Intranasal drug delivery

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Intranasal drug delivery occurs when particles are inhaled into the nasal cavity and transported directly into the nervous system. Though pharmaceuticals can be injected into the nose, some concerns include injuries, infection, and safe disposal. Studies demonstrate improved patient compliance with inhalation. Treating brain diseases has been a challenge due to the blood brain barrier. Previous studies evaluated the efficacy of delivery therapeutics through intranasal route for brain diseases and mental health conditions. Intranasal administration is a potential route associated with high drug transfer from nose to brain and drug bioavailability. [1]

Contents

History of drug delivery

Drug delivery is a process of administering therapeutics to treat human diseases. The first drug delivery system often dates back to the 1950s, where Smith Kline & French Laboratories introduced the Spansule technology. [2] Between 1950s and 1980's, there were four drug release systems developed for oral and transdermal applications: dissolution, diffusion, osmosis, and ion-exchange controlled release. [3] Later in the 1980s, the Lupron Depot technology further advanced the field by offering zero-order and long-term release systems. Over the past few decades, the field has seen breathtaking advancements with improved drug formulations, release mechanisms, delivery materials, and administration routes. The intranasal route gained interest towards the end of the 20th century with treating cardiovascular and respiratory diseases. During the late 1980s, William Frey II studied the intranasal route for treating brain diseases. Ever since, it has become a potential route for nose-to-brain delivery.

Anatomy

Intranasal delivery pathway

Pathway of inhaled particles from nose to brain. Nose-to-Brain Drug Pathway.png
Pathway of inhaled particles from nose to brain.
The olfactory region contains the olfactory nerve and bulb. Olfactory nerve is a network of fibers which connect to the olfactory bulb. When particles reach the bulb, they have access to different regions of the brain. Olfactory region.png
The olfactory region contains the olfactory nerve and bulb. Olfactory nerve is a network of fibers which connect to the olfactory bulb. When particles reach the bulb, they have access to different regions of the brain.

The nasal cavity is highly vascularized which enables efficient transfer of molecules directly to the nervous system. When utilizing other routes of administration to target the brain, drug adsorption is low due to issues with systemic circulation effects and blood brain barrier. Drug delivery through nasal cavity increases drug bioavailability and lowers risk of systemic exposure. Nasal cavity is a slightly acidic environment with enzymes which can alter degradation of drug delivery systems. The delivery systems between neutral to acidic pH is ideal for high drug bioavailability following intranasal administration. The respiratory region of the cavity is the most vascularized with large surface area. These properties make it the primary site for drug transfer and absorption for systemic circulation. Targeting the olfactory region increases efficiency of nose-to-brain drug delivery. The olfactory region consists of the mucosal membrane consisting of the olfactory nerve connected to olfactory bulb. When particles are transmitted via the nerve fibers to olfactory bulb, they have direct access to the brain. Intranasal particles have to pass through the mucus layer, the first barrier, to then travel from nasal epithelium to brain. The mucosal membrane is negatively charged and contains hydrophobic domains. These properties affect drug diffusion. Overall, this delivery route is a potential route to treat brain diseases and mental health conditions.

Blood brain barrier

Depiction of all the different barriers in the brain. Focusing on (i), the blood brain barrier (BBB) is a highly selective membrane. It only allows passage of specific particles based on physiochemical properties. Protective barriers of the brain.jpg
Depiction of all the different barriers in the brain. Focusing on (i), the blood brain barrier (BBB) is a highly selective membrane. It only allows passage of specific particles based on physiochemical properties.

The blood brain barrier (BBB) is the semipermeable membrane lining the vascular network of the brain. More specifically, it is a barrier between blood and interstitial fluid of the brain. It is formed by the tight junctions between endothelial cells, astrocytes, and pericytes in the capillaries. The BBB has high electrical resistance. Some diseases can damage this barrier and cause leakage. It is crucial to maintain integrity. Researches suggest increased intake of vitamins and antioxidants as well as stress reduction can restore the blood brain barrier. This is the most highly selective barrier in the body that restricts passive diffusion of solutes, large and hydrophilic molecules, and immune factors. Two molecule properties that affect movement through BBB are surface activity and size. [4] The main purpose of this structure is to protect the brain from pathogens or toxic substances. The restrictive barrier maintains homeostasis and prevents any alterations to neuronal functions. Therefore, it is challenging to deliver pharmaceuticals directly to the brain.

Recent studies on nose-to-brain drug delivery

Alzheimer's

Neurodegenerative diseases occur from loss of neuronal structure and function. This progressive degeneration of neurons is irreversible. Alzheimer's is a neurodegenerative disease that begins with short-term memory loss progressing to loss of control over heartbeat and breathing. It has been over 100 years since Alois Alzheimer first presented the world disease to the world in 1906. There is evidence for the efficacy of intranasal delivery to treat Alzheimer's. Intranasal delivery of insulin showed greater memory improvement in patients with Alzheimer's than in healthy individuals. [5] Increased microglial activation inflammation are characteristics of Alzheimer's. Animal studies show intranasal administration of pro-resolving lipid mediators decreased both factors, slowing pathogenesis of this disease. [6] Delivering a novel peptide via intranasal route reduced amyloid beta plaques, a defining trait of Alzheimer's and enhanced cognitive functions. [7] Intranasal delivery of anti-Alzheimer's drug dispersed through hydrogel in rabbits demonstrated higher bioavailability compared to oral tablets. [8] MiR132 is an RNA molecule that regulates neuronal morphology and maintains survival. This molecule is downregulated with Alzheimer's. A study administered PEG-PLA nanoparticles loaded with this miRNA to mice through the nasal route. This novel therapy showed increased expression of miR132 and improved memory function. [9] To strengthen the effectiveness of intranasal delivery, there are studies to develop permeation enhancers to better improve drug transport across the blood brain barrier. [10]

Glioblastoma

Abnormal cell growth and formation of mass in the brain tissue or nearby regions may cause brain cancer. Constant headaches, seizures, and blurred vision are common symptoms. Glioblastoma (GBM) is the most fast-growing and deadliest brain tumor. Though the main cause of glioblastoma remains unknown, it originates when astrocytes mutate and multiply uncontrollably forming tumors in the frontal and temporal lobes of the brain. The challenge with current therapeutics is to initiate tumor cell apoptosis with no toxic effects to healthy brain tissue. Nanoparticles loaded with chemotherapeutics delivered through the intranasal route show promising results in treating glioblastoma. PLGA-based nanoparticles loaded with paclitaxel or doxorubicin conjugated with a RGD sequence targeted the glioblastoma microenvironment and reduced tumor volume through cell death. [11] [12] MicroRNA-21 (miR-21) inhibits pro-apoptotic genes increasing progression of glioblastoma. Self-assembling nanoparticles produced with anti-tumor peptides were administered intranasally and reduced miR-21 levels increasing tumor cell apoptosis. [13]

Epilepsy

Infection, head injury, or strokes can cause sudden bursts of neuronal activity leading to abnormal behaviors, muscle movement, and mood changes. This condition is known as seizure. Epilepsy is characterized by recurring seizures. Some possible causes of epilepsy include imbalance or disruption of neurotransmitters, strokes, or brain injury. Intranasal delivery of carbamazepine nanoparticles increase antiepileptic drug bioavailability. [14] Administering a self-assembling hydrogel with neuroactive drugs to treat Parkinson's disease appears to be biocompatible, low in toxicity, and have a good recovery capacity. Nasal delivery of this gel demonstrated increased drug concentration in the brain. [15] Oxytocin is a hormone which is observed to alleviate anxiety symptoms in people with autism. Intranasal administration indicated efficient transfer of pharmacologically active oxytocin from nasal cavity to brain. [16]

Parkinson's

Similar to Alzheimer's, Parkinson's is the most common neurodegenerative disease associated with balance and coordination issues, muscle stiffness, and tremors. During the early 1800s, James Parkinson medically defined this disease. A study observed improvement in locomotor abilities in rats with Parkinson's after intranasal delivery of conjugated mitochondrial systems. [17] Another study demonstrated delivery of neuroactive drugs in a hydrogel increased residence times in the nasal cavity and concentration in the brain. [18] Administering therapeutics combined with nanocarriers is shown to directly transfer drugs to the target cells and enhance accumulation. The observed effects include improved neuronal signaling and locomotion. [19] Furthermore, intranasal delivery of biodegradable nanoparticles surface-modified with lactoferrin increase accumulation in the brain and cellular uptake. [20]

Depression

Characterized by loss of neuroplasticity, depression is a common mood disorder causing persistent negative emotions and changes in lifestyle. Intranasal delivery of relaxin-3 mimetics demonstrated significant anti-depressant activity in behavior paradigms of rat models. [21] Delivering a thermoresponsive hydrogel loaded with berberine intranasally exhibited high bioavailability in hippocampus and anti-depressant activity. [22]

Anxiety

Anxiety can impair hippocampus function which increases risk of depression and dementia. Anxiolytic effects were observed in animal models post-intranasal delivery of a loaded polymeric nanoparticles. [23] Another study indicated intranasal delivery of neuropeptide Y lowered anxiety in rats. [24]

Anorexia nervosa

Anorexia nervosa (AN) is a common eating disorder characterized by low intake of food from fear of weight gain. Several complications are associated with this chronic disorder such as fatigue, insomnia, and low blood pressure. Intranasal administration of oxytocin in patients with AN significantly lowered food anticipation and eating concern. [25]

Substance use disorder

Uncontrolled and continuous use of a substance, drugs or alcohol, is known as substance use disorder. Substances can interfere with neuronal signaling and potentially disrupt the brain circuit. Addiction to these substances impairs thinking, behavior, and other biological functions. Intranasal delivery of insulin is associated with improvement in brain metabolic activities and alleviate impulsivity. [26] Opioid addiction is prevalent and associated with many substance abuse deaths. A study observed high biodistribution in the brain and reduction in opioid overdose in rats administered with naloxone-loaded lipid nanoparticles. [27]

Post-traumatic stress disorder

Witnessing a devastating or terrifying situation can lead to post-traumatic stress disorder (PTSD). This mental health condition triggers anxiety, depression, and extreme fear with memories. Intranasal administration of temperature-sensitive hydrogels loaded with PTSD medications showed enhanced brain targeting effects and tissue distribution. [28] Similarly, another study observed anti-PTSD effects with intranasal administration of loaded hydrogels. [29]

Schizophrenia

Schizophrenia is a chronic mental health condition caused by changes in brain chemistry and structure. Genetics and environment are hypothesized to play a key role in development of this disorder. Research suggests impaired gene expression or chemical imbalance may impact this condition. Anxiety can increase risk of schizophrenia and symptoms include hallucinations, disorganized speech, and abnormal behavior. Davunetide (NAP) is a segment of activity-dependent neuroprotective protein (ADNP). ADNP is reported be downregulated with schizophrenia. A study observed decreased hyperactivity in mice when treated with NAP via the intranasal route. [30]

Migraine

Migraine occurs with episodes of intense headache causing nausea and throbbing pain. Stress and hormonal changes can be a trigger migraine. A nasal spray containing sumatriptan demonstrated a significant reduction of migraine pain. Further clinical studies of intranasal administration of sumatriptan (ST) can help evaluate efficacy and safety of such delivery systems. [31]

Nanosystems for Intranasal Drug Delivery

Depiction of a lipid-based nanoparticle, liposome. The phospholipid bilayer exhibits amphipathic properties which allows encapsulation of hydrophilic and hydrophobic molecules. Liposome.jpg
Depiction of a lipid-based nanoparticle, liposome. The phospholipid bilayer exhibits amphipathic properties which allows encapsulation of hydrophilic and hydrophobic molecules.

Nanoparticles are drug delivery systems ranging from 1-1000 nm in diameter. Lipid-based and polymer-based nanocarriers are commonly used for nose-to-brain delivery as they exert high stability, solubility, and adherence. [32] Exosomes and dendrimers are other potential nanocarriers. Nanosystems can be synthesized either using physical or chemical methods. A few physical methods include evaporation-condensation reaction and laser ablation. Irradiation, microemulsion, and chemical reduction are common chemical techniques to develop nanoparticles. Sonication, electroporation, and incubation are common methods to load drugs into nanocarriers.

Coating these nanosystems with mucoadhesive agents, stimulus-sensitive materials, or antibodies can enhance biocompatibility, clearance rates, specificity, and bioavailability. Penetration and absorption enhancers can significantly increase the overall efficacy of the system. Imaging studies along with measurement of drug transfer efficiency and bioavailability can further support the role of these drug delivery systems.

Lipid-based nanoparticles

Lipid-based nanoparticles (LNP) can deliver molecules with low toxicity and controlled release. Liposomes, solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC), and nanoemulsions are examples.

Liposomes are made up of phospholipids forming spherical vesicles. This property enables liposomes to exhibit high biocompatibility and biodegradability. Studies report potential application of liposomes to treat brain diseases due to increased retention and absorption in nasal cavity, and high brain biodistribution. [33] A previous study developed a cationic liposome loaded with mRNA and green fluorescent protein (GFP). Intranasal delivery of this formulation in murine models demonstrated high brain biodistribution and expression of mRNA-GFP. [34]

Solid lipid nanoparticles (SLNs) are made up of solid lipids forming a matrix and stabilized by surfactants. They exhibit high physical stability and remain in solid state at different temperatures. Based on a study, intranasal delivery of SLNs loaded with rivastigmine tartrate (RT) exhibited no toxicity, stability, and improved bioavailability. [35] Sometimes burst release may occur due to rigidity and less flexibility in shape.

Nanostructured lipid carriers (NLC) are synthesized by a mixture of solid and aqueous lipids. NLC's are developed from SLNs, thus referred to as second generation LNPs. Intranasal administration of NLC loaded with curcumin (CRM) increased biodistribution and concentration in brain after emerging as a potential system for brain cancer. [36]

Small colloidal systems made of micelles containing oil, aqueous phases, and emulsifiers are called nanoemulsions. Intranasal delivery of gel nanoemulsion loaded with temozolomide is observed to exhibit sustained release and better permeation from nose to brain to treat glioblastoma. [37]

Polymer-based nanoparticles

Depiction of a type of polymer-based nanoparticle. Nanospheres contain a uniformly dispersed drug encapsulated in a polymeric core and matrix. Nanosphere.png
Depiction of a type of polymer-based nanoparticle. Nanospheres contain a uniformly dispersed drug encapsulated in a polymeric core and matrix.
Depiction of a polymer-based nanoparticle. Nanocapsules consist of drugs encapsulated in a polymeric membrane. Nanocapsule.png
Depiction of a polymer-based nanoparticle. Nanocapsules consist of drugs encapsulated in a polymeric membrane.

Polymer-based nanoparticles can be made from either natural or synthetic sources. Nanospheres and nanocapsules are polymeric nanoparticle systems. Natural polymers can be found in the environment or human body. On the other hand, synthetic polymers do not occur naturally and are artificially developed polymers with chemical modifications. Natural polymer-based nanoparticles can be made up of chitosan, hyaluronic acid, alginate, and gelatin. Natural polymers exhibit excellent biocompatibility and biodegradability, and low toxicity. Synthetic polymer-based nanoparticles can consist of poly (glycolic acid) (PGA), poly (lactic acid) (PLA), and poly(L-lactide-co-glycolide) (PLGA).

A study evaluated chitosan nanoparticles loaded with an anti-epileptic drug, phenytoin (PHT), to treat epilepsy. Observations suggested high stability, sustained release, and bioavailability when these particles where administered via the intranasal route. [38] Similarly, administering PLGA nanoparticles loaded lamotrigine (LTG), polymer-based nanoparticle, showed better permeation through BBB and higher bioavailability. [39]

Exosomes

Depiction of exosome formation. Following invagination of the plasma membrane, multivesicular bodies (MVBs) form and fuse with membrane to release exosomes. Exosome formation.png
Depiction of exosome formation. Following invagination of the plasma membrane, multivesicular bodies (MVBs) form and fuse with membrane to release exosomes.

Exosomes are vesicular structures containing genetic information. Recently, exosomes are being utilized as drug carriers. These systems are observed to be stable, specific, and safe. Moreover, delivery of exosomes shows less immunogenic affects. Further surface modifications and conjugation with liposomes enhances the therapeutic effects. Based on a previous study, intranasal delivery of exosomes loaded with a Stat3 inhibitor reduced brain inflammation and slowed brain tumor growth. [40]

Depiction of a dendrimer. A dendron represents a single unit of a dendrimer. Dendrimer and dendron.jpg
Depiction of a dendrimer. A dendron represents a single unit of a dendrimer.

Dendrimers

Dendrimers are polymeric macromolecules with a branched network similar to a tree structure. Generally, they are spherical and homogeneous. Surface charge and molecule chemistry can play crucial role with drug interaction and release. Poly(amidoamine) (PAMAM) dendrimers are the most commonly used system. A study investigated potential application of dendrimer-based formulation of haloperidol. Intranasal administration showed improved targeting, and solubility as well as high concentrations in the brain. [41] Drugs can be loaded in dendrimers through formulation and nanoconstruct. [42]

Importance of physiochemical properties

For drug delivery systems to bypass the blood brain barrier, modifications of physiochemical properties can enhance safety and efficacy. Size, surface charge, and lipophilicity play a major role in substance bypassing the blood brain barrier. Smaller, positively charged, or more lipophilic molecules enhance efficacy of nose-to-brain delivery. Decrease in delivery system size increases permeation. As the membrane is negatively charged, a particle with positive surface charge interacts electrostatically which enhances bioadhesion. Carriers with more lipophilicity exert better mucoadhesion and residence time. Drug system pH, solubility, and hydrogen bonding potential are other physiochemical properties which should be evaluated.

Related Research Articles

<span class="mw-page-title-main">Liposome</span> Composite structures made of phospholipids and may contain small amounts of other molecules

A liposome is a small artificial vesicle, spherical in shape, having at least one lipid bilayer. Due to their hydrophobicity and/or hydrophilicity, biocompatibility, particle size and many other properties, liposomes can be used as drug delivery vehicles for administration of pharmaceutical drugs and nutrients, such as lipid nanoparticles in mRNA vaccines, and DNA vaccines. Liposomes can be prepared by disrupting biological membranes.

<span class="mw-page-title-main">Dendrimer</span> Highly ordered, branched polymeric molecule

Dendrimers are highly ordered, branched polymeric molecules. Synonymous terms for dendrimer include arborols and cascade molecules. Typically, dendrimers are symmetric about the core, and often adopt a spherical three-dimensional morphology. The word dendron is also encountered frequently. A dendron usually contains a single chemically addressable group called the focal point or core. The difference between dendrons and dendrimers is illustrated in the top figure, but the terms are typically encountered interchangeably.

<span class="mw-page-title-main">Drug delivery</span> Methods for delivering drugs to target sites

Drug delivery refers to approaches, formulations, manufacturing techniques, storage systems, and technologies involved in transporting a pharmaceutical compound to its target site to achieve a desired therapeutic effect. Principles related to drug preparation, route of administration, site-specific targeting, metabolism, and toxicity are used to optimize efficacy and safety, and to improve patient convenience and compliance. Drug delivery is aimed at altering a drug's pharmacokinetics and specificity by formulating it with different excipients, drug carriers, and medical devices. There is additional emphasis on increasing the bioavailability and duration of action of a drug to improve therapeutic outcomes. Some research has also been focused on improving safety for the person administering the medication. For example, several types of microneedle patches have been developed for administering vaccines and other medications to reduce the risk of needlestick injury.

Targeted drug delivery, sometimes called smart drug delivery, is a method of delivering medication to a patient in a manner that increases the concentration of the medication in some parts of the body relative to others. This means of delivery is largely founded on nanomedicine, which plans to employ nanoparticle-mediated drug delivery in order to combat the downfalls of conventional drug delivery. These nanoparticles would be loaded with drugs and targeted to specific parts of the body where there is solely diseased tissue, thereby avoiding interaction with healthy tissue. The goal of a targeted drug delivery system is to prolong, localize, target and have a protected drug interaction with the diseased tissue. The conventional drug delivery system is the absorption of the drug across a biological membrane, whereas the targeted release system releases the drug in a dosage form. The advantages to the targeted release system is the reduction in the frequency of the dosages taken by the patient, having a more uniform effect of the drug, reduction of drug side-effects, and reduced fluctuation in circulating drug levels. The disadvantage of the system is high cost, which makes productivity more difficult, and the reduced ability to adjust the dosages.

<span class="mw-page-title-main">Nasal administration</span> Administration of drugs through the nose

Nasal administration, popularly known as snorting, is a route of administration in which drugs are insufflated through the nose. It can be a form of either topical administration or systemic administration, as the drugs thus locally delivered can go on to have either purely local or systemic effects. Nasal sprays are locally acting drugs such as decongestants for cold and allergy treatment, whose systemic effects are usually minimal. Examples of systemically active drugs available as nasal sprays are migraine drugs, rescue medications for overdose and seizure emergencies, nicotine replacement, and hormone treatments.

<span class="mw-page-title-main">Vectors in gene therapy</span>

Gene therapy utilizes the delivery of DNA into cells, which can be accomplished by several methods, summarized below. The two major classes of methods are those that use recombinant viruses and those that use naked DNA or DNA complexes.

<span class="mw-page-title-main">Sonodynamic therapy</span>

Sonodynamic therapy (SDT) is a noninvasive treatment, often used for tumor irradiation, that utilizes a sonosensitizer and the deep penetration of ultrasound to treat lesions of varying depths by reducing target cell number and preventing future tumor growth. Many existing cancer treatment strategies cause systemic toxicity or cannot penetrate tissue deep enough to reach the entire tumor; however, emerging ultrasound stimulated therapies could offer an alternative to these treatments with their increased efficiency, greater penetration depth, and reduced side effects. Sonodynamic therapy could be used to treat cancers and other diseases, such as atherosclerosis, and diminish the risk associated with other treatment strategies since it induces cytotoxic effects only when externally stimulated by ultrasound and only at the cancerous region, as opposed to the systemic administration of chemotherapy drugs.

Nanoparticles for drug delivery to the brain is a method for transporting drug molecules across the blood–brain barrier (BBB) using nanoparticles. These drugs cross the BBB and deliver pharmaceuticals to the brain for therapeutic treatment of neurological disorders. These disorders include Parkinson's disease, Alzheimer's disease, schizophrenia, depression, and brain tumors. Part of the difficulty in finding cures for these central nervous system (CNS) disorders is that there is yet no truly efficient delivery method for drugs to cross the BBB. Antibiotics, antineoplastic agents, and a variety of CNS-active drugs, especially neuropeptides, are a few examples of molecules that cannot pass the BBB alone. With the aid of nanoparticle delivery systems, however, studies have shown that some drugs can now cross the BBB, and even exhibit lower toxicity and decrease adverse effects throughout the body. Toxicity is an important concept for pharmacology because high toxicity levels in the body could be detrimental to the patient by affecting other organs and disrupting their function. Further, the BBB is not the only physiological barrier for drug delivery to the brain. Other biological factors influence how drugs are transported throughout the body and how they target specific locations for action. Some of these pathophysiological factors include blood flow alterations, edema and increased intracranial pressure, metabolic perturbations, and altered gene expression and protein synthesis. Though there exist many obstacles that make developing a robust delivery system difficult, nanoparticles provide a promising mechanism for drug transport to the CNS.

Nanoparticle drug delivery systems are engineered technologies that use nanoparticles for the targeted delivery and controlled release of therapeutic agents. The modern form of a drug delivery system should minimize side-effects and reduce both dosage and dosage frequency. Recently, nanoparticles have aroused attention due to their potential application for effective drug delivery.

Hamid Ghandehari is an Iranian-American drug delivery research scientist, and a professor in the Departments of Pharmaceutics and Pharmaceutical Chemistry and Biomedical Engineering at the University of Utah. His research is focused in recombinant polymers for drug and gene delivery, nanotoxicology of dendritic and inorganic constructs, water-soluble polymers for targeted delivery and poly(amidoamine) dendrimers for oral delivery.

A nasal vaccine is a vaccine administered through the nose that stimulates an immune response without an injection. It induces immunity through the inner surface of the nose, a surface that naturally comes in contact with many airborne microbes. Nasal vaccines are emerging as an alternative to injectable vaccines because they do not use needles and can be introduced through the mucosal route. Nasal vaccines can be delivered through nasal sprays to prevent respiratory infections, such as influenza.

Nanoneuroscience is an interdisciplinary field that integrates nanotechnology and neuroscience. One of its main goals is to gain a detailed understanding of how the nervous system operates and, thus, how neurons organize themselves in the brain. Consequently, creating drugs and devices that are able to cross the blood brain barrier (BBB) are essential to allow for detailed imaging and diagnoses. The blood brain barrier functions as a highly specialized semipermeable membrane surrounding the brain, preventing harmful molecules that may be dissolved in the circulation blood from entering the central nervous system.

Topical drug delivery (TDD) is a route of drug administration that allows the topical formulation to be delivered across the skin upon application, hence producing a localized effect to treat skin disorders like eczema. The formulation of topical drugs can be classified into corticosteroids, antibiotics, antiseptics, and anti-fungal. The mechanism of topical delivery includes the diffusion and metabolism of drugs in the skin. Historically, topical route was the first route of medication used to deliver drugs in humans in ancient Egyptian and Babylonian in 3000 BCE. In these ancient cities, topical medications like ointments and potions were used on the skin. The delivery of topical drugs needs to pass through multiple skin layers and undergo pharmacokinetics, hence factor like dermal diseases minimize the bioavailability of the topical drugs. The wide use of topical drugs leads to the advancement in topical drug delivery. These advancements are used to enhance the delivery of topical medications to the skin by using chemical and physical agents. For chemical agents, carriers like liposomes and nanotechnologies are used to enhance the absorption of topical drugs. On the other hand, physical agents, like micro-needles is other approach for enhancement ofabsorption. Besides using carriers, other factors such as pH, lipophilicity, and drug molecule size govern the effectiveness of topical formulation.

<span class="mw-page-title-main">Dextran drug delivery systems</span> Polymeric drug carrier

Dextran drug delivery systems involve the use of the natural glucose polymer dextran in applications as a prodrug, nanoparticle, microsphere, micelle, and hydrogel drug carrier in the field of targeted and controlled drug delivery. According to several in vitro and animal research studies, dextran carriers reduce off-site toxicity and improve local drug concentration at the target tissue site. This technology has significant implications as a potential strategy for delivering therapeutics to treat cancer, cardiovascular diseases, pulmonary diseases, bone diseases, liver diseases, colonic diseases, infections, and HIV.

<span class="mw-page-title-main">Focused ultrasound for intracranial drug delivery</span> Medical technique

Focused ultrasound for intracrainial drug delivery is a non-invasive technique that uses high-frequency sound waves to disrupt tight junctions in the blood–brain barrier (BBB), allowing for increased passage of therapeutics into the brain. The BBB normally blocks nearly 98% of drugs from accessing the central nervous system, so FUS has the potential to address a major challenge in intracranial drug delivery by providing targeted and reversible BBB disruption. Using FUS to enhance drug delivery to the brain could significantly improve patient outcomes for a variety of diseases including Alzheimer's disease, Parkinson's disease, and brain cancer.

<span class="mw-page-title-main">Reduction-sensitive nanoparticles</span> Drug delivery method

Reduction-sensitive nanoparticles (RSNP) consist of nanocarriers that are chemically responsive to reduction. Drug delivery systems using RSNP can be loaded with different drugs that are designed to be released within a concentrated reducing environment, such as the tumor-targeted microenvironment. Reduction-Sensitive Nanoparticles provide an efficient method of targeted drug delivery for the improved controlled release of medication within localized areas of the body.

pH-responsive tumor-targeted drug delivery is a specialized form of targeted drug delivery that utilizes nanoparticles to deliver therapeutic drugs directly to cancerous tumor tissue while minimizing its interaction with healthy tissue. Scientists have used drug delivery as a way to modify the pharmacokinetics and targeted action of a drug by combining it with various excipients, drug carriers, and medical devices. These drug delivery systems have been created to react to the pH environment of diseased or cancerous tissues, triggering structural and chemical changes within the drug delivery system. This form of targeted drug delivery is to localize drug delivery, prolongs the drug's effect, and protect the drug from being broken down or eliminated by the body before it reaches the tumor.

Ultrasound-triggered drug delivery using stimuli-responsive hydrogels refers to the process of using ultrasound energy for inducing drug release from hydrogels that are sensitive to acoustic stimuli. This method of approach is one of many stimuli-responsive drug delivery-based systems that has gained traction in recent years due to its demonstration of localization and specificity of disease treatment. Although recent developments in this field highlight its potential in treating certain diseases such as COVID-19, there remain many major challenges that need to be addressed and overcome before more related biomedical applications are clinically translated into standard of care.

<span class="mw-page-title-main">Intravesical drug delivery</span> Intravesical drug delivery, drug delivery to the bladder

Intravesical drug delivery is the delivery of medications directly into the bladder by urinary catheter. This method of drug delivery is used to directly target diseases of the bladder such as interstitial cystitis and bladder cancer, but currently faces obstacles such as low drug retention time due to washing out with urine and issues with the low permeability of the bladder wall itself. Due to the advantages of directly targeting the bladder, as well as the effectiveness of permeability enhancers, advances in intravesical drug carriers, and mucoadhesive, intravesical drug delivery is becoming more effective and of increased interest in the medical community.

Moein Moghimi is a British professor and researcher in the fields of nanomedicine, drug delivery and biomaterials. He is currently the professor of Pharmaceutics and Nanomedicine at the School of Pharmacy and the Translational and Clinical Research Institute at Newcastle University. He is also an adjoint professor at the Skaggs School of Pharmacy, University of Colorado Denver.

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