Donnelly, R. F., & Larrañeta, E. (2018). Implantable polymeric drug delivery devices: Classification, manufacture, materials, and clinical applications. Polymers, 10(12), 1379. https://doi.org/10.3390/polym10121379
