The oral route is predominantly the most convenient method of drug delivery. However, all drugs cannot be delivered via the same route as they might lose their efficacy. One of the recent advancements in the delivery of sensitive drugs has been the use of polymer-based implants.
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Conventional Drug Delivery System
Although the oral route is the most popular method of drug delivery, many drugs are not suitable for this system. This is because drugs might degrade in the stomach (acidic conditions) or intestine (alkaline conditions). Also, many of the newly discovered drugs contain chemicals that are not ideal for oral delivery. Other common methods of drug delivery include transdermal, and intravenous (IV) injection.
The IV method overcomes some of the shortcomings of the oral delivery, such as poor solubility and degradation in the stomach and intestine. Despite this, the IV method has certain challenges. For instance, as it is invasive, it always requires a skilled person for administration.
The transdermal method is non-invasive but only a few drugs can possess the specific properties required, such as a Log P value between 1 and 3, low molecular weight, highly soluble, and high partition coefficient, to pass through the outer skin barrier.
Implantable Drug Delivery System
Scientists have developed an alternative method of drug delivery by using polymeric implantable devices to deliver drug compounds. An implant is a single unit drug, which is designed meticulously to deliver a drug compound at a therapeutically desired rate over a prolonged period. This system of drug delivery is targeted and localized and, thereby, therapeutic effects are realized at a lower drug concentration. This process minimizes the potential side effects of the drug with maximum effectiveness.
Importantly, this method of drug delivery is suitable for drug compounds that cannot be introduced via the oral route. Although it is an invasive method requiring skilled personnel for inserting the implantable device, it is a one-time procedure. These implants are inserted subcutaneously in the body for the continuous release of drugs for an extended period. Also, implantable drug delivery devices could be removed immediately if a patient experiences adverse effects from the treatment.
Role of Implantable Polymeric Drug Delivery Device
Implantable polymeric drug delivery device has been broadly classified into two groups, namely, active implants and passive implants. These are briefly described below:
Active Implants
Active implants are energy-dependent methods. They require energy as a driving force to control drug delivery. The majority of the active implants are electronic systems that are developed using metallic materials.
Passive Implants
Passive implants are based on osmotic pressure gradients and electromechanical drives for drug release. In this method, the drugs are packed within a biocompatible polymer molecule. These are of two types, i.e., biodegradable and non-biodegradable implants.
Non-biodegradable and Biodegradable Implants
Non-biodegradable implants are commonly prepared using polymers such as poly(acrylates), silicones, poly(urethanes), or copolymers, e.g., poly(ethylene vinyl acetate). These devices could be either monolithic or reservoir types. Monolithic implants are developed using a polymer matrix where the drugs are homogeneously dispersed. The reservoir-type implants comprise a compact drug core that is covered by a permeable non-biodegradable membrane. The thickness of the membrane and its permeability determines the release kinetics. Non-biodegradable devices are structurally resilient and robust over their lifetime. However, one drawback associated with this device is that when the drug depletes, the device has to be removed.
Biodegradable implants are developed using polymers or copolymers, e.g., poly(caprolactone) (PCL), poly(lactic acid) (PLA), poly(lactic-co-glycolic acid) (PLGA), etc. These polymers are naturally broken down into smaller fragments over time and, subsequently, excreted or absorbed by the body. The degradable kinetics of the polymers is thoroughly studied such that the rate of drug release could be adjusted precisely. The main advantage of this type of implant is that does not require an extraction procedure at the end of the treatment. These biodegradable implants are also available as monolithic and reservoir implants.
Brief Overview of the Mechanism of Drug Release from Implants
Various mechanisms of drug release are associated with implantable systems such as matrix degradation, osmotic pumping, chemically controlled, controlled swelling, and passive diffusion. The controlled swelling-based mechanism involves the slower release of drugs compared to implant devices based on passive diffusion. Linear release of drugs relies on both osmotic pumping and passive diffusion mechanisms of drug delivery.
When a drug release system is based on mechanisms such as swelling, osmotic pressure, or passive diffusion, the release kinetics of the drug compound is dependent on several factors such as diffusion coefficient of the molecule in the polymer, the solubility, the amount of drug load, and the in vivo degradation rate of the polymer
Advantages and Disadvantage of Implant Drug Delivery System
The main advantage of an implant drug delivery system is controlled drug release at the targeted site, which helps minimize the risks of toxicity and reduce dosing frequency. It also increases patient compliance because this method of drug administration is largely independent of the patient's input. Additionally, an externally programmed pump facilitates intermittent drug release which is extremely beneficial in several therapeutic approaches.
Another interesting property of this mode of drug delivery is the capability to release drugs in response to external or biological stimuli. The polymeric material provides flexibility in respect to the amount of drug-loaded and released.
This system of drug delivery has certain disadvantages that include its invasive method, the danger of failure of drug delivery, the need to be terminated externally, and expensive treatment. Also, this system of drug delivery is limited to potent drugs and the biocompatibility factor must be considered.
Clinical Application of Implantable Drug Delivery System
Recently, researchers have developed Implantable drug delivery devices for glaucoma management. This system has also been used in the treatment of cancer, ocular disease, osteoporosis, contraception, narcotic antagonists, and many other treatments.
Sources:
- Stuart, A. (2021) The Promise of Implantable Drug Delivery Systems. [Online] Available at: www.aao.org/.../promise-of-implantable-drug-delivery-systems
- Stewart, S. A. et al. (2018) Implantable Polymeric Drug Delivery Devices: Classification, Manufacture, Materials, and Clinical Applications. Polymers, 10(12), pp. 1379. https://doi.org/10.3390/polym10121379
- Manickavasagam, D. and Oyewumi, O.M. (2013) Critical Assessment of Implantable Drug Delivery Devices in Glaucoma Management. Journal of Drug Delivery. 895013. pp. 12 pages. https://doi.org/10.1155/2013/895013
- Blackshear, P.J. (1979) Implantable drug-delivery systems. Scientific American. 241(6). pp. 66-73. doi: 10.1038/scientificamerican1279-66. PMID: 504981.
Further Reading