Nanoparticles Brain Drug Delivery: Innovations in Targeted Therapy for Neurological Conditions

By Fouad Sabry

Nanoparticles for drug delivery to the brain-Introduces the significance of nanoparticles in targeting the brain for drug delivery and overcoming the bloodbrain barrier

Nanocapsule-Explores the structure and function of nanocapsules, their role in drug encapsulation, and their potential in brain therapies

Nanoparticle drug delivery-Discusses different nanoparticle systems and their applications in brain drug delivery to enhance therapeutic efficacy

Cytokine delivery systems-Examines the use of nanoparticles to deliver cytokines for modulating immune responses in neurological diseases

Cationic liposome-Focuses on the role of cationic liposomes in gene delivery and their effectiveness in treating brain disorders

Nanoparticle–biomolecule conjugate-Looks at the conjugation of nanoparticles with biomolecules for targeted and controlled drug delivery to the brain

Drug delivery to the brain-Provides an overview of various drug delivery methods and their mechanisms in penetrating the bloodbrain barrier

Nanogel-Investigates the application of nanogels in drug delivery, highlighting their advantages in controlled release and targeting brain tissues

Immunoliposome therapy-Describes the therapeutic use of immunoliposomes in targeting specific brain cells for precise drug delivery

Nanoneuroscience-Explores the intersection of nanotechnology and neuroscience, discussing how nanoparticles can revolutionize brain research and treatments

Intranasal drug delivery-Highlights the potential of intranasal drug delivery as a noninvasive method to administer drugs to the brain

Transcytosis-Delves into transcytosis, a process that enables nanoparticles to cross the bloodbrain barrier and deliver therapeutic agents effectively

Microbubble-Investigates the use of microbubbles in enhancing drug delivery to the brain, especially in combination with ultrasound technology

RNAi nanoparticles to target cancer-Explores the role of RNA interference (RNAi) in nanoparticles to target brain tumors and other cancerous cells

Blood–brain barrier-Provides an indepth understanding of the bloodbrain barrier, its challenges, and how nanoparticles can bypass it for drug delivery

Targeted drug delivery-Discusses strategies for targeted drug delivery, ensuring that therapeutic agents reach their intended brain targets effectively

Vectors in gene therapy-Explores the use of gene therapy vectors for treating neurological disorders and how nanoparticles can enhance gene delivery to the brain

Magnetic nanoparticles in drug delivery-Examines the use of magnetic nanoparticles to guide drugs to specific brain regions with precision

Focused ultrasound for intracranial drug delivery-Investigates the innovative use of focused ultrasound in conjunction with nanoparticles for targeted brain drug delivery

Blood–spinal cord barrier-Discusses the bloodspinal cord barrier and the strategies to deliver drugs across this barrier for treating spinal cord diseases

Lipidbased nanoparticle-Concludes with an examination of lipidbased nanoparticles, their role in drug delivery systems, and their application in brain treatments

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

Book preview

Chapter 1: Nanoparticles for drug delivery to the brain

Nanoparticles for drug delivery to the brain is a technique that involves the use of nanoparticles in order to transport drug molecules across the blood–brain barrier (BBB). In order to provide therapeutic therapy for neurological illnesses, these medications are able to pass through the blood-brain barrier and deliver pharmaceuticals to the brain. Patients suffering from Parkinson's disease, Alzheimer's disease, schizophrenia, depression, and brain tumors are included in this category of conditions. One of the reasons why it is so challenging to identify treatments for illnesses of the central nervous system (CNS) is that there is not currently a delivery technique that is truly effective in allowing medications to pass through the blood-brain barrier. There are a few instances of molecules that are unable to pass through the blood-brain barrier on their own. These include antibiotics, antineoplastic medicines, and a wide range of CNS-active medications, particularly neuropeptides. Nevertheless, studies have demonstrated that certain medications are now able to pass across the blood-brain barrier (BBB), and they even exhibit decreased toxicity and fewer harmful effects throughout the body. This is made possible by nanoparticle delivery methods. The notion of toxicity is an essential one in the field of pharmacology. This is due to the fact that high levels of toxicity in the body can have negative consequences for the patient by influencing other organs and disturbing their function. Moreover, the blood-brain barrier (BBB) is not the only physiological barrier that prevents drugs from reaching the brain. The manner in which medications are carried throughout the body and the manner in which they target particular regions for action are both influenced by other biological processes. Alterations in blood flow, edema and increased intracranial pressure, metabolic disturbances, and altered gene expression and protein synthesis are some of the pathophysiological mechanisms that might contribute to the development of this condition. Despite the fact that there are a great number of challenges that make the development of a reliable delivery system challenging, nanoparticles offer a potential route for the transportation of drugs to the central nervous system.

In 1995, a medication was successfully delivered across the blood-brain barrier for the very first time. An anti-nociceptive peptide called hexapeptide dalargin was utilized, which is unable to pass across the blood-brain barrier on its own. Intravenously administered nanoparticles that were coated with polysorbate 80 were used to encapsulate the substance. This was a significant technological advancement in the field of nanoparticle drug delivery, and it contributed to the advancement of research and development in the direction of clinical trials of nanoparticle delivery systems. The size of nanoparticles can range from 10 to 1000 nanometers, which is equivalent to 1 micrometer. Nanoparticles can be manufactured using natural or artificial polymers, lipids, dendrimers, and micelles. In order to reduce the risk of contamination in the central nervous system (CNS), the majority of the polymers that are utilized in nanoparticle drug delivery systems are natural, biocompatible, and biodegradable. Liposomes, prodrugs, and carrier-mediated transporters are some of the examples of the several ways that are now being utilized for the transportation of drugs to the brain. Peroral, intranasal, intravenous, and intracranial administration are just some of the many diverse delivery techniques that are available for the purpose of delivering these medications into the body. In the case of nanoparticles, the majority of research have demonstrated that intravenous distribution leads to an increasing advancement. Functionalizing, or activating, the nanoparticle carriers can be accomplished in a number of different ways, in addition to the delivery and transportation modalities they include. These methods include encapsulating a drug within the nanoparticle, attaching a drug to the surface of the nanoparticle, dissolving or absorbing a drug throughout the nanoparticle, and encapsulating a drug within the nanoparticle itself.

There is a type of nanoparticle that incorporates the utilization of liposomes as carriers for medicinal molecules. An example of a typical liposome is depicted in the diagram on the right. In order to differentiate the interior of the cell from the exterior of the cell, it possesses a phospholipid bilayer.

Sphingomyelin, phosphatidylcholine, and glycerophospholipids are examples of biocompatible and biodegradable lipids that are commonly used in the construction of liposomes. Liposomes are made up of vesicular bilayers, also known as lamellae. In addition, cholesterol, which is a type of lipid, is frequently included in the creation of lipid nanoparticle formulas. As a result of the fact that cholesterol's hydroxyl group is able to interact with the polar heads of the bilayer phospholipids, cholesterol has the capacity to both strengthen the stability of a liposome and inhibit the leakage of a bilayer. In addition to reducing toxicity and undesirable effects, liposomes have the ability to shield the drug from degradation, target specific locations for action, and target specific drugs. It is possible to generate lipid nanoparticles by the process of high pressure homogenization, which is currently utilized for the production of parenteral emulsions. By subdividing the particles until the desired consistency is achieved, this method has the potential to finally result in the formation of a homogeneous dispersion of microscopic droplets within a flexible substance. As a result of the fact that this manufacturing procedure has already been scaled up and is being utilized in the food sector, it is becoming increasingly interesting to researchers as well as the industry concerning drug delivery.

The surface of liposomes can also be functionalized by adding a variety of ligands, which can improve the delivery of drugs to specific areas of the brain.

A cationic liposome is yet another specific kind of lipid nanoparticle that has the potential to be utilized for the transport of drugs to the brain. These are molecules of lipids that have a positive charge inside of them. Bolaamphiphiles are an example of cationic liposomes. These liposomes have hydrophilic groups that surround a hydrophobic chain. The purpose of these bolaamphiphiles is to strengthening the boundary of the nano-vesicle that contains the medicine. The blood-brain barrier (BBB) can be traversed by bolaamphiphile nano-vesicles, which also enable the regulated delivery of the medicine to specific locations. Additionally, cationic liposomes and DNA solutions can be used to produce lipoplexes, which can then be used to produce transfection agents. A process known as adsorption-mediated endocytosis allows cationic liposomes to pass through the blood-brain barrier (BBB), which is then followed by internalization in the endosomes of endothelial cells. It is possible to influence the physical characteristics of endothelial cells by the process of transfection, which involves the utilization of lipoplexes. The way in which certain nanoparticle medication carriers traverse the blood-brain barrier might be improved as a result of these physical modifications.

The potential of metal nanoparticles as carriers for the delivery of drugs to the brain is quite intriguing. As a result of their biocompatibility, gold, silver, and platinum are frequently utilized in the process of nanoparticle drug delivery. Because of their enormous surface area to volume ratio, geometric and chemical tunability, and inherent antibacterial capabilities, these metallic nanoparticles are utilized in a variety of applications. The silver cations that are generated from the silver nanoparticles have the ability to bind to the negatively charged cellular membrane of bacteria. This phenomenon increases the membrane's permeability, which in turn allows foreign substances to enter the intracellular fluid.

The chemical synthesis of metal nanoparticles is accomplished by the use of reduction processes. For instance, drug-conjugated silver nanoparticles can be produced by reducing silver nitrate with sodium borohydride in the presence of an ionic drug molecule. This process is carried out in chemical reactions. Through the process of binding to the surface of the silver, the medication is able to stabilize the nanoparticles and prevent them from aggregating.

The BBB is frequently traversed by metallic nanoparticles through the process of transcytosis. over the introduction of peptide conjugates, which boost permeability to the central nervous system, it is possible to increase the distribution of nanoparticles over the blood-brain barrier (BBB). For example, recent research has demonstrated that conjugating a peptide that binds to transferrin receptors expressed in brain endothelial cells can boost the efficiency with which gold nanoparticles are delivered to the brain.

In addition, solid lipid nanoparticles, also known as SLNs, are lipid nanoparticles that have a solid interior, as demonstrated in the diagram on the right below. In order to produce SLNs, it is necessary to substitute a solid lipid for the liquid lipid oil that is utilized in the emulsion process. When it comes to solid lipid nanoparticles, the drug molecules are dissolved in the solid hydrophobic lipid core of the particle. This core is referred to as the drug payload, and it is surrounded by an aqueous solution. Triglycerides, fatty acids, and waxes are the primary components in the production of SLNs. Micro-emulsification and high-pressure homogenization are two methods that can be utilized in the production process. Therefore, increasing the permeability of the blood-brain barrier (BBB) can be accomplished by functionalizing the surface of solid lipid nanoparticles with polyethylene glycol (PEG). There are a variety of colloidal carriers, including liposomes, polymeric nanoparticles, and emulsions, that have decreased stability, shelf life, and encapsulation efficacy. Solid lipid nanoparticles are developed to address these disadvantages and have an excellent drug release and physical stability in addition to the capacity to deliver medications in a targeted manner.

Oil-in-water emulsions that are carried out on a nanoscale are yet another type of nanoparticle delivery mechanism. Through this method, typical biocompatible oils like triglycerides and fatty acids are combined with water and surface-coating surfactants. This procedure is used to create a surface coating. When it comes to entering the tight junctions of the blood-brain barrier, oils that are abundant in omega-3 fatty acids include specifically crucial elements that help.

Polymer-based nanoparticles are another type of nanoparticle. This type of nanoparticle is synthesized from a natural polymer, such as polylactic acid (PLA) or poly D,L-glycolide (PLG).

polycyanoacrylate (PCA) and polylactide-co-glycolide (PLGA) are two important materials. In comparison to lipid-based nanoparticles, polymeric nanoparticles have been discovered to have the potential to improve the stability of the medications or proteins that are being delivered. This is the reason why some studies have concluded that polymeric nanoparticles may produce superior results for drug delivery. The presence of advantageous controlled release mechanisms is another possibility for polymeric nanoparticles.

Nanoparticles that are manufactured from natural polymers and are biodegradable have the ability to target particular organs and tissues inside the body, to transport DNA for the purpose of gene therapy, and to deliver larger molecules such as proteins, peptides, and even genes. Before the drug molecules are encapsulated or connected to a polymer nanoparticle matrix, they are first dissolved. This is the initial step in the manufacturing process of these polymeric nanoparticles. Nanoparticles, nanocapsules (in which the drug is encapsulated and encircled by the polymer matrix), and nanospheres (in which the drug is spread throughout the polymeric matrix in a spherical form) are the three distinct forms that can be formed thereafter as a result of this