The field of Novel Drug Delivery Systems (NDDS) constantly seeks innovative routes and methods to deliver therapeutic agents in a manner that ensures improved efficacy, safety, and patient compliance.
One such route that has garnered significant attention over the years is the nasal route.
This mode of delivery bypasses the oral route, which is subject to first-pass metabolism and potential degradation in the harsh acidic environment of the stomach.
The nasal cavity, located between the base of the cranium and the roof of the mouth, provides a large surface area for absorption due to its rich vascularization.
The nasal mucosa, with its unique physicochemical properties, offers an environment conducive for drug absorption.
Furthermore, the presence of microvilli increases the surface area, making it even more attractive for drug delivery.
When drugs are administered through the nasal route, they can be targeted for local action (such as in the treatment of allergic rhinitis) or systemic action (bypassing the gastrointestinal tract and liver metabolism).
The nasal route has also been investigated for the delivery of vaccines and medications intended for brain delivery, given the nose-to-brain pathway.
Advantage Nasal Routes of Drug Delivery
1. Bypassing the First-pass Effect:
Nasal delivery circumvents hepatic first-pass metabolism, ensuring a higher bioavailability of drugs that undergo extensive first-pass degradation.
2. Rapid Onset of Action:
Due to the rich vasculature, drugs are quickly absorbed and show rapid onset.
3. Patient Compliance:
Nasal delivery is non-invasive, which could lead to better patient compliance compared to injectable routes.
4. Potential for CNS Delivery:
The nasal route may facilitate drug delivery to the brain via olfactory and trigeminal nerve pathways.
Disadvantages of Nasal Routes of Drug Delivery
1. Limited Volume:
Only limited volumes can be administered nasally.
2. Enzymatic Barrier
The nasal cavity contains enzymes that can degrade some drugs.
3. Potential Irritation:
Some formulations can irritate the nasal mucosa.
4. Mucociliary Clearance:
The presence of ciliary movement can clear the drug, reducing the residence time and absorption.
Mechanism of Nasal Absorption
1. Transcellular Transport:
This involves the passage of the drug through the epithelial cells. Lipophilic drugs, in general, prefer this pathway.
The drug diffuses across the cell membrane and traverses through the cell to reach the systemic circulation.
2. Paracellular Transport:
Hydrophilic drugs generally take this route, moving between the epithelial cells.
The tight junctions present between the cells regulate this pathway. If these junctions become more permeable, enhanced paracellular transport occurs.
3. Transcytosis:
Here, drugs are taken up by the cells in vesicles and are transported across the cell.
This process is particularly relevant for larger molecules like peptides and proteins.
4. Neuronal Transport:
Some drugs and molecules may get transported along the olfactory and trigeminal nerves to reach the central nervous system directly.
Factors Influencing Nasal Drug Absorption
1. Drug Properties:
Molecular Weight: Large molecules may find it challenging to permeate through the nasal mucosa.
Lipophilicity: A balance in lipophilicity is crucial. Highly lipophilic drugs may get entrapped in the lipidic environment of the membrane, whereas highly hydrophilic ones may not permeate efficiently.
2. Formulation Factors:
pH and Ionic Strength: The pH can influence the ionization status of the drug, affecting its absorption. Moreover, the pH should be compatible with the nasal environment to avoid irritation.
Viscosity: Increasing the viscosity might prolong the residence time, enhancing absorption. However, very viscous formulations might be challenging to administer.
Use of Absorption Enhancers: These are agents that can enhance the permeability of the nasal mucosa. For instance, surfactants, fatty acids, or chelating agents. Their use should be carefully considered due to potential irritation.
3. Physiological Factors:
Nasal Pathology: Conditions like rhinitis can alter the nasal environment, impacting drug absorption.
Mucociliary Clearance: The cilia present in the nasal mucosa move in a coordinated manner, pushing the mucus (and any entrapped drug particles) towards the throat, where it gets swallowed. This can affect the residence time of the drug.
Blood Flow: Regional blood flow can affect the drug uptake rate.
4. Device-Related Factors:
The design of the nasal delivery device can influence the deposition pattern and, consequently, the absorption. It's crucial to ensure that the device delivers the drug effectively to the desired region of the nasal cavity.