Nasal Pathway Research Articles

An Update on Recent Drug Delivery Systems Targeting Brain Diseases via the Transnasal Pathway.

To explore the potential of transnasal drug delivery systems (DDS) as an effective means of bypassing the bloodbrain barrier (BBB) for enhanced central nervous system (CNS) targeting, aiming to improve therapeutic outcomes for CNS disorders while reducing systemic side effects. A review of current and emerging DDS technologies, including polymer nanoparticles, liposomes, and micelles, was conducted to assess their suitability for precision-targeted delivery to the brain through the transnasal route. The investigated DDS demonstrate promising capabilities for CNS targeting via the nasal pathway, effectively preserving both the nasal mucosa and CNS integrity. These systems enhance drug precision within neural tissues, potentially improving therapeutic outcomes without harming adjacent tissues. Transnasal DDS offer a promising alternative to traditional delivery methods, with significant potential to advance the treatment of cerebrovascular diseases, neurodegenerative disorders, brain tumors, and psychiatric conditions. This approach represents an evolving frontier in neurotherapeutics, with the potential to transform CNS drug delivery practices.

1-11C]-Butanol Positron Emission Tomography reveals an impaired brain to nasal turbinates pathway in aging amyloid positive subjects

BackgroundReduced clearance of cerebrospinal fluid (CSF) has been suggested as a pathological feature of Alzheimer’s disease (AD). With extensive documentation in non-human mammals and contradictory human neuroimaging data it remains unknown whether the nasal mucosa is a CSF drainage site in humans. Here, we used dynamic PET with [1-11C]-Butanol, a highly permeable radiotracer with no appreciable brain binding, to test the hypothesis that tracer drainage from the nasal pathway reflects CSF drainage from brain. As a test of the hypothesis, we examined whether brain and nasal fluid drainage times were correlated and affected by brain amyloid.Methods24 cognitively normal subjects (≥ 65 years) were dynamically PET imaged for 60 min. using [1-11C]-Butanol. Imaging with either [11C]-PiB or [18F]-FBB identified 8 amyloid PET positive (Aβ+) and 16 Aβ- subjects. MRI-determined regions of interest (ROI) included: the carotid artery, the lateral orbitofrontal (LOF) brain, the cribriform plate, and an All-turbinate region comprised of the superior, middle, and inferior turbinates. The bilateral temporalis muscle and jugular veins served as control regions. Regional time-activity were used to model tracer influx, egress, and AUC.ResultsLOF and All-turbinate 60 min AUC were positively associated, thus suggesting a connection between the brain and the nose. Further, the Aβ+ subgroup demonstrated impaired tracer kinetics, marked by reduced tracer influx and slower egress.ConclusionThe data show that tracer kinetics for brain and nasal turbinates are related to each other and both reflect the amyloid status of the brain. As such, these data add to evidence that the nasal pathway is a potential CSF drainage site in humans. These data warrant further investigation of brain and nasal contributions to protein clearance in neurodegenerative disease.

Advances in Aerosol Formulation for Targeted Delivery of Therapeutic Agents from Nose to Brain.

The intricate anatomical and physiological barriers that prohibit pharmaceuticals from entering the brain continue to provide a noteworthy hurdle to the efficient distribution of medications to brain tissues. These barriers prevent the movement of active therapeutic agents into the brain. The present manuscript aims to describe the various aspects of brain-targeted drug delivery through the nasal route. The primary transport mechanism for drug absorption from the nose to the brain is the paracellular/extracellular mechanism, which allows for rapid drug transfer. The transcellular/intracellular pathway involves the transfer across a lipoidal channel, which regulates the entry or exit of anions, organic cations, and peptides. Spectroscopy and PET (positron emission tomography) are two common methods used for assessing drug distribution. MRI (Magnetic resonance imaging) is another imaging method used to assess the efficacy of aerosol drug delivery from nose to brain. It can identify emphysema, drug-induced harm, mucus discharge, oedema, and vascular remodeling. The olfactory epithelium's position in the nasal cavity makes it difficult for drugs to reach the desired target. Bi-directional aerosol systems and tools like the "OptiNose" can help decrease extranasal particle deposition and increase particle deposition efficiency in the primary nasal pathway. Direct medicine administration from N-T-B, however, can reduce the dose administered and make it easier to attain an effective concentration at the site of activity, and it has the potential to be commercialized.

High-Flow Nasal Cannula Therapy as an Adjuvant Therapy for Respiratory Support during Endoscopic Techniques: A Narrative Review.

High-flow nasal cannula (HFNC) is a respiratory support technique that delivers a controlled concentration of oxygen with high flow, heat, and humidity via the nasal pathway. As it has many physiological effects, its use has increased for a variety of clinical indications; however, there is limited guidance on using HFNC as a respiratory support tool during endoscopic procedures. We conducted a narrative review to evaluate the effect of HFNC as an adjuvant tool during fiberoptic bronchoscopy (FOB), upper gastrointestinal tract endoscopy, and surgical procedures in adults. A search of the PubMed and Cochrane databases were performed. Approximately 384 publications were retrieved, and 99 were selected (93 original works and 6 case reports with a literature review). In patients who underwent FOB, HFNC appears to be superior to conventional oxygen therapy (COT) in preventing hypoxaemia. In contrast, for gastrointestinal endoscopy, the current evidence is insufficient to recommend HFNC over COT in a cost-effective manner. Finally, in surgical procedures such as laryngeal microsurgery or thoracic surgery, HFNC has been shown to be a safe and effective alternative to orotracheal intubation. As the results are heterogeneous, we advocate for the need for more quality studies to understand the effectiveness of HFNC during endoscopic procedures.

Development and optimization of in-situ gel containing chitosan nanoparticles for possible nose-to-brain delivery of vinpocetine

Vinpocetine (VIN), a derivative of vincamine found in the vinca plant, widens blood vessels in the brain and has been shown to improve cognitive function, memory, and cerebrovascular disorders. Nevertheless, the clinical utility of VIN is constrained by factors such as low oral bioavailability owing to the first-pass metabolism that often demands frequent dosing of 3–4 tablets/day. In this regard, the present work aimed to develop VIN-loaded chitosan nanoparticles (VIN-CH-NPs) to surmount these limitations and in view to enhance delivery to the brain of VIN by minimizing systemic exposure. The chitosan (CH) nanoparticles (NP) were developed by ionotropic gelation technique employing tripolyphosphate (TPP) as a cross-linking agent. Employing Design of Experiments (DoE), the effect of CH and TPP concentrations and stirring speed were systematically optimized using Box Behnken design (BBD). The optimized batch of nanoparticles displayed a particle size, zeta potential, entrapment efficiency, and drug loading of 130.6 ± 8.38 nm, +40.81 ± 0.11 mV, 97.56 ± 0.04 %, and 61 ± 0.89 %, respectively. Fourier Transform Infrared Spectroscopy indicated the chemical integrity of the drug ruling out the interaction between the VIN and excipients used. DSC and PXRD data indicated that reduction of the crystallinity of VIN in the chitosan matrix. These VIN-CH-NPs manifested good stability, exhibiting an almost spherical morphology. To mitigate rapid mucociliary clearance upon intranasal administration, the optimized VIN-CH-NPs were incorporated into thermosensitive in situ gel (VIN-CHN-ISG). It was observed that the in-situ gel loaded with nanoparticles was opalescent with a pH level of 5.3 ± 0.38. It was also noted that the gelation temperature was 32 ± 0.89 °C, and the gelation time was approximately 15 s. The drug delivery to the brain through the nasal application of optimized VIN-NPs in situ gel was assessed in rats. The results indicated significant nasal application of the in-situ gel nearly doubled the Cmax (P < 0.05) and AUC0-t (P < 0.05) in the brain compared to oral administration. Nasal administration improved drug delivery to the brain by reducing systemic exposure to VIN. A histopathological study of the nasal mucosa revealed no irritation or toxicity, making it safe for nasal administration. These findings suggest that the developed NPs in-situ gel effectively targeted vinpocetine to the brain through the nasal pathway, providing a potential therapeutic strategy for managing Alzheimer's disease.

Pharmacokinetics of intranasal amiloride in healthy volunteers.

Anxiety and panic disorders are the most common mental illnesses in the United States and lack effective treatment options. Acid-sending ion channels (ASICs) in the brain were shown to be associated with fear conditioning and anxiety responses and therefore are potential targets for treating panic disorder. Amiloride is an inhibitor of the ASICs in the brain and was shown to reduce panic symptoms in preclinical animal models. An intranasal formulation of amiloride will be highly beneficial to treat acute panic attacks due to advantages such as the rapid onset of action and patient compliance. The aim of this single-center, open-label trial was to evaluate the basic pharmacokinetics (PKs) and safety of amiloride after intranasal administration in healthy human volunteers at three doses (0.2, 0.4, and 0.6 mg). Amiloride was detected in plasma within 10 min of intranasal administration and showed a biphasic PK profile with an initial peak within 10 min of administration followed by a second peak between 4 and 8 h of administration. The biphasic PKs indicate an initial rapid absorption via the nasal pathway and later slower absorption by non-nasal pathways. Intranasal amiloride exhibited a dose-proportional increase in the area under the curve and did not exhibit any systemic toxicity. These data indicate that intranasal amiloride is rapidly absorbed and safe at the doses evaluated and can be further considered for clinical development as a portable, rapid, noninvasive, and nonaddictive anxiolytic agent to treat acute panic attacks.

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.

Hydroxyethylcellulose-Based Hydrogels Containing Liposomes Functionalized with Cell-Penetrating Peptides for Nasal Delivery of Insulin in the Treatment of Diabetes.

Liposomes functionalized with cell-penetrating peptides are a promising strategy to deliver insulin through the nasal route. A hydrogel based on hydroxyethylcellulose (HEC) aqueous solution was prepared, followed by a subsequent addition of liposomes containing insulin solution functionalized with trans-activator of transcription protein of HIV-1 (TAT) or Penetratin (PNT). The formulations were characterized for rheological behavior, mucoadhesion, syringeability, in vitro release and in vivo efficacy. Rheological tests revealed non-Newtonian fluids with pseudoplastic behavior, and the incorporation of liposomes (HLI, HLITAT and HLIPNT) in hydrogels did not alter the behavior original pseudoplastic characteristic of the HEC hydrogel. Pseudoplastic flow behavior is a desirable property for formulations intended for the administration of drugs via the nasal route. The results of syringeability and mucoadhesive strength from HEC hydrogels suggest a viable vehicle for nasal delivery. Comparing the insulin release profile, it is observed that HI was the system that released the greatest amount while the liposomal gel promoted greater drug retention, since the liposomal system provides an extra barrier for the release through the hydrogel. Additionally, it is observed that both peptides tested had an impact on the insulin release profile, promoting a slower release, due to complexation with insulin. The in vitro release kinetics of insulin from all formulations followed Weibull's mathematical model, reaching approximately 90% of release in the formulation prepared with HEC-based hydrogels. Serum insulin levels and the antihyperglycemic effects suggested that formulations HI and HLI have potential as carriers for insulin delivery by the nasal pathway, a profile not observed when insulin was administered by subcutaneous injection or by the nasal route in saline. Furthermore, formulations functionalized with TAT and PNT can be considered promoters of late and early absorption, respectively.

Respiratory influence on brain dynamics: the preponderant role of the nasal pathway and deep slow regime.

As a possible body signal influencing brain dynamics, respiration is fundamental for perception, cognition, and emotion. The olfactory system has recently acquired its credentials by proving to be crucial in the transmission of respiratory influence on the brain via the sensitivity to nasal airflow of its receptor cells. Here, we present recent findings evidencing respiration-related activities in the brain. Then, we review the data explaining the fact that breathing is (i) nasal and (ii) being slow and deep is crucial in its ability to stimulate the olfactory system and consequently influence the brain. In conclusion, we propose a possible scenario explaining how this optimal respiratory regime can promote changes in brain dynamics of an olfacto-limbic-respiratory circuit, providing a possibility to induce calm and relaxation by coordinating breathing regime and brain state.

Utilization of Polymeric Micelles as a Lucrative Platform for Efficient Brain Deposition of Olanzapine as an Antischizophrenic Drug via Intranasal Delivery.

Schizophrenia is a mental disorder characterized by alterations in cognition, behavior and emotions. Oral olanzapine (OZ) administration is extensively metabolized (~up to 40% of the administrated dose). In addition, OZ is a P-glycoproteins substrate that impairs the blood–brain barrier (BBB) permeability. To direct OZ to the brain and to minimize its systemic side effects, the nasal pathway is recommended. OZ-loaded polymeric micelles nano-carriers were developed using suitable biodegradable excipients. The developed micelles were physicochemically investigated to assess their appropriateness for intranasal delivery and the potential of these carriers for OZ brain targeting. The selected formula will be examined in vivo for improving the anti-schizophrenic effects on a schizophrenia rat model. The binary mixture of P123/P407 has a low CMC (0.001326% w/v), which helps in maintaining the formed micelles’ stability upon dilution. The combination effect of P123, P407 and TPGS led to a decrease in micelle size, ranging between 37.5–47.55 nm and an increase in the EE% (ranging between 68.22–86.84%). The selected OZ–PM shows great stability expressed by a suitable negative charge zeta potential value (−15.11 ± 1.35 mV) and scattered non-aggregated spherical particles with a particle size range of 30–40 nm. OZ–PM maintains sustained drug release at the application site with no nasal cytotoxicity. In vivo administration of the selected OZ–PM formula reveals improved CNS targeting and anti-schizophrenia-related deficits after OZ nasal administration. Therefore, OZ–PM provided safe direct nose-to-brain transport of OZ after nasal administration with an efficient anti-schizophrenic effect.

Donepezil HCl Liposomes: Development, Characterization, Cytotoxicity, and Pharmacokinetic Study.

The current research work aims to study the pharmacokinetic and nasal ciliotoxicity of donepezil liposome-based in situ gel to treat Alzheimer's disease. The physicochemical properties and first-pass metabolism of donepezil HCl result in low concentrations reaching the brain post oral administration. To overcome this problem, donepezil HCl-loaded liposomes were formulated using the ethanol injection method. The donepezil HCl-loaded liposomes were spherical with a size of 103 ± 6.2 nm, polydispersity index of 0.108 ± 0.008, and entrapment efficiency of 93 ± 5.33 %. The optimized in situ gel with donepezil HCl-loaded liposomes showed 80.11 ± 7.77 % drug permeation than donepezil HCl solution-based in situ gel (13.12 ± 4.84 %) across sheep nasal mucosa. The nasal ciliotoxicity study indicated the safety of developed formulation for administration via nasal route. The pharmacokinetics and biodistribution study of developed formulation showed higher drug concentration (1239.61 ± 123.60 pg/g) in the brain after nasal administration indicating its better potential via the nasal pathway. To treat Alzheimer's disease, the administration of liposome-based in situ gel through the nasal pathway can therefore be considered as an effective and promising mode of drug delivery.

The Brain-Nose Interface: A Potential Cerebrospinal Fluid Clearance Site in Humans.

The human brain functions at the center of a network of systems aimed at providing a structural and immunological layer of protection. The cerebrospinal fluid (CSF) maintains a physiological homeostasis that is of paramount importance to proper neurological activity. CSF is largely produced in the choroid plexus where it is continuous with the brain extracellular fluid and circulates through the ventricles. CSF movement through the central nervous system has been extensively explored. Across numerous animal species, the involvement of various drainage pathways in CSF, including arachnoid granulations, cranial nerves, perivascular pathways, and meningeal lymphatics, has been studied. Among these, there is a proposed CSF clearance route spanning the olfactory nerve and exiting the brain at the cribriform plate and entering lymphatics. While this pathway has been demonstrated in multiple animal species, evidence of a similar CSF egress mechanism involving the nasal cavity in humans remains poorly consolidated. This review will synthesize contemporary evidence surrounding CSF clearance at the nose-brain interface, examining across species this anatomical pathway, and its possible significance to human neurodegenerative disease. Our discussion of a bidirectional nasal pathway includes examination of the immune surveillance in the olfactory region protecting the brain. Overall, we expect that an expanded discussion of the brain-nose pathway and interactions with the environment will contribute to an improved understanding of neurodegenerative and infectious diseases, and potentially to novel prevention and treatment considerations.

Analytical profiling of Lentinan in hybrid nanostructures for intranasal Delivery: Method development and Validation

Lentinan (LNT) a polysaccharide obtained from mushroom Lentinus edodes, possesses potent anticancer and antitumor activity. To improve the bioavailability, encapsulation of LNT in polymer -lipid hybrid nanostructures (PLHNs) is done and administration via nasal pathway will bypass hepatic first-pass metabolism, which possibly will give high prospect for treatment of brain tumors. The estimation of entrapped LNT within Hybrid Nanostructures is one of the important parameters for the characterization of nanoparticles. Therefore, an analytical method was developed and validated for estimating plain LNT and LNT-PLHNs in Nasal Simulated Fluid (NSF) by conjugating with Congo Red (CR) in dilute alkaline solutions by employing high-performance liquid chromatography (HPLC). The developed method was validated for selectivity, linearity, precision, accuracy, robustness. The linearity was checked over the concertation range of 2–10 μg/mL the and limit of detection (LOD) and limit of quantification (LOQ) were 38.02 ± 0.21 ng/mL and 86.71 ± 0.82 ng/mL respectively. The mean percent recovery of LNT was 99.18 %; relative standard deviation (RSD) of 0.386 % and intra- and interday coefficient of variation was <2 %. The developed HPLC method was found suitable for assessing percent entrapment efficiency (%EE), in-vitro drug release, intracellular uptake study and stability profile of LNT-PLHNs obtained by solvent injection technique.

QS1: Nasopharyngeal Airway and Subcranial Space Analysis in Pfeiffer Syndrome

Background:Tracheotomy in infancy helps patients with Pfeiffer syndrome survive by preventing respiratory crisis, however, difficulty in decannulation consequently may be a challenge. This study attempts to investigate the regional abnormalities of the nasopharyngeal airway in Pfeiffer syndrome, to provide an anatomic basis for the upper airway surgical treatment and decannulation.Method:Seventy-two preoperative CT scans (Pfeiffer syndrome, n=30; control, n=42) were included in this study. The airway volume, cross-sectional area, and cephalometrics, were measured using Materialise software.Results:Patients with Pfeiffer syndrome developed a 50% (p<0.001) reduction of nasal airway volume, and a 44% (p=0.003) restriction in pharyngeal airway volume. The cross-sectional area of Pfeiffer patients at the choana, was only half that of normals’ (p<0.001). The posterior width of nasal airway in Pfeiffer syndrome was shortened by 13% (p=0.003), and the height was reduced by 21% (p<0.001). The cross-sectional areas at condylion and gonion levels, indicating the caliber of pharyngeal airway at entrance and midsection, were reduced by 67% (p<0.001) and 47% (p<0.001), respectively, when compared with normals.Conclusion:Nasal airway volume in Pfeiffer syndrome is significantly restricted, in length, height and width, along with the choanal stenosis in all cases in this cohort. The reduced anteroposterior length of nasal airway contributes to the shortened maxilla, more than the anteroposterior position. The limited nasal pathway height and width results from the hypoplastic sphenoid. Mediolateral and anteroposterior restricted dimensions are evident across the entire course of pharyngeal airway. Therefore, mediolateral maxillary expansion likely benefits Pfeiffer syndrome patients, in addition to maxillomandibular advancement.

Partial Maxillectomy for the Improvement of Nasal Obstruction Can Be Combined with Septorhinoplasty.

We describe the (anteromedial) partial maxillectomy technique which can be used to address impaired nasal breathing in cases of significant protrusion of the frontal process of the maxilla into the nasal cavity, narrowing the nasal pathway. It fits to nasal physiology avoiding mucosal resection. It can be combined with surgery of the inferior turbinate. The described technique can be used in all forms of rhinoplasty.

The liquid crystalline phase behaviour of a nasal formulation modifies the brain disposition of donepezil in rats in the treatment of Alzheimer's disease

Although nanoparticles, polymeric micelles, liposomes, nanoemulsions, and microemulsions were extensively evaluated as formulations for nasal administration of drugs, lyotropic liquid crystal (LLC) mesophases have been few studied. The phase transition from a low-viscosity microemulsion to a more viscous LLC may improve the mucoadhesion of the formulation. Donepezil is a drug administered orally in the treatment of Alzheimer’s disease, and with gastrointestinal side effects that are typical of acetylcholinesterase inhibitors. Based on this, donepezil administration by nasal pathway using a mucoadhesive LLC may be a feasible alternative. A colloidal formulation was selected from a ternary diagram, combining CETETH-10, oleic acid, and water (40:45:15, w/w). Donepezil was incorporated into the formulation, and the characterisation included in vitro studies, such as mucoadhesion and drug release. Pharmacokinetics in Wistar rats included evaluations by the nasal pathway with donepezil incorporated into microemulsion. A phase transition from an isotropic to an anisotropic system was observed after the swelling of the microemulsion with artificial nasal fluid (12–20 %). The release of donepezil in vitro occurred in a sustained manner. Significant levels of donepezil were achieved in the brain after nasal administration of the microemulsion, as a promising strategy for the treatment of Alzheimer’s disease.

Le Fort I osteotomy facilitated nasotracheal intubation in a patient with concha bullosa and septal deviation: a case report

Introduction: Nasotracheal intubation (NTI) is preferred for general anesthesia in maxillofacial surgery. However, NTI is often traumatic or even unsuccessful, particularly in patients with a narrow nasal pathway. In this case report, we describe a less traumatic NTI approach using maxillary downfracture of Le Fort I osteotomy. Case presentation: A 19-year-old woman was admitted with a skeletal Class III malocclusion and scheduled to undergo bimaxillary orthognathic surgery. A preoperative evaluation revealed no other medical history and abnormal laboratory findings. Preoperative computed tomography showed nasal septal deviation, concha bullosa, and turbinate hypertrophy. A nasal Ring-Adair-Elwyn endotracheal tube and a tube exchanger could not be inserted via NTI because of her narrow nasal cavity. An oral intubation was performed temporarily and surgery was started. After a maxillary downfracture was performed, which made the nasal cavity wider than before, NTI was successfully conducted without difficulty. The patient was ventilated without any problems, and the operation was continued. Postoperatively, the patient had no further complications and her vital parameters were all stable. Conclusions: This case report suggests that NTI after maxillary downfracture of Le Fort I osteotomy can be a good alternative that can be successfully performed with less trauma in patients undergoing orthognathic surgery who are preoperatively evaluated as having a narrow nasal cavity.

Nasopharyngeal airway and subcranial space analysis in Pfeiffer syndrome

Tracheotomy in infancy helps patients with Pfeiffer syndrome to survive by preventing respiratory crisis, but difficulty in decannulation may consequently be a challenge. This study has investigated the regional abnormalities of the nasopharyngeal airway in children with Pfeiffer syndrome to provide an anatomical basis for the surgical treatment and decannulation of the upper airway. Seventy-two preoperative computed tomograms (CT) (Pfeiffer syndrome n=30; control n=42) were included. The airway volume, cross-sectional area, and cephalometrics were measured using Materialise software. Patients with Pfeiffer syndrome developed a 50% (p<0.001) reduction of nasal airway volume, and a 44% (p=0.003) restriction in pharyngeal airway volume. In patients with Pfeiffer syndrome the cross-sectional area at the choana was only half that of the controls (p<0.001). The posterior width of the nasal airway in patients with Pfeiffer syndrome was shortened by 13% (p=0.003), and the height reduced by 21% (p<0.001). The cross-sectional areas at the condylion and gonion levels, which indicate the calibre of the pharyngeal airway at the entrance and midsection, were reduced by 67% (p<0.001) and 47% (p<0.001), respectively, when compared with the controls. The volume of the nasal airway in patients with Pfeiffer syndrome was significantly restricted in length, height, and width, and by choanal stenosis in all cases in this cohort. The reduced anteroposterior length of the nasal airway contributed to the shortened maxilla more than the anteroposterior position. The limited height and width of the nasal pathway was the result of a hypoplastic sphenoid. Restricted mediolateral and anteroposterior dimensions were evident across the entire course of the pharyngeal airway. Mediolateral maxillary expansion in addition to maxillomandibular advancement is therefore likely to benefit these patients.

Effect of bevel direction on the tracheal tube pathway during nasotracheal intubation: A randomised trial.

For nasotracheal intubation, the nasal pathway between the inferior turbinate and hard palate (lower pathway) is preferred for patient safety. However, selecting the lower pathway can be challenging because passage of the tube through the nasal pathway is usually performed blindly. We investigated whether facing the bevel of the tracheal tube in the cephalad direction of the patient could help in advancing the tracheal tube through the lower pathway during nasotracheal intubation. A randomised, blinded trial. SMG-SNU Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea from January 2019 to March 2020. Sixty-eight adult patients undergoing oromaxillary surgeries were enrolled in this study. Patients were randomly allocated to undergo nasotracheal intubation with the bevel of the tube facing the cephalad direction (intervention group) or to the left (conventional group). The effects of bevel direction on the pathway of the tube in the nasal cavity, and the incidence of epistaxis were evaluated by fibreoptic bronchoscopy. The success rate of the tracheal tube passing through the lower pathway was significantly higher in the intervention group than the conventional group (79.4 vs. 55.9%, relative risk 1.421, 95% CI 1.007 to 2.005, P = 0.038). The incidence of epistaxis was also lower in the intervention group than in the conventional group (41.2 vs. 73.5%, relative risk 0.560, 95% CI 0.357 to 0.878, P = 0.007). Facing the bevel of the tracheal tube in the cephalad direction of the patient facilitated selection of the lower pathway and reduced the incidence of epistaxis during nasotracheal intubation in patients undergoing oromaxillary surgery. ClinicalTrial.gov, NCT03740620.

Synthesis and characterization of thermosensitive hydrogel based on quaternized chitosan for intranasal delivery of insulin.

Nasal administration is a form of systemic administration in which drugs are insufflated through the nasal cavity. Steroids, nicotine replacement, antimigraine drugs, and peptide drugs are examples of the available systematically active drugs as nasal sprays. For diabetic patients who need to use insulin daily, the nasal pathway can be used as an alternative to subcutaneous injection. In this regard, intranasal insulin delivery as a user-friendly and systemic administration has recently attracted more attention. In this study, a novel formulation consists of chitosan, chitosan quaternary ammonium salt (HTCC), and gelatin (Gel) was proposed and examined as a feasible carrier for intranasal insulin administration. First, the optimization of the chitosan-HTCC hydrogel combination has done. Afterward, Gel with various amounts blended with the chitosan-HTCC optimized samples. In the next step, swelling rate, gelation time, degradation, adhesion, and other mechanical, chemical, and biological properties of the hydrogels were studied. Finally, insulin in clinical formulation and dosage was blended with optimized thermosensitive hydrogel and the release procedure of insulin was studied with electrochemiluminescence technique. The optimal formulation (consisted of 2wt% chitosan, 1wt% HTCC, and 0.5wt% Gel) showed low gelation time, uniform pore structure, and the desirable swelling rate, which were resulted in the adequate encapsulation and prolonged release of insulin in 24H. The optimal samples released 65% of the total amount of insulin in the first 24H, which is favorable for this study.