Key concepts in drug delivery
Applications of drug delivery systems
Commercial relevance
References
Drug delivery utilizes various methods and/or carriers to transport therapeutic agents to the tissue, organ, cell, or subcellular organ of interest for release and absorption. Some of the primary goals of drug delivery systems are to improve the drug's chemical characteristics, increase its pharmacological activity, and/or reduce unwanted side effects.
Since the first drug delivery system was approved for use in the 1950s, various technological advances have allowed for the development of long-term drug delivery through several routes of administration while carrying a wide range of therapeutic agents.1
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Key concepts in drug delivery
What is drug delivery?
Modern pharmaceutical agents can vary significantly in size and chemical complexity, with most therapeutics classified as either small molecules or biologics. Both small-molecule drugs and biotherapeutics are associated with certain limitations in their ability to effectively deliver to the target tissue.
In an effort to overcome these challenges, a diverse range of drug delivery systems has been developed, some of which include liposomes, nanocarriers, and affinity drug conjugates.
The pharmacokinetics of a drug refers to its absorption, distribution, metabolism, and elimination (ADME) properties within the body. Drugs administered intravenously, for example, are immediately absorbed into the bloodstream, whereas most absorption for small-molecule medications occurs in the gastrointestinal tract following oral administration.2
Comparatively, subcutaneous administration of drugs often extends the duration of absorption due to the entry of the drug into the lymphatic system, which can take several hours or days to complete.
Due to their absorption pharmacokinetics, each of these routes of administration has several advantages and disadvantages. For example, although oral drugs are associated with better patient compliance, the harsh environment of the gastrointestinal tract can lead to the degradation of biomacromolecules.
Therefore, encapsulating these therapeutic agents with appropriate drug delivery systems can protect the active agents, thereby improving their oral bioavailability and therapeutic index.
Precision Drug Delivery Systems | Steven Rosenzweig | TEDxCharleston
Learn More Here: Optimizing Drug Delivery Using AI
Applications of drug delivery systems
Chronic disease management
Recent advancements in drug development have allowed patients to live with chronic diseases for much longer than previously possible.
Currently, the most common chronic diseases include hypertension, high cholesterol, arthritis, ischemic heart disease, diabetes, and chronic kidney disease, each of which often requires long-term treatment. As the population continues to age and patients living with these conditions become elderly, the conventional daily prescription may not be practically feasible.
To overcome issues of non-adherence in the management of chronic diseases, various efforts have been made to develop oral long-acting formulations. Long-acting injectable (LAI) formulations, for example, can be administered intramuscularly or subcutaneously to achieve sustained plasma drug concentrations for several weeks or months.3
Likewise, transdermal delivery systems (TDS) are associated with several advantages including long-term systemic or local drug delivery, the ability to bypass first metabolism and uptake by the gastrointestinal tract, as well as continuous delivery.
Various TDS have been developed and tested in different animal species, some of which include gel-based, drug-powder-based, lipidic vesicles-loaded, and nanoparticle-loaded for multiple clinical indications.
Personalized medicine
If it were not for the great variability among individuals, medicine might as well be a science, not an art.”
As compared to traditional approaches to medicine that consider the statistically average patient to be representative of an entire disease, pharmacogenomics considers the genetic variability of each patient to develop personalized therapies.
One approach to personalized medicine involves determining the precise dose, formulation, and drug release kinetics of a medication to fit the specific needs of the patient, as well as the severity and stage of the disease.
Personalized drug delivery systems (PDDS) are defined as solid dosage forms that contain the precise dose of a single or multiple active pharmaceutical ingredient (API) that has been customized for each patient’s unique needs.4
Recently, chewable PDDS have been produced through three-dimensional (3D) printing to treat patients with a rare metabolic disease that allowed for on-demand dosing.
Biologics
In general, biologics are poorly absorbed following oral absorption, which has led many of these therapeutic agents to be administered either intravenously or subcutaneously.
However, even certain classes of biologics can be degraded quickly in the blood, as demonstrated by the degradation of nucleotide- and peptide-backbone biologics that are broken down by nucleases and proteases, respectively.
Nanoscale delivery systems have been developed to overcome these challenges and protect therapeutic agents from these harsh biological molecules to prolong their half-lives while in circulation.
As the number of biologics that have been developed and brought to market continues to rise, the need for long-acting injectable formulations will also increase to ensure patient compliance.
Advanced therapies
One of the most challenging aspects of developing pharmaceutical agents that can be used to treat neurological diseases is the ability of these drugs to pass the blood-brain barrier (BBB).5
To overcome the BBB, various drug delivery systems have been developed, some of which include adeno-associated viral vectors, cell-penetrating peptide-linked nanovehicles, extracellular vesicles, tight junction modulators, and many more.
Nanotechnology, in particular, has been widely explored for its potential to direct the delivery of therapeutic agents into the brain. Biomimetic nanoparticles, which are coated with natural cell membranes like glutathione, for example, have been shown to penetrate the blood-brain barrier successfully.
Likewise, numerous organic nanoparticles, particularly liposomes, solid lipid nanoparticles, and nanoemulsions, have been investigated for their ability to carry gene therapies into the brain to reach glioblastoma tumors.
Although additional safety and efficacy testing is needed, these drug delivery systems have the potential to transform how neurological diseases and cancers are managed to improve patient outcomes.
Discover More: The Global Nanomedicine Market: Key Players and Emerging Technologies in Healthcare
Commercial relevance
Among all nucleic acid therapeutics, messenger ribonucleic acid (mRNA) technologies have garnered considerable attention, particularly when considering their successful incorporation into coronavirus disease 2019 (COVID-19) vaccines.
As of 2021, the global mRNA vaccine market was valued at $47 billion USD, with this market expected to reach $109 billion USD by 2028.6
In addition to Pfizer and Moderna, several other companies are projected to reach similar successes in their development of mRNA-based drugs, including many of which are encapsulated in lipid nanoparticles (LNPs) for improved drug delivery.
References
- Li, C., Wang, J., Wang, Y., et al. (2019). Recent progress in drug delivery. Acta Pharmaceutics Sinica B 9(6); 1145-1162. doi:10.1016/j.apsb.2019.08.003.
- Glassman, P. M., & Muzykantov, V. R. (2019). Pharmacokinetic and Pharmacodynamic Properties of Drug Delivery Systems. Journal of Pharmacology and Experimental Therapeutics 370(3); 570-580. doi:10.1124/jpet.119.257113.
- Karve, T., Dandekar, A., Agrahari, V., et al. (2024). Long-acting transdermal drug delivery formulations: Current developments and innovative pharmaceutical approaches. Advanced Drug Delivery Reviews 210. doi:1016/j.addr.2024.115326.
- Raijada, D., Wac, K., Greisen, E., et al. (2021). Integration of personalized drug delivery systems into digital health. Advanced Drug Delivery Reviews 176. doi:10.1016/j.addr.2021.113857.
- Qindeel, M., Irfan, M., Ullah, S., et al. (2024). Nanotechnology in glioblastoma therapy: Advances in drug delivery systems and diagnostic approaches. Journal of Drug Delivery Science and Technology 102(A). doi:10.1016/j.jddst.2024.106322.
- “The current and future value of mRNA vaccines and therapeutics” [Online]. Available from: https://curiaglobal.com/insights/current-and-future-value-of-mrna-vaccines-and-therapeutics/.
Further Reading
Navigating the complexities of controlled release drug formulations