Nasal Delivery System Research Articles

Research progress in brain-targeted nasal drug delivery.

The unique anatomical and physiological connections between the nasal cavity and brain provide a pathway for bypassing the blood-brain barrier to allow for direct brain-targeted drug delivery through nasal administration. There are several advantages of nasal administration compared with other routes; for example, the first-pass effect that leads to the metabolism of orally administered drugs can be bypassed, and the poor compliance associated with injections can be minimized. Nasal administration can also help maximize brain-targeted drug delivery, allowing for high pharmacological activity at lower drug dosages, thereby minimizing the likelihood of adverse effects and providing a highly promising drug delivery pathway for the treatment of central nervous system diseases. The aim of this review article was to briefly describe the physiological structures of the nasal cavity and brain, the pathways through which drugs can enter the brain through the nose, the factors affecting brain-targeted nasal drug delivery, methods to improve brain-targeted nasal drug delivery systems through the application of related biomaterials, common experimental methods used in intranasal drug delivery research, and the current limitations of such approaches, providing a solid foundation for further in-depth research on intranasal brain-targeted drug delivery systems (see Graphical Abstract).

Design and Characterization of pH Dependent Phase Transition System of Almotriptan Malate for Nasal Drug Delivery System by Employing Factorial Design

Design and Characterization of pH Dependent Phase Transition System of Almotriptan Malate for Nasal Drug Delivery System by Employing Factorial Design

Evaluation of nasal delivery systems of olanzapine by desorption electrospray ionization mass spectrometry imaging

Nose-to-brain delivery presents an attractive administration route for neuroactive drugs that suffer from compromised bioavailability or fail to pass the blood–brain barrier. However, the conventional gauge of effectiveness for intranasal delivery platforms primarily involves detecting the presence of the administered drug within the brain, with little insight into its precise localization within brain structures. This may undermine the therapeutic efficacy of drugs and hinder the design of systems that target specific brain regions. In this study, we designed two intranasal delivery systems for the antipsychotic drug, olanzapine, and evaluated its distribution in the rat brain following intranasal administration. The first evaluated system was an olanzapine-loaded microemulsion and the second one was nanoparticulate aqueous dispersion of olanzapine. Both systems exhibited characteristics that render them compatible for intranasal administration, and successfully delivered olanzapine to the brain. We further employed an ambient mass spectrometry imaging method, called desorption electrospray ionization mass spectrometry imaging, to visualize the signal intensity of olanzapine in different brain regions following the intranasal administration of these two systems. Substantial variations in the distribution patterns of olanzapine across various brain structures were revealed, potentially highlighting the importance of mass spectrometry imaging in designing and evaluating intranasal drug delivery platforms.

Biopolymer Aerogels as Nasal Drug Delivery Systems

Biopolymer Aerogels as Nasal Drug Delivery Systems

Bi-directional nasal drug delivery systems: A scoping review of nasal particle deposition patterns and clinical application.

To compare the deposition patterns within the nasal cavity between the bi-directional and unilateral nasal delivery systems. And to summarize the clinical application of the bi-directional nasal drug delivery devices. PubMed, Cochrane Library, Embase, and Web of Science databases. A scoping review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). We included studies exploring patterns and influencing factors of particle depositions within the nasal cavity among patients, healthy controls, and nose cast models using the bi-directional and unilateral nasal delivery system. The clinical application of the bi-directional delivery devices was also summarized. A total of 24 studies were included in this review. Bi-directional nasal delivery systems utilize forced exhalation to power the delivery of drugs to deeper areas of the nasal cavity and paranasal sinuses. Unilateral nasal delivery systems included traditional liquid spray pumps, the aerosol mask system, nebulization, and conventional nasal inhalation. Compared with unilateral delivery systems, the bi-directional nasal delivery system provided a more extensive and efficient nasal deposition in the nasal cavity, especially in the olfactory cleft, without lung deposition. Several parameters, including particle size, pulsatile flow, and nasal geometry, could significantly influence nasal deposition. The bi-directional nasal delivery system enables better delivery of steroids or sumatriptan to the sinonasal cavity's high and deep target sites. This bi-directional delivery device demonstrated an effective and well-tolerated treatment that produced high drug utilization, rapid absorption, and sustained symptom improvement among patients with chronic rhinosinusitis (CRS) or migraine. The bi-directional nasal drug delivery systems demonstrated significantly higher drug deposition in superior and posterior regions of the nasal cavity than unilateral nasal delivery systems. Further studies should explore its potential role in delivering drugs to the olfactory cleft among patients with olfactory disorders and central nervous system diseases. N/A.

A Review on Nasal Self-Emulsifying Drug Delivery Systems: An Alternative Approach to Improve Brain Bioavailability of Poorly Water-Soluble Drugs

Neurotherapeutic drugs fail to reach the site of action due to poor bioavailability, poor water solubility, limited permeability, hepatic first-pass metabolism, and the blood-brain barrier. The nasal cavity allows drugs to be delivered directly to the brain, bypassing the blood-brain barrier. The nasal cavity also avoids hepatic first-pass metabolism, enhancing the systemic bioavailability of highly metabolized substances. As a result, most neurotherapeutics have physicochemical properties that necessitate their formulation in lipidic nanosystems as self-emulsifying drug delivery systems (SEDDS). These are isotropic mixes of oils, surfactants, and co-surfactants that, when diluted in water, produce micro or nanoemulsions containing high quantities of lipophilic medicines. SEDDS should prevent drug precipitation at absorption sites, boost permeability through absorptive membranes, and improve labile drug stability against enzymatic activity. When the benefits of SEDDS and the intranasal route for brain delivery are combined, an increase in medication brain targeting and bioavailability might be expected.

Development of Vinpocetine-Loaded Nasal Polymeric Micelles via Nano-Spray-Drying.

In this present formulation study, vinpocetine-loaded nano-spray-dried polymeric micelles were developed via nano-spray-drying. Three different mucoadhesive excipients were applied in the studies, namely chitosan, hyaluronic acid and hydroxypropyl methylcellulose. In all cases, the formulations had a proper particle size and drug content after drying with spherical morphology and amorphous structure. After rapid dissolution in water, the polymeric micelles had a particle size around 100-130 nm, in monodisperse size distribution. The high encapsulation efficiency (>80%) and high solubilization (approx. 300-fold increase in thermodynamic solubility) contributed to rapid drug release (>80% in the first 15 min) and fast passive diffusion at simulated nasal conditions. The formulated prototype preparations fulfilled the demands of a low-viscosity, moderately mucoadhesive nasal drug delivery system, which may be capable of increasing the overall bioavailability of drugs administered via the auspicious nasal drug delivery route.

Lipid-based nanoparticles via nose-to-brain delivery: a mini review.

Central nervous system disorders significantly affect the lives and health of millions of people worldwide. Despite many therapeutic drugs are available that could potentially target central nervous system disorders, their clinical utility is severely constrained by their inability to cross the blood-brain barrier (BBB). Fortunately, nanotechnology has been advanced to offers a solution to allow drugs reaching the targeted brain regions safely, efficiently, and precisely through nasal drug delivery system (NDDS), bypassing the BBB completely. This strategy can promote the drug accumulated in the targeted brain region, improve drug bioavailability, and minimal side effects and mucociliary clearance effectively. In this review, we elaborate recent advances in the use of lipid-based nanoparticles, involving liposomes, nanoemulsions, nanostructured lipid carriers, and solid lipid nanoparticles. Besides, we particularly introduced the nasal cavity physiological structure, and further summarized the nose-to-brain drug delivery pathways, including olfactory, trigeminal, and blood circulation pathway. Moreover, the mechanism and route of NDDS by various types of nanoparticles are also highlighted.

Effective nose-to-brain drug delivery using a combination system targeting the olfactory region in monkeys

The nose-to-brain (N2B) pathway has garnered attention because it transports drugs directly into the brain. Although recent studies have suggested the necessity of selective drug administration to the olfactory region for effective N2B drug delivery, the importance of delivering the formulation to the olfactory region and the detailed pathway involved in drug uptake in primates brain remain unclear. Here, we developed a combination system for N2B drug delivery comprising a proprietary mucoadhesive powder formulation and a dedicated nasal device (N2B-system) and evaluated it for nasal drug delivery to the brain in cynomolgus monkeys. This N2B-system demonstrated a much greater formulation distribution ratio in the olfactory region in an in vitro experiment using a 3D-printed nasal cast and in vivo experiment using cynomolgus monkeys, as compared to that in other nasal drug delivery systems that comprise of a proprietary nasal powder device developed for nasal absorption and vaccination and a commercially available liquid spray. Additionally, Texas Red-labeled dextran (TR-DEX, 3 kDa) was administered using the N2B-system to estimate the drug transition pathway from the nasal cavity to the brain. TR-DEX preferentially localized to the olfactory epithelium and reached the olfactory bulb through the cribriform foramina. Moreover, domperidone, a model drug with poor blood-brain barrier permeability, was administered to assess the brain uptake of medicine after olfactory region-selective administration by using the N2B-system. Domperidone accumulation in the brain was evaluated using positron emission tomography with intravenously administered [18F]fallypride based on competitive inhibition of the dopamine D2 receptor (D2R). Compared to other systems, the N2B-system significantly increased D2R occupancy and domperidone uptake in the D2R-expressing brain regions. The current study reveals that the olfactory region of the nasal cavity is a suitable target for efficient nasal drug delivery to the brain in cynomolgus monkeys. Thus, the N2B-system, which targets the olfactory region, provides an efficient approach for developing effective technology for nasal drug delivery to the brain in humans.

Biodistribution assessment of cationic pullulan nanogel, a nasal vaccine delivery system, in mice and non-human primates

Cationic cholesteryl-group–bearing pullulan nanogel (cCHP-nanogel) is an effective drug-delivery system for nasal vaccines. However, cCHP-nanogel-based nasal vaccines might access the central nervous system due to its close proximity via the olfactory bulb in the nasal cavity. Using real-time quantitative tracking of the nanogel-based nasal botulinum neurotoxin and pneumococcal vaccines, we previously confirmed the lack of deposition of vaccine antigen in the cerebrum or olfactory bulbs of mice and non-human primates (NHPs), rhesus macaques. Here, we used positron emission tomography to investigate the biodistribution of the drug-delivery system itself, cCHP-nanogel after mice and NHPs were nasally administered with 18F-labeled cCHP nanogel. The results generated by the PET analysis of rhesus macaques were consistent with the direct counting of radioactivity due to 18F or 111In in dissected mouse tissues. Thus, no depositions of cCHP-nanogel were noted in the cerebrum, olfactory bulbs, or eyes of both species after nasal administration of the radiolabeled cCHP-nanogel compound. Our findings confirm the safe biodistribution of the cCHP-nanogel-based nasal vaccine delivery system in mice and NHPs.

Visualization of nasal powder distribution using biomimetic human nasal cavity model

Nasal drug delivery efficiency is highly dependent on the position in which the drug is deposited in the nasal cavity. However, no reliable method is currently available to assess its impact on delivery performance. In this study, a biomimetic nasal model based on three-dimensional (3D) reconstruction and three-dimensional printing (3DP) technology was developed for visualizing the deposition of drug powders in the nasal cavity. The results showed significant differences in cavity area and volume and powder distribution in the anterior part of the biomimetic nasal model of Chinese males and females. The nasal cavity model was modified with dimethicone and validated to be suitable for the deposition test. The experimental device produced the most satisfactory results with five spray times. Furthermore, particle sizes and spray angles were found to significantly affect the experimental device's performance and alter drug distribution, respectively. Additionally, mometasone furoate (MF) nasal spray (NS) distribution patterns were investigated in a goat nasal cavity model and three male goat noses, confirming the in vitro and in vivo correlation. In conclusion, the developed human nasal structure biomimetic device has the potential to be a valuable tool for assessing nasal drug delivery system deposition and distribution.

Unraveling the role of chitosan for nasal drug delivery systems: A review

The discipline of nanoscience has made enormous strides in the recent two decades. The researchers in the field of nanomedicine have been looking into using natural biodegradable polymeric nano-colloids for targeted drug delivery, due to their high levels of bioavailability, biocompatibility, enhanced permeability, better retention time, safety, and less toxicity. The nasal cavity has been considered as an efficient route with great potential for the management of local and systemic diseases like asthma, pneumonia, Alzheimer's disease, etc. Chitosan (CS), a natural polymer, along with its greater efficacy and less toxicity, makes it an attractive candidate for nasal administration. This review has focused on the limitations that might arise when using the nasal route and how CS can play a mechanistic role in helping with these complications when using the nasal drug delivery system. The major revelation from this article is to summarize the various formulations and innovation of CS-loaded nano colloids, such as nanoparticles, liposomes, hydrogels, in situ gel, etc. The preclinical study and various patents published also concluded that the intranasal delivery of CS-loaded nanocolloids have wide potential to manage various neurodegenerative, respiratory, cardiovascular, etc. disorders.

High-flow nasal oxygen vs. standard oxygen therapy for patients undergoing transcatheter aortic valve replacement with conscious sedation: a randomised controlled trial

BackgroundMinimally invasive surgery is becoming more common and transfemoral transcatheter aortic valve replacement is offered to older patients with multiple comorbidities. Sternotomy is not required but patients must lie flat and still for up to 2–3 h. This procedure is increasingly being performed under conscious sedation with supplementary oxygen, but hypoxia and agitation are commonly observed.MethodsIn this randomised controlled trial, we hypothesised that high-flow nasal oxygen would provide superior oxygenation as compared with our standard practice, 2 l min−1 oxygen by dry nasal specs. This was administered using the Optiflow THRIVE Nasal High Flow delivery system (Fisher and Paykel, Auckland, New Zealand) at a flow rate of 50 l min−1 and FiO2 0.3. The primary endpoint was the change in arterial partial pressure of oxygen (pO2) during the procedure. Secondary outcomes included the incidence of oxygen desaturation, airway interventions, the number of times the patient reached for the oxygen delivery device, incidence of cerebral desaturation, peri-operative oxygen therapy duration, hospital length of stay and patient satisfaction scores.ResultsA total of 72 patients were recruited. There was no difference in change in pO2 from baseline using high-flow compared with standard oxygen therapy: median [IQR] increase from 12.10 (10.05–15.22 [7.2–29.8]) to 13.69 (10.85–18.38 [8.5–32.3]) kPa vs. decrease from 15.45 (12.17–19.33 [9.2–22.8]) to 14.20 (11.80–19.40 [9.7–35.1]) kPa, respectively. The percentage change in pO2 after 30 min was also not significantly different between the two groups (p = 0.171). There was a lower incidence of oxygen desaturation in the high-flow group (p = 0.027). Patients in the high-flow group assigned a significantly higher comfort score to their treatment (p ≤ 0.001).ConclusionThis study has demonstrated that high flow, compared with standard oxygen therapy, does not improve arterial oxygenation over the course of the procedure. There are suggestions that it may improve the secondary outcomes studied.Trial registrationInternational Standard Randomised Controlled Trial Number (ISRCTN) 13,804,861. Registered on 15 April 2019. https://doi.org/10.1186/ISRCTN13804861

Computational optimization of delivery parameters to guide the development of targeted Nasal spray

Airborne transmission by droplets and aerosols is known to play a critical role in the spread of many viruses amongst which are the common flu and the more recent SARS-CoV-2 viruses. In the case of SARS-CoV-2, the nasal cavity not only constitutes an important viral entry point, but also a primary site of infection (Sungnak W. et al. Nat. Med. 26:681–687. https://doi.org/10.1038/s41591-020-0868-6, 2020).. Although face masks are a well-established preventive measure, development of novel and easy-to-use prophylactic measures would be highly beneficial in fighting viral spread and the subsequent emergence of variants of concern (Tao K. et al. Nat Rev Genet 22:757–773. https://doi.org/10.1038/s41576-021-00408-x, 2021). Our group has been working on optimizing a nasal spray delivery system that deposits particles inside the susceptible regions of the nasal cavity to act as a mechanical barrier to impede viral entry. Here, we identify computationally the delivery parameters that maximize the protection offered by this barrier. We introduce the computational approach and quantify the protection rate obtained as a function of a broad range of delivery parameters. We also introduce a modified design and demonstrate that it significantly improves deposition, thus constituting a viable approach to protect against nasal infection of airborne viruses. We then discuss our findings and the implications of this novel system on the prevention of respiratory diseases and targeted drug delivery.

INCOVACC COVID-19 vaccine: A Twitter based Social Media Analysis Using Natural Language Processing, Sentiment Analysis, and Topic Modelling

Most, if not all, the vaccine candidates designed to counteract COVID-19 due to SARS-CoV-2 infection require parenteral administration. Mucosal immunity established by vaccination could significantly contribute to containing the SARS-CoV-2 pandemic, which is spread by infected respiratory secretions. The world has been impacted on many fronts by the COVID-19 pandemic since early 2020 and has yet to recover entirely from the impact of the crisis. In late 2022 and early 2023, China experienced a new surge of COVID-19 outbreaks, mainly in the country's northeastern region. With the threat of new variants like XBB 1.5 and BF.7, India might experience a similar COVID-19 surge as China and needs to be prepared to avoid destruction again. An intranasal vaccine can elicit multiple immunological responses, including IgG neutralization, mucosal IgA production, and T-cell responses. In order to prevent further infection and the spread of COVID-19, local immune responses in the nasal mucosa are required. iNCOVACC is a recombinant vaccine vectored by an adenovirus that contains a SARS-CoV-2 spike protein that has been pre-fusion stabilized. This vaccine candidate has shown promise in both early and late-stage clinical trials. iNCOVACC has been designed for intranasal administration via nasal drops. The nasal delivery system was created to reduce expenses for those living in poor and moderate-income countries. The newly introduced intranasal COVID vaccine will be beneficial in mass immunizing the public as it does not need any syringe and can be proven to be an effective method to boost immunity against the SARS-CoV-2 virus. This study uses natural language processing (NLP) techniques to analyze the Indian citizen's perceptions of the newly developed iNCOVACC vaccine in social media. For this study, we have used social media posts (tweets) as data. We have analyzed 125,300 tweets to study the general perception of Indian citizens regarding the iNCOVACC vaccine. Our results have indicated 43.19% of social media posts discussing the COVID-19 nasal vaccine in a neutral tone, nearly 34.29% of social media posts are positive, and 22.5% of social media posts discussions are negative. The general positive feeling that the iNCOVACC vaccine will work and the risks in the new vaccine are the two significant aspects Indian citizens voice out in social media posts about the iNCOVACC vaccine.

Emerging Trends and Future Challenges of Nanovaccine Delivery via Nasal Route.

The mucosal surfaces are the key site of the entrance, protection, and stability of several pathogens. Considering that >90% of pathogens gain access to the body via mucosal sites, using mucosal vaccination to generate protective immunity at mucosal sites could overcome. Some of the micro and nano carrier-based nasal delivery systems produce cellular, humoral and mucosal immunity. The nasal route vaccination may protect multiple distant mucosal sites like-rectal, vaginal, oral, and pulmonary. Also, it is a convenient and cost-effective vaccination mode with improved patient compliance. Several nasal vaccine delivery systems are currently being supplied in the form of liposomes, micro/nano particulates, which have shown immunity in animal models. Especially particulate nanovaccine has a special character related to long-term immunogenicity and high efficiency. The significance and the ability of the nasal route vaccination programs are unexplained and complications; therefore, effective delivery strategies will promote the production of nasal vaccines. The present study focuses on vaccine delivery strategies and their effects on the immune system. Also, the study discusses the benefits of mucosal-associated immune response over the conventional delivery system for vaccine via the nasal route.

Nasal vaccines: solutions for respiratory infectious diseases.

Nasal vaccines induce pathogen-specific dual protective immunity at mucosal surfaces and systemically throughout the body. Consequently, nasal vaccines both prevent pathogen invasion and reduce disease severity. Because of these features, nasal vaccines are considered to be a next-generation tool for preventing respiratory infectious diseases, including COVID-19. However, nasal vaccines must overcome key safety concerns given the anatomic proximity of the central nervous system (CNS) via the olfactory bulbs which lie next to the nasal cavity. This review summarizes current efforts to develop safe and effective nasal vaccines and delivery systems, as well as their clinical applications for the prevention of respiratory infections. We also discuss various concerns regarding the safety of nasal vaccines and introduce a system for evaluating them.

Statistically Optimized Facile Development, Characterization and Evaluation of Niosomal Nasal Drug Delivery System of Ropinirole Hydrochloride: In vitro Drug Release, Cytotoxicity and ex vivo Permeability Studies

Abstract: Introduction: Nasal route is an alluring route for direct drug delivery to the central nervous system (CNS), owing to its avoidance of the hepatic first-pass metabolism and deciphering the blood–brain barrier passage issues. ROP-HCl has a lower experimental BBB permeability therefore ROP-HCl freighted niosomes were fabricated by ethanol injection method and served two purposes one being a novel Niosomal formulation impacting the permeability and other obtaining a sustained release property which likely would lead to an improved bioavailability of ROP-HCl. Objectives: The present study is aimed to develop a stable non-ionic surfactant vesicle; Niosomes embodying Ropinarole Hydrochloride (ROP-HCl) for ameliorated treatment of Parkinson’s disease (PD) by statistical optimization employing a 3-level factorial design using Design Expert® software. Materials and Methods: All the formulations were characterized physiochemically and morphologically. Additionally, the drug and excipients interaction studies were evaluated using Differential scanning calorimetry (DSC), X-ray diffraction (XRD) and Fourier-transform infrared spectroscopy (FTIR). Further, in vitro release kinetics using DD solver excel add-in and mechanism was studied for developed Niosomal formulation. Cytotoxicity study was studied in Raw 264.7 cells. in a concentration dependent manner and ex vivo, permeability was done using sheep mucosa. Toxicity was studied by histological examination. Results: The IC50 value of developed Niosomes was lower than drug itself and further the permeability of developed Niosomes was considerably enhanced compared to ROP-HCl alone. Histological examination revealed safe nature of developed formulation. Conclusion: These results conveyed that, Niosomes can be a valuable carrier for the nasal delivery of ROP-HCl to CNS. Keywords: Ropinirole hydrochloride, Statistical approach, Niosomes, Nasal drug delivery, cytotoxicity, Release kinetics, Ex-vivo permeability, Toxicity study.

FOCUS ON NIOSOMAL–BASED DRUG DELIVERY SYSTEMS FOR NASAL ROUTE: APPLICATIONS AND CHALLENGES

For decades, the nasal route of administration is principally used for many therapeutic applications owing to the non-invasive nature of the nasal pathway. Besides, it circumvents blood-brain-barrier (BBB) and hepatic first-pass effect. Consequently, the nasal route is much preferred over other invasive approaches like intravenous, intracerebral, and transcranial for the systemic delivery of drugs and the treatment of central nervous systems (CNS) disorders such as depression, Alzheimer’s disease (AD), multiple sclerosis, and Parkinson’s disease (PD) via the nose-to-brain pathway. Drug applied via the nasal route displays some difficulty to reach the brain, like the dose limitation of the nasal pathway, mucociliary clearance, etc. The efficiency of the nasal route depends on the application delivery system. Lipidic-based drug delivery systems (liposomes, solid lipid nanoparticles …etc.) have been confirmed for their promising impact on the nasal delivery approach. Furthermore, the sensitivity of the nasal route and the touched-complications of clinical trials in CNS disorders assigns the necessity of consideration to the clinical trials and approval process of the niosomal-based nasal drug delivery approach. This review describes different approaches to nasal delivery, lipidic-based delivery systems with a focus on niosomes as a promising nasal delivery system, along with different formulation methodologies, and applications.

Nasal Drug Delivery System and its Applicability in Therapeutics: A Review

The scientific community has been interested in nasal drug delivery as an additional method for administering vaccines and biomolecules including proteins peptides and non-peptide medications. This interest arises from the fact that unstable drugs often undergo significant breakdown in the gastrointestinal tract GIT or experience first-pass hepatic metabolism when taken orally. The nasal route on the other hand provides a convenient alternative for delivering these drugs. The nasal route offers a parenteral drug delivery option which is advantageous for long-term therapy. Due to its high vascularization and permeability the nasal mucosa promotes rapid absorption and onset of action. It is non-invasive often utilized for both local and systemic therapy and allows medication to enter the systemic circulation without any intermediate steps. Additionally this approach is employed to circumvent the blood-brain barrier BBB. While absorption promoters can enhance the absorption of large molecules like protein nucleic acid etc. nasal medication delivery provides higher absorption rates for low molecular weight pharmaceuticals. This article provides a comprehensive overview of current developments in intranasal drug delivery covering various aspects including the components involved strategies for enhancing bioavailability analysis of nasal drug formulation and factors influencing nasal absorption.