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. 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. Delivering a novel peptide via intranasal route reduced amyloid beta plaques, a defining trait of Alzheimer's and enhanced cognitive functions. Intranasal delivery of anti-Alzheimer's drug dispersed through hydrogel in rabbits demonstrated higher bioavailability compared to oral tablets. 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. To strengthen the effectiveness of intranasal delivery, there are studies to develop permeation enhancers to better improve drug transport across the blood brain barrier.
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. 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.
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. 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.
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.
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. Another study demonstrated delivery of neuroactive drugs in a hydrogel increased residence times in the nasal cavity and concentration in the brain. 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. Furthermore, intranasal delivery of biodegradable nanoparticles surface-modified with
lactoferrin increase accumulation in the brain and cellular uptake.
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. Delivering a
thermoresponsive hydrogel loaded with berberine intranasally exhibited high bioavailability in hippocampus and anti-depressant activity.
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. Another study indicated intranasal delivery of
neuropeptide Y lowered anxiety in rats.
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.
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.
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.
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. Similarly, another study observed anti-PTSD effects with intranasal administration of loaded hydrogels.
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.
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. Since its approval by the FDA in 2021, dihydroergotamine mesylate has been administered through nasal sprays to treat migraines. == Nanosystems for intranasal drug delivery ==