From the Guidelines
Intranasal administration is the most effective method for delivering Adipose-Derived Stem Cell (ADSC) exosomes to the brain, as it allows exosomes to bypass the blood-brain barrier and directly target the brain tissue. This approach is supported by the fact that intravascular delivery of mesenchymal stromal/stem cells, including those derived from adipose tissue, has been associated with risks of severe adverse events, such as thrombosis and embolization, as reported in a 2019 study published in Trends in Molecular Medicine 1. In contrast, intranasal delivery is a non-invasive and safer approach that enables exosomes to travel directly from the nasal cavity to the brain via the olfactory and trigeminal nerve pathways.
Key benefits of intranasal delivery include:
- Higher brain concentrations with lower doses
- Reduced systemic distribution
- Minimized potential side effects
- Ability to cross biological barriers due to their small size (30-150 nm)
- Protection of therapeutic cargo (proteins, miRNAs, growth factors) from degradation during transport, enhancing their neuroprotective, anti-inflammatory, and regenerative effects in the brain. For optimal delivery, a protocol typically involves administering 50-100 μg of purified ADSC exosomes in a volume of 20-50 μL, divided between both nostrils, with the patient in a head-back position for 5-10 minutes after administration to maximize absorption. The procedure should be performed under medical supervision and may be repeated every 1-2 weeks depending on the condition being treated.
From the Research
Effective Delivery Methods for ADSC Exosomes to the Brain
The most effective method for delivering Adipose-Derived Stem Cells (ADSC) exosomes to the brain is a subject of ongoing research. Based on existing studies, the following methods have been explored:
- Intranasal delivery: This method has shown promise in bypassing the blood-brain barrier and delivering therapeutic agents directly to the brain 2, 3, 4, 5, 6.
- Intravenous delivery: While this method is commonly used for systemic administration, its effectiveness in delivering ADSC exosomes to the brain is limited due to the blood-brain barrier.
- Nebulization: There is limited research on the use of nebulization for delivering ADSC exosomes to the brain.
Intranasal Delivery Mechanism
The intranasal delivery mechanism involves the transport of drugs or therapeutic agents from the nasal cavity to the brain along the olfactory and trigeminal nerves 6. This mechanism can be divided into two pathways:
- Intracellular pathway: This pathway involves the endocytosis of therapeutic agents by olfactory sensory cells, followed by axonal transport to the olfactory bulb and subsequent distribution to other brain regions.
- Extracellular mechanism: This mechanism involves the transport of therapeutic agents directly into the cerebral spinal fluid through the paracellular space across the nasal epithelium and the perineural space to the subarachnoid space of the brain.
Advantages of Intranasal Delivery
Intranasal delivery offers several advantages, including:
- Non-invasive method: Intranasal delivery is a non-invasive method that bypasses the blood-brain barrier, reducing the risk of systemic side effects 2, 3, 4.
- Direct delivery: Intranasal delivery allows for direct delivery of therapeutic agents to the brain, reducing the time and amount of drug required to achieve therapeutic effects 2, 6.
- Wide range of therapeutics: Intranasal delivery can be used to deliver a wide range of therapeutics, including small molecules, macromolecules, and exosomes 3, 5.