Targeted drug delivery
Targeted drug delivery, sometimes called smart drug delivery,
Targeted drug delivery systems have been developed to optimize regenerative techniques. The system is based on a method that delivers a certain amount of a therapeutic agent for a prolonged period of time to a targeted diseased area within the body. This helps maintain the required plasma and tissue drug levels in the body, thereby preventing any damage to the healthy tissue via the drug. The drug delivery system is highly integrated and requires various disciplines, such as chemists, biologists, and engineers, to join forces to optimize this system.[2]
Background
In traditional
When implementing a targeted release system, the following design criteria for the system must be taken into account: the drug properties, side-effects of the drugs, the route taken for the delivery of the drug, the targeted site, and the disease.
Increasing developments to novel treatments requires a controlled microenvironment that is accomplished only through the implementation of therapeutic agents whose side-effects can be avoided with targeted drug delivery. Advances in the field of targeted drug delivery to cardiac tissue will be an integral component to regenerate cardiac tissue.[5]
There are two kinds of targeted drug delivery: active targeted drug delivery, such as some antibody medications, and passive targeted drug delivery, such as the enhanced permeability and retention effect (EPR-effect).
Targeting methods
This ability for nanoparticles to concentrate in areas of solely diseased tissue is accomplished through either one or both means of targeting: passive or active.
Passive targeting
Passive targeting is achieved by incorporating the therapeutic agent into a macromolecule or nanoparticle that passively reaches the target organ. In passive targeting, the drug's success is directly related to circulation time.[6] This is achieved by cloaking the nanoparticle with some sort of coating. Several substances can achieve this, with one of them being polyethylene glycol (PEG). By adding PEG to the surface of the nanoparticle, it is rendered hydrophilic, thus allowing water molecules to bind to the oxygen molecules on PEG via hydrogen bonding. The result of this bond is a film of hydration around the nanoparticle which makes the substance antiphagocytic. The particles obtain this property due to the hydrophobic interactions that are natural to the reticuloendothelial system (RES), thus the drug-loaded nanoparticle is able to stay in circulation for a longer period of time.[7] To work in conjunction with this mechanism of passive targeting, nanoparticles that are between 10 and 100 nanometers in size have been found to circulate systemically for longer periods of time.[8]
Active targeting
Active targeting of drug-loaded nanoparticles enhances the effects of passive targeting to make the nanoparticle more specific to a target site. There are several ways that active targeting can be accomplished. One way to actively target solely diseased tissue in the body is to know the nature of a receptor on the cell for which the drug will be targeted to.[9] Researchers can then utilize cell-specific ligands that will allow the nanoparticle to bind specifically to the cell that has the complementary receptor. This form of active targeting was found to be successful when utilizing transferrin as the cell-specific ligand.[9] The transferrin was conjugated to the nanoparticle to target tumor cells that possess transferrin-receptor mediated endocytosis mechanisms on their membrane. This means of targeting was found to increase uptake, as opposed to non-conjugated nanoparticles. Another cell-specific ligand is the RGD motif which binds to the integrin αvβ3.[10] This integrin is upregulated in tumor and activated endothelial cells.[11] Conjugation of RGD to chemotherapeutic-loaded nanoparticles has been shown to increase cancer cell uptake in vitro and therapeutic efficacy in vivo.[10]
Active targeting can also be achieved by utilizing magnetoliposomes, which usually serves as a contrast agent in magnetic resonance imaging.[9] Thus, by grafting these liposomes with a desired drug to deliver to a region of the body, magnetic positioning could aid with this process.
Furthermore, a nanoparticle could possess the capability to be activated by a trigger that is specific to the target site, such as utilizing materials that are pH responsive.[9] Most of the body has a consistent, neutral pH. However, some areas of the body are naturally more acidic than others, and, thus, nanoparticles can take advantage of this ability by releasing the drug when it encounters a specific pH.[9] Another specific triggering mechanism is based on the redox potential. One of the side effects of tumors is hypoxia, which alters the redox potential in the vicinity of the tumor. By modifying the redox potential that triggers the payload release the vesicles can be selective to different types of tumors.[12]
By utilizing both passive and active targeting, a drug-loaded nanoparticle has a heightened advantage over a conventional drug. It is able to circulate throughout the body for an extended period of time until it is successfully attracted to its target through the use of cell-specific ligands, magnetic positioning, or pH responsive materials. Because of these advantages, side effects from conventional drugs will be largely reduced as a result of the drug-loaded nanoparticles affecting only diseased tissue.[13] However, an emerging field known as nanotoxicology has concerns that the nanoparticles themselves could pose a threat to both the environment and human health with side effects of their own.[14] Active targeting can also be achieved through peptide based drug targeting system.[15]
Delivery vehicles
There are different types of drug delivery vehicles, such as polymeric micelles, liposomes, lipoprotein-based drug carriers, nano-particle drug carriers, dendrimers, etc. An ideal drug delivery vehicle must be non-toxic, biocompatible, non-immunogenic, biodegradable,[5] and must avoid recognition by the host's defense mechanisms[3].
Peptides
Cell Surface Peptides provide one way to introduce drug delivery into a target cell.[16] This method is accomplished by the peptide binding to a target cells surface receptors, in a way that bypasses immune defenses that would otherwise compromise a slower delivery, without causing harm to the host. In particular, peptides, such as intercellular adhesion molecule-1, have shown a great deal of binding ability in a target cell. This method has shown a degree of efficacy in treating both autoimmune diseases as well as forms of cancer as a result of this binding affinity.[17] Peptide mediated delivery is also of promise due to the low cost of creating the peptides as well as the simplicity of their structure.
Liposomes
The most common vehicle currently used for targeted drug delivery is the
The only problem to using liposomes in vivo is their immediate uptake and clearance by the RES system and their relatively low stability in vitro. To combat this, polyethylene glycol (PEG) can be added to the surface of the liposomes. Increasing the mole percent of PEG on the surface of the liposomes by 4-10% significantly increased circulation time in vivo from 200 to 1000 minutes.[5]
PEGylation of the liposomal nanocarrier elongates the half-life of the construct while maintaining the passive targeting mechanism that is commonly conferred to lipid-based nanocarriers.[22] When used as a delivery system, the ability to induce instability in the construct is commonly exploited allowing the selective release of the encapsulated therapeutic agent in close proximity to the target tissue/cell in vivo. This nanocarrier system is commonly used in anti-cancer treatments as the acidity of the tumour mass caused by an over-reliance on glycolysis triggers drug release.[22][23][24]
Additional endogenous trigger pathways have been explored through the exploitation of inner and outer tumor environments, such as reactive oxygen species, glutathione, enzymes, hypoxia, and adenosine-5’- triphosphate (ATP), all of which are generally highly present in and around tumors.[25] External triggers are also used, such as light, low frequency ultrasound (LFUS), electrical fields, and magnetic fields.[26] In specific, LFUS has demonstrated high efficacy in the controlled trigger of various drugs in mice, such as cisplatin and calcein.[27][28]
Micelles and dendrimers
Another type of drug delivery vehicle used is polymeric
Dendrimers are also polymer-based delivery vehicles. They have a core that branches out in regular intervals to form a small, spherical, and very dense nanocarrier.[30]
Biodegradable particles
Biodegradable particles have the ability to target diseased tissue as well as deliver their payload as a
Microalgae-based delivery
This section is missing information about other prototypes and the approach more generally and needs reviews and further work.(November 2022) |
There are biocompatible
Artificial DNA nanostructures
The success of
Applications
Targeted drug delivery can be used to treat many diseases, such as the
The American Heart Association rates cardiovascular disease as the number one cause of death in the United States. Each year 1.5 million myocardial infarctions (MI), also known as heart attacks, occur in the United States, with 500,000 leading to deaths. The costs related to heart attacks exceed $60 billion per year. Therefore, there is a need to come up with an optimum recovery system. The key to solving this problem lies in the effective use of pharmaceutical drugs that can be targeted directly to the diseased tissue. This technique can help develop many more regenerative techniques to cure various diseases. The development of a number of regenerative strategies in recent years for curing heart disease represents a paradigm shift away from conventional approaches that aim to manage heart disease.[5]
See also
- Targeted therapy
- Nanomedicine
- Nanobiotechnology § Nanomedicine
- Antibody-drug conjugate
- Retrometabolic drug design
- Magnetic drug delivery
- PH-responsive tumor-targeted drug delivery
References
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- ^ Trafton, A. Tumors Targeted Using Tiny Gold Particles. MIT Tech Talk. 2009, 53, 4–4.
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- ^ S2CID 71338475.
- ^ Sagnella, S.; Drummond, C. Drug Delivery: A Nanomedicine Approach. Australian Biochemist. [Online] 2012, 43, 5–8, 20. The Australian Society for Biochemistry and Molecular Biology.
- ^ Vlerken, L. E. V.; Vyas, T. K.; Amiji, M. M. Poly(Ethylene Glycol)-Modified Nanocarriers for Tumor-Targeted and Intracellular Delivery. Pharm. Res. 2007, 24, 1405–1414.
- ^ a b Gullotti, E.; Yeo, Y. Extracellularly Activated Nanocarriers: A New Paradigm of Tumor Targeted Drug Delivery. Mol. Pharm., [Online] 2009, 6, 1041-1051. ACS Publications.
- ^ a b c d e Galvin, P.; Thompson, D.; Ryan, K. B.; Mccarthy, A.; Moore, A. C.; Burke, C. S.; Dyson, M.; Maccraith, B. D.; Gun’Ko, Y. K.; Byrne, M. T.; Volkov, Y.; Keely, C.; Keehan, E.; Howe, M.; Duffy, C.; Macloughlin, R. Nanoparticle-Based Drug Delivery: Case Studies for Cancer and Cardiovascular Applications. Cell. Mol. Life Sci. [Online] 2011, 69, 389–404.
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- ^ Mitra, A. K.; Kwatra, D.; Vadlapudi, A. D. Drug Delivery; Jones & Bartlett Learning: Burlington, Massachusetts, 2015.
- ^ Jong, W. H. D.; Borm, P. J. A. Drug Delivery and Nanoparticles: Applications and Hazards. Int. J. Nanomedicine. [Online] 2008, 3, 133–149. The National Center for Biotechnology Information.
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- ^ Torchilin, VP “Multifunctional Nanocarriers.” Adv Drug Deliv Rev 2006 Dec; 58 (14): 1532-55 doi: 10.1016/j.addr.2006.09.009
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- ^ Macosko, Cristopher W. "Polymer Nanoparticles Improve Delivery of Compounds” University of Minnesota Office for Technology Commercialization."Nanodelivery". Archived from the original on 2012-03-24.
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{{cite journal}}
: CS1 maint: numeric names: authors list (link - ^ "Algae micromotors join the ranks for targeted drug delivery". Chemical & Engineering News. Retrieved 19 October 2022.
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- ^ Kahan, M; Gil, B; Adar, R; Shapiro, E (2008). "Towards Molecular Computers that Operate in a Biological Environment". .
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- ^ Medscape from WebMD [Internet]. New York: WebMD LLC; 1994-2015. Liposomes as Drug Delivery Systems for the Treatment of TB; 2011 [cited 2015 May 8] Available from: http://www.medscape.com/viewarticle/752329_3
- ^ Hirschler, Ben (December 16, 2014). "3D Printing Points Way to Smarter Cancer Treatment". Reuters. London.
Further reading
- Schroeder, Avi; Honen, Reuma; Turjeman, Keren; Gabizon, Alberto; Kost, Joseph; Barenholz, Yechezkel (2009). "Ultrasound triggered release of cisplatin from liposomes in murine tumors". Journal of Controlled Release. 137 (1): 63–8. PMID 19303426.
- Scott, Robert C.; Wang, Bin; Nallamothu, Ramakrishna; Pattillo, Christopher B.; Perez-Liz, Georgina; Issekutz, Andrew; Valle, Luis Del; Wood, George C.; Kiani, Mohammad F. (2007). "Targeted delivery of antibody conjugated liposomal drug carriers to rat myocardial infarction". Biotechnology and Bioengineering. 96 (4): 795–802. S2CID 30039741.
- Scott, Robert C; Crabbe, Deborah; Krynska, Barbara; Ansari, Ramin; Kiani, Mohammad F (2008). "Aiming for the heart: targeted delivery of drugs to diseased cardiac tissue". Expert Opinion on Drug Delivery. 5 (4): 459–70. S2CID 71338475.
- Wang, Bin; Rosano, Jenna M; Cheheltani, Rabe'e; Achary, Mohan P; Kiani, Mohammad F (2010). "Towards a targeted multi-drug delivery approach to improve therapeutic efficacy in breast cancer". Expert Opinion on Drug Delivery. 7 (10): 1159–73. S2CID 19679654.
- Wang, Bin; Scott, Robert C.; Pattillo, Christopher B.; Prabhakarpandian, Balabhaskar; Sundaram, Shankar; Kiani, Mohammad F. (2008). "Modeling Oxygenation and Selective Delivery of Drug Carriers Post-Myocardial Infarction". In Kang, Kyung A.; Harrison, David K.; Bruley, Duane F. (eds.). Oxygen Transport to Tissue XXIX. Advances in Experimental Medicine and Biology. Vol. 614. Springer. pp. 333–43. PMID 18290344.
- YashRoy R.C. (1999) Targeted drug delivery.Proceedings ICAR Short Course on "Recent approaches on clinical pharmacokinetics and therapeutic monitoring of drugs in farm animals", Oct 25 to Nov 3, 1999, Div of Pharmacology and Toxicology, IVRI, Izatnagar (India), pp. 129–136. https://www.researchgate.net/publication/233426779_Targeted_drug_delivery?ev=prf_pub