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Government College of Pharmacy, Vidyanagar, Karad.
Intranasal nanomedicine has emerged as a promising non-invasive strategy for direct nose-to-brain drug delivery, offering an effective alternative to conventional routes for treating neurological and psychiatric disorders. The major challenge in central nervous system (CNS) therapy is the presence of the blood–brain barrier (BBB), which restricts the entry of most therapeutic agents into the brain. Intranasal administration bypasses this barrier through olfactory and trigeminal neural pathways, enabling rapid and targeted drug delivery with reduced systemic exposure and improved patient compliance. Nanocarrier-based systems such as nanoparticles, nano-emulsions, liposomes, and lipid-based carriers play a crucial role in enhancing drug stability, permeability, and bioavailability while protecting drugs from enzymatic degradation. These systems also improve nasal residence time and allow controlled and sustained drug release. Intranasal nanomedicine has shown significant potential in the management of disorders such as Alzheimer’s disease, Parkinson’s disease, epilepsy, brain tumors, and various psychiatric conditions. Despite its advantages, several challenges remain, including mucociliary clearance, limited dosing volume, enzymatic barriers, variability in drug absorption, and difficulties in targeting the olfactory region. Additionally, issues related to formulation optimization, safety, and large-scale clinical translation persist. Recent advances in nanotechnology, formulation strategies, and delivery devices are addressing these limitations and improving therapeutic outcomes. With continued research and clinical validation, intranasal nanomedicine holds significant potential to become an effective and innovative platform for brain-targeted drug delivery in the future
Neurological and psychiatric disorders, including neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease, as well as conditions like depression and schizophrenia, represent a growing global health burden. The increasing prevalence of these disorders, particularly with aging populations, has significantly contributed to rising healthcare costs and societal impact . Despite advances in pharmacotherapy, effective treatment remains challenging due to limited drug access to the central nervous system (CNS) and suboptimal therapeutic outcomes. One of the major obstacles in brain drug delivery is the presence of the blood–brain barrier (BBB), a highly selective physiological barrier that restricts the entry of most therapeutic agents into the brain. The BBB is composed of tightly joined endothelial cells and active efflux transport systems, allowing only small, lipophilic molecules or those with specific transport mechanisms to pass through [1]. As a result, approximately 98% of small molecules and nearly all large biomolecules fail to reach the brain in therapeutically effective concentrations. Conventional drug delivery routes such as oral and parenteral administration are further limited by first-pass metabolism, systemic clearance, and peripheral side effects, leading to reduced bioavailability and therapeutic efficacy [2]. To overcome these limitations, intranasal drug delivery has emerged as a promising non-invasive approach for direct nose-to-brain transport. This strategy exploits the unique anatomical and physiological connection between the nasal cavity and the CNS, enabling drugs to bypass the BBB. Drug molecules administered intranasally can reach the brain via the olfactory and trigeminal nerve pathways, facilitating rapid and targeted delivery [1]. Additionally, this route minimizes systemic exposure, avoids hepatic first-pass metabolism, and offers improved patient compliance [3]. However, challenges such as mucociliary clearance, enzymatic degradation, and limited residence time in the nasal cavity can affect drug absorption and delivery efficiency [2]. In recent years, nanomedicine-based approaches have been extensively explored to enhance the efficiency of intranasal drug delivery. Nanocarriers such as nanoemulsion, nanoparticles, and liposomes can improve drug stability, permeability, and targeting while enabling controlled and sustained release. For instance, nanoemulsion systems have demonstrated enhanced permeability and brain targeting efficiency due to their small droplet size and increased surface area, facilitating improved transport across the nasal mucosa [4]. Furthermore, the incorporation of mucoadhesive agents can prolong nasal residence time and enhance drug absorption. Despite significant progress, intranasal nanomedicine for nose-to-brain delivery is still an emerging field with several challenges, including formulation optimization, safety concerns, and limited clinical translation. Most studies remain at the preclinical stage, and only a few formulations have reached clinical approval, highlighting the need for further research and development [2]. Therefore, this review aims to comprehensively discuss emerging intranasal nanomedicine strategies for direct nose-to-brain delivery, focusing on their mechanisms, types of nanocarriers, therapeutic applications in neurological and psychiatric disorders, and current challenges along with future perspectives.
2.1 Structure of the Nasal Cavity
The nasal cavity is divided into two symmetrical halves by the nasal septum and serves as an important interface for respiration and olfaction. It provides a large surface area for drug absorption and is lined with a highly vascularized mucosal layer [1].
Anatomically, the nasal cavity is divided into three regions:
The anterior portion of the nasal cavity, lined with stratified squamous epithelium and nasal hairs, primarily functions in filtration. Due to its small surface area, it plays a minimal role in drug absorption [1].
This is the largest region and consists of pseudostratified ciliated columnar epithelium with goblet cells. It is highly vascularized and serves as the main site for systemic drug absorption [5].
Located in the upper part of the nasal cavity, this region contains olfactory neurons that connect directly to the brain via the olfactory bulb, making it crucial for direct nose-to-brain drug delivery [5].
The nasal mucosa consists of epithelial cells, goblet cells, basal cells, and ciliated cells embedded in a mucus layer. This mucus layer acts as a protective barrier by trapping particles and pathogens, but it can also hinder drug diffusion [6]. Ciliated cells are responsible for mucociliary clearance, a mechanism that transports mucus toward the nasopharynx, resulting in rapid removal of administered drugs and reduced residence time [7]. Additionally, enzymes present in the nasal mucosa may degrade drugs before absorption, further limiting delivery efficiency [6].
The nasal cavity is uniquely connected to the central nervous system through the olfactory and trigeminal nerves, enabling direct nose-to-brain drug delivery.
Olfactory neurons extend from the nasal epithelium to the olfactory bulb through the cribriform plate, providing a direct route for drug transport to the brain and bypassing the blood–brain barrier ..
The trigeminal nerve innervates the respiratory region and provides an alternative pathway for drug transport to deeper brain regions such as the brainstem .
These pathways allow both intracellular and extracellular transport mechanisms, facilitating rapid drug delivery to the brain [5].
Several physiological factors influence intranasal drug delivery:
These challenges necessitate the use of advanced formulation strategies such as nanocarriers and mucoadhesive systems to enhance drug retention and brain targeting.
3.1 Overview of Nose-to-Brain Transport
Intranasal drug delivery enables direct transport of therapeutic agents from the nasal cavity to the brain, bypassing the blood–brain barrier (BBB). This unique delivery route occurs through multiple pathways, including olfactory, trigeminal, and systemic transport mechanisms. These pathways allow rapid drug absorption and targeted delivery to the central nervous system (CNS) (2,5).
The olfactory pathway is the most important route for direct nose-to-brain drug delivery. The olfactory epithelium contains olfactory receptor neurons that extend from the nasal cavity to the olfactory bulb through the cribriform plate.
Drugs can be transported via:
Drugs are internalized into olfactory neurons and transported along axons to the brain. This process is relatively slow and may take hours to days.
Drugs move along perineural channels or intercellular spaces, allowing rapid transport to the brain within minutes.
Studies have shown that nanoparticles can reach the olfactory bulb within minutes after intranasal administration, indicating the efficiency of this pathway [2,5]
The trigeminal nerve pathway provides an additional route for drug delivery to the brain. The trigeminal nerve innervates both the respiratory and olfactory regions of the nasal cavity and connects to deeper brain structures such as the brainstem.
Drugs transported through this pathway can reach:
Transport occurs via both intracellular and extracellular mechanisms, similar to the olfactory pathway. This pathway is particularly important for delivering drugs to posterior brainregions (2).
In addition to direct transport, some drugs are absorbed into the systemic circulation through the highly vascularized nasal mucosa and subsequently reach the brain by crossing the BBB.
However, this route has limitations:
Only small, lipophilic molecules can efficiently cross the BBB via this pathway (8).
Drug transport across the nasal epithelium occurs via different cellular mechanisms:
Drug molecules pass through epithelial cells via passive diffusion or carrier-mediated transport.
Movement of drugs through tight junctions between cells (limited for large molecules).
Particularly important for nanoparticles, which can be internalized by epithelial cells and transported across the membrane (9).
Nanoparticles have been shown to cross biological barriers via transcytosis, enhancing brain delivery efficiency (8)
Several factors determine the efficiency of nose-to-brain delivery:
Formulation strategies such as mucoadhesive nanoparticles and surface-modified carriers can significantly enhance these transport mechanisms (2,10).
Among these, the olfactory pathway is the fastest and most efficient, while the trigeminal pathway provides access to deeper brain regions.
Intranasal drug delivery has emerged as an effective alternative to conventional routes such as oral and parenteral administration due to its unique anatomical and physiological features. The major advantages are discussed below:
The nasal cavity is highly vascularized, which facilitates rapid absorption of drugs into systemic circulation, leading to a quick onset of pharmacological action [11]. This makes it particularly useful in conditions requiring immediate therapeutic effects.
Drugs administered intranasally bypass hepatic first-pass metabolism, resulting in improved bioavailability compared to oral delivery [11]. This is especially beneficial for drugs that are extensively metabolized in the liver.
Intranasal delivery enables direct transport of drugs to the brain via olfactory and trigeminal pathways, thereby bypassing the blood–brain barrier (BBB) [6,12]. This provides a significant advantage for treating central nervous system (CNS) disorders.
The nasal route is non-invasive, painless, and does not require sterile conditions, unlike injections. It improves patient compliance and convenience, especially for long-term therapies [11].
Intranasal administration offers high bioavailability, particularly for lipophilic drugs, and can approach intravenous levels in some cases [11,13]. Additionally, the use of absorption enhancers can improve the uptake of hydrophilic drugs.
Due to efficient absorption and direct delivery, lower doses are required, which minimizes systemic side effects [11].
Intranasal delivery is suitable for small molecules, peptides, proteins, hormones, and vaccines. It is particularly advantageous for drugs that are unstable in the gastrointestinal tract [11].
It serves as a practical alternative to injections, especially for biologics like peptides and proteins, eliminating the need for trained personnel [11].
Patients can self-administer nasal formulations, improving adherence to therapy and reducing healthcare burden [11].
Intranasal delivery avoids enzymatic degradation in the gastrointestinal tract, making it suitable for acid-labile drugs [11].
Advanced systems like nanoemulsions and nanoparticles enhance drug targeting and controlled release, improving therapeutic efficacy [14,15].
The nasal cavity allows administration of only 25–200 μL per nostril, which restricts the amount of drug that can be delivered [11]. This makes it unsuitable for drugs requiring high doses.
Drugs with high molecular weight (>1 kDa) show poor permeability across the nasal mucosa, limiting the delivery of peptides and proteins without enhancers [11].
The nasal cavity possesses a mucociliary clearance mechanism, which rapidly removes drug particles from the nasal surface, thereby reducing residence time and absorption efficiency [4].
The nasal mucosa contains metabolic enzymes that can degrade drugs before they reach systemic circulation, leading to reduced bioavailability [11].
Certain drugs and excipients (e.g., absorption enhancers, surfactants) may cause nasal irritation, mucosal damage, or toxicity, especially with repeated administration [11,16]. Additionally, cosurfactants used in formulations like microemulsions may exhibit irritant properties [16].
Nasal conditions such as rhinitis, nasal congestion, and allergic reactions can significantly alter drug absorption and therapeutic outcomes [11].
Compared to the gastrointestinal tract, the nasal cavity has a relatively smaller absorptive surface area, which may limit drug absorption [11].
There is significant inter-individual and interspecies variability in nasal absorption due to differences in nasal physiology, mucus composition, and enzyme activity [11].
Due to mucus turnover and ciliary movement, drugs are quickly cleared from the nasal cavity, reducing their therapeutic effectiveness [4].
Developing effective nasal formulations is complex and requires suitable particle size, optimal viscosity, stability during storage, and the use of safe excipients. Advanced systems like nanoemulsions, microemulsions, and nanoparticles are often needed to enhance drug delivery [4,17].
Formulations such as microemulsions require careful optimization because stability depends on temperature and composition, and additives may alter system behavior [16].
Despite progress, nose-to-brain transport pathways (olfactory and trigeminal routes) are not fully understood, which limits optimization of delivery systems [4,17].
Chronic use of intranasal formulations may lead to mucosal damage, alteration of nasal physiology, and potential systemic toxicity [11,18].
Advanced delivery systems like nanoparticles and lipid carriers face manufacturing complexity, stability issues, and scale-up difficulties [18].
6.1 Overview of Nanomedicine in Intranasal Delivery
Nanomedicine has emerged as a promising strategy to enhance the efficiency of nose-to-brain drug delivery. Conventional drug delivery systems are often limited by physiological barriers such as the blood–brain barrier (BBB), enzymatic degradation, and poor permeability across biological membranes. Nanocarrier-based systems overcome these limitations by improving drug stability, bioavailability, and targeting efficiency [2-20].
Nanocarriers significantly enhance brain targeting by facilitating direct transport through olfactory and trigeminal pathways. These systems enable higher drug accumulation in the brain while reducing systemic exposure.
Polymeric nanoparticles, particularly chitosan-based systems, have demonstrated increased brain-to-blood ratios and improved nasal bioavailability [10]. Additionally, studies on intranasal delivery of neuropeptides such as oxytocin indicate that a substantial fraction of the administered dose reaches the brain directly from the nasal cavity [19,20,22].
Nanocarriers play a crucial role in protecting drugs from enzymatic degradation within the nasal cavity and during transport. Encapsulation of drugs within nanoparticles shields them from metabolic enzymes present in the nasal mucosa [6,2,20].
Furthermore, nanomedicine can help overcome efflux transporters such as P-glycoprotein, which limit drug accumulation in the brain. By enhancing drug retention and transport, nanocarriers improve therapeutic efficacy [2,20].
Nanoparticles enhance drug permeation across the nasal epithelium through mechanisms such as:
Mucoadhesive polymers such as chitosan can transiently open tight junctions, thereby improving paracellular transport. Their positive charge facilitates interaction with negatively charged mucosal surfaces, enhancing drug absorption [10,6,20].
Rapid mucociliary clearance is a major limitation of intranasal drug delivery. Nanomedicine addresses this issue by incorporating mucoadhesive materials that increase nasal residence time.
Polymers such as chitosan improve adhesion to the nasal mucosa, thereby prolonging drug retention and enhancing absorption [11,6,20].
Nanocarriers enable controlled and sustained drug release, maintaining therapeutic drug levels in the brain over extended periods. This reduces dosing frequency and improves patient compliance, particularly in chronic neurological disorders [2,20].
Systems such as liposomes, solid lipid nanoparticles, and polymeric nanoparticles provide sustained release profiles, ensuring prolonged therapeutic action [6,20].
Nanomedicine improves the safety profile of drugs by reducing systemic distribution and focusing drug delivery to the brain. This targeted approach minimizes peripheral side effects and reduces the required therapeutic dose [2,21,20].
Improved biodistribution and reduced clearance of nanoparticles further contribute to enhanced therapeutic outcomes [21].
Nanocarriers can deliver a wide range of therapeutic agents, including:
For example, intranasal delivery of oxytocin has demonstrated significant brain uptake and therapeutic potential in neurological conditions, highlighting the versatility of nanomedicine [22,20].
Nanomedicine plays a central role in improving nose-to-brain drug delivery by:
Nanocarriers have emerged as an effective strategy to enhance drug delivery from the nasal cavity to the brain by improving drug stability, permeability, and bioavailability while bypassing the blood–brain barrier (BBB). Various nanocarrier systems have been explored and can be classified as follows:
Solid lipid nanoparticles are composed of solid lipids and are widely used due to their biocompatibility, controlled drug release, and protection of drugs from enzymatic degradation. They enhance drug transport across nasal mucosa and improve brain targeting efficiency (23).
NLCs are an advanced form of SLNs containing a mixture of solid and liquid lipids, offering higher drug loading capacity and reduced drug expulsion during storage. They significantly improve drug permeability and targeting through the intranasal route (24).
Nanoemulsions are oil-in-water or water-in-oil systems with nanoscale droplets that provide enhanced solubility, rapid absorption, and improved bioavailability. They are particularly effective for delivering poorly soluble drugs and avoiding enzymatic degradation (25,26].
Polymeric nanoparticles are made from biodegradable polymers and provide controlled drug release, improved stability, and enhanced penetration through nasal epithelium. They also allow surface modification for targeted delivery to the brain (27).
Liposomes are vesicular systems composed of phospholipid bilayers capable of encapsulating both hydrophilic and lipophilic drugs. They offer high biocompatibility, targeted delivery, and enhanced nasal residence time, making them promising carriers for nose-to-brain transport (28).
Dendrimers are highly branched, nanosized polymers with controlled architecture. They provide high drug loading capacity, improved permeability, and precise targeting capabilities, making them suitable for CNS drug delivery (25).
Micelles are self-assembled colloidal systems formed by amphiphilic molecules. They enhance solubility of hydrophobic drugs and improve transport across nasal mucosa, facilitating brain delivery (28).
This includes various inorganic and organic nanoparticles (e.g., gold nanoparticles, carbon-based nanocarriers). These systems improve drug stability, targeting efficiency, and penetration through biological barriers (29).
Exosomes are naturally derived vesicles that act as biological nanocarriers. They exhibit excellent biocompatibility, low immunogenicity, and efficient transport across biological barriers, making them promising for brain targeting (29).
Microspheres and carbon-based systems (e.g., carbon nanotubes) have also been investigated for intranasal delivery due to their controlled release properties and ability to enhance drug transport to the brain (25).
Intranasal drug delivery has emerged as a promising non-invasive strategy for targeting the brain, especially for neurological and psychiatric disorders, by bypassing the blood–brain barrier (BBB) and enhancing drug bioavailability (25,30).
Alzheimer’s Disease (AD)
Intranasal delivery is extensively studied for AD due to its ability to deliver drugs directly to the brain and improve therapeutic efficacy.
Evidence:
Parkinson’s Disease (PD)
Evidence:
Other Neurodegenerative Disorders
Includes:
Evidence:
Intranasal delivery is beneficial for a wide range of CNS diseases:
Key Advantages:
Evidence:
Intranasal nanocarriers are increasingly used for treating psychiatric conditions:
Schizophrenia
Depression
Anxiety Disorders
Bipolar Disorder
Evidence:
Across all disorders, intranasal delivery offers:
Evidence:
Recent years have witnessed significant advancements in intranasal (nose-to-brain) drug delivery systems, primarily driven by the need to overcome the blood–brain barrier (BBB) and improve therapeutic outcomes in central nervous system (CNS) disorders (35,36).
One of the most important advances is the development of nanocarrier-based systems, including liposomes, polymeric nanoparticles, solid lipid nanoparticles, nanoemulsions, and nanogels. These systems enhance drug stability, targeting efficiency, and controlled release (36).
Nanoparticles also allow surface modification and ligand attachment, enabling receptor-mediated transport across the nasal epithelium and improved brain targeting. Additionally, nanocarriers protect drugs from enzymatic degradation and enhance bioavailability (36].
Similarly, recent work highlights the use of surface-functionalized and stimuli-responsive nanoparticles to improve mucosal deposition and transport efficiency, representing a major innovation in formulation strategies (37).
Modern formulations such as in situ gels, mucoadhesive systems, and nanoemulsions have been developed to overcome limitations like mucociliary clearance.
These approaches significantly improve drug absorption and sustained release (3).
Recent advances emphasize targeted delivery to the olfactory epithelium, which provides direct access to the brain.
This represents a shift toward site-specific delivery, improving therapeutic efficiency (37).
Modern research has expanded knowledge of transport pathways:
This improved mechanistic understanding supports better formulation design (35).
Recent advancements focus on optimizing:
Such optimization enhances drug permeability and bioavailability while reducing irritation and degradation (35).
Intranasal delivery has progressed from experimental research to clinical relevance, offering a non-invasive alternative for CNS drug delivery (37).
Intranasal drug delivery is being explored for treating:
Nanoparticle-based systems have shown improved drug accumulation in brain tissues, enhancing therapeutic outcomes (36).
Clinical progress shows:
These benefits make intranasal delivery a promising approach for chronic and acute CNS conditions (36).
Despite progress, several barriers remain:
These challenges highlight the gap between preclinical success and large-scale clinical application (37).
The clinical translation of intranasal (nose-to-brain) drug delivery systems is hindered by multiple physiological, formulation, and translational barriers despite promising preclinical outcomes.
One of the primary challenges is the presence of physiological barriers, including the blood–brain barrier (BBB), blood–cerebrospinal fluid barrier (BCFB), and efflux transport systems, which restrict drug penetration into the central nervous system (CNS) (38). Additionally, P-glycoprotein efflux pumps in the olfactory epithelium further limit drug accumulation in the brain, reducing therapeutic efficiency (38).
Another significant limitation is mucociliary clearance and low residence time, where the mucus layer and ciliary movement rapidly remove administered drugs from the nasal cavity, thereby decreasing drug absorption and bioavailability (38,39). This rapid clearance makes it difficult to maintain sufficient drug concentration for effective brain targeting.
The limited dosing volume of the nasal cavity (approximately 25–200 µL) also restricts the amount of drug that can be administered, posing a challenge for drugs requiring higher therapeutic doses (38). Furthermore, high drug concentrations may lead to local irritation or damage to the nasal mucosa, affecting patient safety and compliance (40).
Drug-related factors such as molecular weight, solubility, and chemical form also significantly influence nasal absorption. Drugs with high molecular weight (>1000 Da) show poor permeability, limiting their clinical applicability without the use of absorption enhancers (40). Similarly, formulation parameters like viscosity, pH, and particle size critically affect drug deposition and absorption (39).
Another key translational challenge is the complex nasal anatomy and variability in deposition, which makes it difficult to achieve targeted delivery to the olfactory region—the primary pathway for direct brain transport (37). Most formulations tend to deposit in the anterior nasal region, leading to systemic absorption rather than direct brain delivery (37).
Additionally, device-related limitations and aerodynamic barriers further complicate efficient drug delivery. The narrow nasal valve, airflow dynamics, and filtration mechanisms of the nasal cavity significantly reduce drug deposition efficiency (41). These anatomical and physiological features, while protective, act as major obstacles to consistent drug delivery.
A major issue in clinical translation is the lack of sufficient clinical studies and toxicity data, which limits regulatory approval and commercialization (40). Moreover, differences between preclinical models and human nasal physiology contribute to poor predictability of clinical outcomes (37).
The future of intranasal (nose-to-brain) drug delivery is highly promising, with increasing interest in expanding its applications beyond conventional therapies. The nasal route is expected to play a significant role as a non-invasive alternative for systemic and central nervous system (CNS) drug delivery, owing to its rapid absorption and ability to bypass first-pass metabolism [42].
One of the key future directions is the development of advanced formulations and nanocarrier-based systems. Nanoparticles, nanoemulsions, and lipid-based carriers are anticipated to improve drug stability, enhance permeability, and enable targeted delivery to the brain. These systems are expected to significantly enhance therapeutic efficacy, particularly for CNS disorders [38].
Another important perspective is the advancement of nasal dosage forms, especially the shift from conventional liquid formulations to nasal powders, which offer improved stability and better drug retention. Future developments will focus on optimizing formulation parameters such as viscosity, pH, and osmolarity to enhance drug absorption and deposition [39].
The development of innovative and patient-friendly delivery devices is also expected to play a crucial role. Future nasal devices will be more sophisticated, providing accurate dosing, improved deposition to specific nasal regions, and reduced user variability, thereby improving therapeutic outcomes [39].
Additionally, intranasal delivery is anticipated to become a major platform for vaccination and immunotherapy. The nasal mucosa, rich in immune cells, makes it an ideal site for inducing both systemic and mucosal immune responses. Future research suggests that intranasal administration may become a standard route for vaccines and booster immunizations due to its ease of administration and effectiveness [39].
Another emerging perspective is the development of personalized and precision-based delivery systems, including patient-specific nasal models and advanced imaging-guided delivery. These approaches aim to improve drug targeting to the olfactory region and enhance reproducibility in clinical outcomes [37].
Finally, future progress will depend on improved clinical studies, safety evaluation, and translational research. There is a need for more comprehensive pharmacokinetic, pharmacodynamic, and toxicological studies to ensure safe and effective clinical application. Bridging the gap between preclinical and clinical outcomes will be essential for successful commercialization [40].
Delivering drugs effectively to the brain has long been a major challenge in managing central nervous system (CNS) disorders. The performance of many CNS therapeutics is often compromised by physiological barriers such as the first-pass effect, enzymatic breakdown, the restrictive nature of the blood–brain barrier (BBB), poor cerebral blood flow, rapid systemic elimination, unwanted peripheral effects, and overall low bioavailability. The intranasal route has emerged as a promising alternative because it can bypass several of these limitations. Compared to oral and parenteral methods, it offers a non-invasive approach with the potential for more direct drug transport to the brain. To enhance its effectiveness, researchers are exploring advanced strategies such as ligand-based targeting, nanoparticle-based carriers, and mucoadhesive delivery systems, all aimed at improving drug retention and minimizing toxicity. Despite encouraging progress, most research in this field remains at the preclinical or early clinical stage, with many positive outcomes demonstrated primarily in animal models. Only a limited number of studies have progressed to human trials so far. Nevertheless, ongoing research suggests that intranasal delivery could become a viable and innovative approach for brain-targeted therapies in the future. A wide range of therapeutic agents—including small molecules, proteins, peptides, biologics, and even cells—are currently being investigated for this route, and successful clinical validation could make it a transformative option for treating neurological disorders.
REFERENCES
Chaitali More, Arundhati Pawar, Divya Ugile, Sayli Patil, Avinash Hosmani, Intranasal Nanomedicine: Emerging Routes for Direct Nose-to-Brain Delivery in Neurological and Psychiatric Disorders, Int. J. of Pharm. Sci., 2026, Vol 4, Issue 5, 5538-5556. https://doi.org/10.5281/zenodo.20326869
10.5281/zenodo.20326869