Targeted Drug Delivery: Advancements in Nanotechnology for Precision Medicine

By Fouad Sabry

In the rapidly evolving field of Nanomedicine, the importance of targeted drug delivery cannot be overstated. This book provides an indepth exploration of innovative drug delivery systems at the forefront of medical research, highlighting their potential in revolutionizing treatments for various diseases, particularly cancers and neurological disorders. Ideal for professionals, graduate and undergraduate students, and enthusiasts in the field, this comprehensive guide combines foundational concepts with cuttingedge developments

Targeted drug delivery-An introduction to the principles and mechanisms behind targeted drug delivery, offering insights into its applications in treating specific diseases

Reductionsensitive nanoparticles-Discusses nanoparticles designed to respond to specific redox conditions, a crucial aspect of controlled drug release for personalized therapy

Ligandtargeted liposome-Focuses on liposomes engineered with specific ligands to improve drug targeting efficiency, minimizing side effects

Microbubble-Explores microbubbles as drug delivery vehicles, emphasizing their role in enhancing therapeutic delivery through ultrasound

PHresponsive tumortargeted drug delivery-Examines pHsensitive systems that deliver drugs selectively to tumor sites, offering improved cancer treatment outcomes

Nanoparticle drug delivery-Reviews various nanoparticlebased systems used for targeted drug delivery, with emphasis on their versatility and efficacy

Sonodynamic therapy-Investigates sonodynamic therapy using nanomaterials to enhance drug activation through ultrasound, a promising approach in cancer therapy

Nanoparticles for drug delivery to the brain-Discusses the challenges and advancements in delivering drugs across the bloodbrain barrier using nanotechnology

Immunoliposome therapy-An overview of immunoliposomes, combining immunology and nanomedicine for highly targeted drug delivery in immunerelated disorders

Nanomedicine-Introduces the interdisciplinary field of nanomedicine, providing a foundational understanding of nanotechnology's role in medicine

Moein Moghimi-Honors the contributions of Moein Moghimi to the field, exploring his pioneering work in nanoparticle drug delivery systems

Arginylglycylaspartic acid-Focuses on the use of arginylglycylaspartic acid as a targeting ligand for efficient drug delivery systems

Magnetic nanoparticles in drug delivery-Highlights the use of magnetic nanoparticles for targeted drug delivery and their ability to be guided to specific sites via magnetic fields

Stimuliresponsive drug delivery systems-Discusses systems that release drugs in response to specific physiological triggers, improving precision in treatment

Chemotactic drugtargeting-Covers drug delivery strategies that exploit the body's natural chemical gradients for enhanced targeting

Nanocarrier-Examines different types of nanocarriers used in drug delivery, focusing on their design and role in improving drug solubility and bioavailability

Drug delivery-Provides a broad overview of drug delivery methods, including traditional and novel techniques for efficient and targeted treatments

Gated drug delivery systems-Introduces gated systems that control drug release based on external or internal signals, optimizing therapeutic outcomes

Protein nanoparticles-Focuses on the development and application of proteinbased nanoparticles for drug delivery, highlighting their biocompatibility and targeting abilities

Theranostics-Explores the emerging field of theranostics, where diagnostic and therapeutic functions are combined in one nanomedicine system for personalized treatment

Intranasal drug delivery-Investigates the potential of intranasal delivery systems for bypassing

• Language: English
• Publisher: One Billion Knowledgeable
• Release date: Mar 10, 2025

Book preview

Chapter 1: Targeted drug delivery

One approach of administering medication to a patient is known as targeted drug delivery, which is sometimes referred to as smart drug delivery. This technique involves administering the medication in a manner that raises the concentration of the medication in certain areas of the body in comparison to other areas. Nanomedicine, which intends to leverage nanoparticle-mediated drug delivery in order to fight the drawbacks of conventional drug delivery, is significantly responsible for contributing to the development of this method of dosage administration. These nanoparticles would be loaded with medications and directed to certain areas of the body where there is only diseased tissue. This would prevent the nanoparticles from interacting with healthy tissue. A targeted drug delivery system is designed to have the purpose of extending, localizing, targeting, and having a protected drug interaction with the tissue that is affected by the disease.  The standard method of drug delivery involves the medication being absorbed through a biological membrane. On the other hand, the targeted release method involves the drug being released in a dose form throughout the delivery process.  There are a number of benefits associated with the targeted release system, including a reduction in the frequency of dosages that the patient takes, a more uniform action of the drug, a reduction in the undesirable effects of the medicine, and a reduction in the fluctuations in the levels of the drug that are circulating in the body. Both the high expense of the system, which makes it more difficult to achieve productivity, and the decreased flexibility to change dosages are issues that are associated with the system.

It has proven possible to improve the effectiveness of regenerative treatments by developing targeted medication delivery systems. The system is based on a method that provides a certain quantity of a therapeutic agent to a diseased area within the body for an extended period of time. This method is responsible for delivering the therapeutic agent. Because of this, the needed plasma and tissue drug levels in the body are maintained, which helps to avoid any damage to the healthy tissue that could be caused by the drug from occurring.  Because the drug delivery system is highly integrated, it is necessary for professionals from a variety of fields, including chemists, biologists, and engineers, to collaborate in order to achieve optimal performance of this system.

Oral consumption and intravascular injection are two examples of classic methods of drug administration. These methods include the medication being absorbed by the body and then disseminated throughout the body through the systemic blood circulation. When it comes to the majority of therapeutic agents, only a small fraction of the medication is able to reach the organ that is being affected. If we take chemotherapy as an example, approximately 99 percent of the chemicals that are provided do not reach the site of the tumor. The goal of targeted drug delivery is to reduce the relative concentration of the medicine in the tissues that are not of interest while simultaneously increasing the concentration of the medication in the tissues that are of interest. As an illustration, a system is able to reach the desired site of action in larger concentrations if it circumvents the defense mechanisms of the host and inhibits non-specific distribution in the liver and spleen. Targeted delivery is thought to boost efficacy while simultaneously minimizing the number of adverse results.

When it comes to the implementation of a targeted release system, it is necessary to take into consideration the following design criteria for the system: the qualities of the medication, the adverse effects of the drug, the route that is followed for the delivery of the drug, the disease, and the targeted site.

The use of therapeutic agents whose adverse effects may be avoided through targeted drug delivery is the only way to achieve a controlled microenvironment, which is necessary for increasing the number of novel treatments that are being developed.  In order to regenerate heart tissue, advancements in the field of targeted medication delivery to cardiac tissue will be an essential component.

There are two types of targeted drug delivery: active targeted drug delivery, which includes some antibody drugs, and passive targeted drug delivery, which includes the improved permeability and retention effect (also known as the EPR-effect).

The capacity of nanoparticles to concentrate in regions of tissue that is solely affected by disease can be achieved by either passive or active targeting, or combination of these methods.

A therapeutic drug can be incorporated into a macromolecule or nanoparticle in order to accomplish passive targeting. This allows the therapeutic agent to reach the target organ without taking any active steps. The success of the medicine in passive targeting is directly proportional to the amount of time it spends in circulation. Wrapping the nanoparticle in a coating of some kind is the method that is used to accomplish this. Polyethylene glycol (PEG) is one of the compounds that can accomplish this, along with a number of other substances. Hydrophilicity is achieved by adding polyethylene glycol (PEG) to the surface of the nanoparticle. This makes it possible for water molecules to form hydrogen bonds with the oxygen molecules that are present on the PEG. The substance becomes antiphagocytic as a consequence of this connection, which results in a film of hydration surrounding the nanoparticle within the substance. It is because of the hydrophobic interactions that are inherent to the reticuloendothelial system (RES) that the particles acquire this ability. As a result, the drug-loaded nanoparticle is able to remain in circulation for a longer amount of time. Nanoparticles that are between 10 and 100 nanometers in size have been discovered to circulate systemically for extended periods of time. This is done in order to act in combination with the technique of passive targeting.

The benefits of passive targeting are amplified by active targeting of drug-loaded nanoparticles, which results in the nanoparticle being more specific to a target site. There are a number of different approaches that can be taken to fulfill active targeting. It is possible to actively target just sick tissue in the body by first determining the kind of a receptor on the cell that the medicine will be addressed to. This is one method. After that, researchers are able to make use of cell-specific ligands, which will make it possible for the nanoparticle to bind exclusively to the cell that possesses the complementary receptor. It was discovered that utilization of transferrin as the cell-specific ligand resulted in the successful execution of this active targeting technique. For the purpose of targeting tumor cells that have transferrin-receptor mediated endocytosis pathways on their membranes, the nanoparticle was conjugated with transferrin. As opposed to non-conjugated nanoparticles, it was discovered that this method of targeting was more effective in increasing absorption. An other ligand that is particular to cells is the RGD motif, which is capable of binding to the integrin αvβ3. The expression of this integrin is increased in tumor cells as well as activated endothelial cells. In vitro and in vivo studies have demonstrated that the conjugation of RGD to nanoparticles loaded with chemotherapeutic agents results in an increase in the absorption of the nanoparticles by cancer cells.

Utilizing magnetoliposomes, which are often used as a contrast agent in magnetic resonance imaging, is another method that can be utilized to accomplish active targeting. Therefore, magnetic placement could be of assistance in this process that involves grafting these liposomes with a medicine that is desired to be delivered to a certain region of the body.

Additionally, a nanoparticle may have the capability to be triggered by a trigger that is specific to the target region. For example, the utilization of materials that are pH responsive may be one way to accomplish this objective. Nanoparticles have the ability to take advantage of this ability by releasing the drug when it comes into contact with a specific pH. Another specific triggering mechanism is based on the redox potential. The majority of the body has a pH that is neutral and consistent. However, certain regions of the body are naturally more acidic than others. The redox potential in the area surrounding the tumor is altered as a result of hypoxia, which is one of the negative impacts that tumors can have. It is possible for the vesicles to be selective to various types of tumors by altering the redox potential that causes the payload release to occur.

When compared to a traditional drug, a drug-loaded nanoparticle has a significant benefit because it does not just use passive targeting but also active targeting. It is able to circulate throughout the body for a considerable amount of time until it is successfully attracted to its target by the utilization of cell-specific ligands, magnetic placement, or pH responsive components. This process can take a long time. It is because of these benefits that the adverse effects of conventional pharmaceuticals will be significantly decreased. This is because the nanoparticles loaded with the drug will only influence the tissue that is affected by the disease. On the other hand, a relatively new branch of study known as nanotoxicology is concerned about the possibility that nanoparticles themselves could be a danger to both human health and the environment on account of the side effects that they themselves produce. A drug targeting system that is based on peptides is another method that can be utilized to accomplish active targeting.

Polymeric micelles, liposomes, lipoprotein-based drug carriers, nano-particle drug carriers, dendrimers, and other types of drug delivery vehicles are just few of the many types of drug delivery vehicles. Not only should a drug delivery vehicle be non-toxic, biocompatible, non-immunogenic, and biodegradable, but it should also be able to escape being recognized by the immunological defense mechanisms of the host [3].

Within a target cell, medication distribution can be accomplished by the use of cell surface peptides as one method. In order to execute this strategy, the peptide binds to the surface receptors of the target cells in a manner that circumvents the immune defenses that would otherwise compromise a slower delivery. This method does not cause any harm to the host. Peptides, in particular, have demonstrated a significant amount of binding ability in a target cell. One example of this is the intercellular adhesion molecule-1. Therefore, as a result of this binding affinity, this approach has demonstrated some degree of efficacy in the treatment of autoimmune illnesses as well as many forms of cancer. The inexpensive cost of producing the peptides and the simplicity of their structure both contribute to the fact that peptide-mediated distribution is also a promising method.

In the present day, the liposome is the most often employed vehicle for the delivery of drugs in a targeted manner. Lipid-based, ligand-coated nanocarriers have the ability to store their payload in either the hydrophobic shell or the hydrophilic interior, depending on the nature of the drug or contrast agent that is being carried. Liposomes are non-toxic, non-hemolytic, and non-immunogenic even after repeated injections. They are also biocompatible and biodegradable, and they can be designed to avoid clearance mechanisms such as the reticuloendothelial system (RES), renal clearance, chemical or enzymatic inactivation, and so on.

Using liposomes in vivo presents just a few challenges, the most significant of which being their rapid uptake and clearance by the RES system, as well as their relatively low stability in vitro. PEG, which stands for polyethylene glycol, can be added to the surface of the liposomes in order to fight this issue. Increasing the mole percent of PEG on the surface of the liposomes by four to ten percent resulted in a considerable increase in circulation time in vivo, which went from two hundred to one thousand minutes.

Additionally, the passive targeting mechanism that is often associated with lipid-based nanocarriers is preserved through the process of PEGylation of the liposomal nanocarrier, which results in an extension of the half-life of the construct. When the construct is utilized as a delivery system, it is usual practice to take use of the capacity to induce instability in the construct. This enables the selective release of the encapsulated therapeutic substance in close proximity to the target tissue or cell in vivo. When it comes to anti-cancer treatments, this nanocarrier technology is frequently utilized because the acidity of the tumor mass, which is brought on by an excessive dependence on glycolysis, is what causes drug release.

Additional endogenous trigger pathways have been investigated by exploiting the inner and outer environments of tumors. These environments include reactive oxygen species, glutathione, enzymes, hypoxia, and adenosine-5'-triphosphate (ATP), all of which are typically found in and around tumors in high concentrations. Light, low frequency ultrasound (LFUS), electrical fields, and magnetic fields are some examples of the external triggers that are utilized. To be more specific, LFUS has been shown to be highly effective in the regulated administration of a variety of medications in mice, including cisplatin and calcein.

Polymeric micelles are yet another sort of drug delivery vehicle that is sometimes utilized. The preparation of these substances involves the utilization of specific amphiphilic co-polymers that are composed of both hydrophilic and hydrophobic monomer units. They have the capability of transporting medications that have a low solubility.  This approach does not provide much in the way of control over the size or the capacity to modify the function. The production of a bigger micelle that can be of varying sizes has been made possible through the development of techniques that make use of reactive polymers in conjunction with a hydrophobic ingredient.

Dendrimers are another type of delivery vehicle that is based on polymers.  The nanocarriers are small, spherical, and extremely dense. They have a core that branches out at regular intervals to generate the nanocarrier particles.

Biodegradable particles have the capacity to target sick tissue and deliver their payload in a controlled-release manner, making them an ideal candidate for therapeutic applications. It has been discovered that biodegradable particles that include ligands to P-selectin, endothelial selectin (E-selectin), and intercellular adhesion molecule-1 (ICAM-1) remain attached to inflammatory endothelium. Because of this, the utilization of biodegradable particles is also a viable option for heart tissue removal.

Active drug distribution in the lungs and the gastrointestinal system can be accomplished with the help of microrobots that are biocompatible with microalgae hybrid organisms. Tests conducted with mice demonstrated that the microrobots were effective. In all of the research investigations, Fluorescent dye or cell membrane–coated nanoparticle functionalized algae motors were further embedded inside a pH-sensitive capsule and simultaneously, antibiotic-loaded neutrophil membrane-coated polymeric nanoparticles [were attached] to natural microalgae