Nasal Solution Research Articles

The effect of topical medications on olfactory function: Barrier therapy

Introduction. Sensory organs help humans exist in the surrounding world, but the evaluation of olfaction remained “in the shadows” practically until the COVID-19 pandemic, although many questions are still insufficiently studied, such as the effect of intranasal medications on olfactory function.Aim. To assess the olfactory function in healthy volunteers before and after a course of using an ectoine nasal solution.Materials and methods. Under our observation were healthy volunteers (medical university students and healthcare workers aged 16 to 35 years) who, in addition to routine ENT examinations, underwent an assessment of their olfactory status using a professional set of odorants for olfactometry and subjectively using a self-assessment scale for olfaction before and after a course of ectoine nasal solution, as well as a self-assessment of its preventive effect. The collected data were recorded in Excel spreadsheets (Microsoft Office 365) for further statistical analysis.Results and discussion. The results showed an average increase of 1 point in the self-assessment of olfaction in the observation group, as well as an increase in the number of “correct” responses when using the set of odorants. However, discrepancies were noted between self-assessment and the objective evaluation of olfaction. The extent of the preventive effect (based on the self-assessment by participants using a 10-point visual analog scale) was rated at 5 points.Conclusions. 1. A one-month course of barrier therapy (ectoine nasal solution) does not cause any impairment in olfactory function, as evidenced by olfactometric testing (an average increase of 10% in correct responses across the group, with 80% of participants showing improvement) and olfaction self-assessment (an average increase of 1 point across the group, with 55% of participants showing improvement). 2. Self-assessment of olfaction cannot be considered a reliable measure of the actual olfactory function. 3. The use of barrier therapy (ectoine nasal solution) has a moderate preventive effect (5 points).

Resveratrol plus carboxymethyl-β-glucan for children with respiratory diseases.

Respiratory infections in children, ranging from mild to severe, are a leading cause of school absences and medical visits, creating significant socio-economic burdens for families. Recent interest has focused on resveratrol, a natural polyphenol known for its antioxidant, anti-inflammatory, and antiviral properties. When combined with carboxymethyl-β-glucan (CM-glucan), a modified polysaccharide with immunostimulatory effects, this formulation has shown potential benefits in managing respiratory diseases.Our research examines five randomized clinical trials investigating the efficacy of resveratrol and CM-glucan nasal solutions in children. The trials included children with recurrent respiratory infections (RRIs) and allergic rhinitis. The results demonstrate significant reductions in key respiratory symptoms, including nasal congestion, sneezing, coughing, and fever. In addition to symptomatic relief, the treatment was associated with fewer medical visits, decreased medication use, and reduced school absences. Importantly, the combination also showed efficacy in decreasing wheezing episodes in non-atopic children with RRIs and improving symptoms of allergic rhinitis. While these findings are promising, the studies are limited by small sample sizes and short-term follow-up periods, raising questions about the long-term efficacy and safety of the treatment. Mild and transient nasal irritation was the only reported side effect. Based on these concepts, the combination of resveratrol and carboxymethyl-β-glucan could be considered a valuable add-on strategy, complementing standard pharmacological treatments for pediatric respiratory infections and allergic conditions.

Microplastics in different nasal irrigation options.

We aimed to assess the presence of microplastics in nasal irrigation methods commonly used in the treatment of sinusitis and rhinitis, and to evaluate human exposure. A total of 150 samples were included in the study, consisting of nasal wash bottles containing nasal irrigation solution, seawater spray, syringes for nasal irrigation with isotonic solution. The amount of microplastics per millilitre in the samples and patient exposure during single use were assessed separately for each method and product. All samples were filtered using a stainless steel vacuum filter on filter paper with a pore size of 1.2μm, washed at least three times with distilled water and incubated at 45°C for 24h to prevent mould growth. Identification and counting of microplastics was performed using a Leica Flexacam C1 camera connected to an M80 stereomicroscope. The presence of microplastics was confirmed by the hot needle method and Nile red staining. An average of 6.49 ± 13.08 microplastics/product was detected in all filtered samples. The lowest microplastic count was 0 microplastics/product in syringes and the highest was 92 microplastics/product in nasal wash bottles. Significant differences in the amount of microplastics individuals were exposed to during a single use were found between nasal wash bottles and seawater brands, while no significant differences were found between syringe brands. When nasal wash kits, seawater sprays and isotonic nasal rinses were evaluated separately, significant differences were found in the number of microplastics, the microplastics/ml ratio and the number of microplastics exposed during a single use. The highest microplastic exposure was found in nasal irrigation bottles. The exposure of individuals to microplastics increases with medical support treatments, regardless of intranasal or intravenous administration. Due to the inflammation, oxidative stress and proliferation caused by microplastics, new regulations and inspections of production conditions should be implemented worldwide to reduce exposure.

A thermosensitive chitosan hydrogel: An attempt for the nasal delivery of dimethyl fumarate

Dimethyl fumarate (DMF) is a drug that is orally administered for the treatment of relapsing-remitting multiple sclerosis. However, DMF causes gastrointestinal side effects and flushing in 43 % of patients, which significantly contributes to treatment discontinuation. To reduce side effects and increase patient compliance, the aim of this study was to develop a thermosensitive chitosan/glycerophosphate hydrogel for the nasal administration of DMF. A binary system of DMF with hydroxypropyl-β-cyclodextrin (HP-β-CD) was made and included in the hydrogel precursor solution. The precursor solution (drug content, DMF stability, thermogelling properties, viscosity), and the resulting thermosensitive hydrogel (mucoadhesion, in vitro DMF permeation) were characterized. HP-β-CD was able to interact with DMF and improve its water solubility. The leader thermosensitive nasal solution, G1 solution, was loaded with approximately 92 % DMF, which remained stable for 21 days. The G1 solution formed a hydrogel in approximately 2–1 min; it had a pH of 6.8 ± 0.06 and caused no significant change in the osmolality of the simulated nasal medium. The G1 hydrogel showed good mucoadhesive properties and released DMF that permeated in vitro in a controlled manner. As a result, G1 is a potential new approach to exploit the intranasal administration of DMF for treating multiple sclerosis.

Nasal microbiome and the effect of nasal decolonization with a novel povidone-iodine antiseptic solution: a prospective and randomized clinical trial

The aim of this study was to assess the profile of nasal microbiome and evaluate the effect of a specific nasal decolonization solution on the microbiome. We conducted a randomized, placebo-controlled, and parallel-group clinical study of 50 volunteers aged 18 years and older. The subjects were randomly assigned to receive a nasal antiseptic solution, containing povidone-iodine as the main ingredient, (n = 25) or a control solution (n = 25). Nasal swabs were obtained before application (baseline) and at 3 timepoints after application (5 min, 2 h, 24 h). Nasal swabs were subjected to next generation sequencing analysis and cultured in agar plates. At baseline, there were substantial associations between anaerobic species, Corynebacterium spp., Staphylococcus spp., and Dolosigranulum spp. Then, a high bioburden reduction was observed after the application of povidone-iodine (log10 3.68 ± 0.69 at 5 min; log10 3.57 ± 0.94 at 2 h; log10 1.17 ± 1.40 at 24 h), compared to the control. The top species affected by the treatment were Cutibacterium acnes, Staphylococcus, and Corynebacterium species. None of the subjects experienced any adverse effects, nor increases in mucociliary clearance time. Antiseptic solutions applied to the anterior nares can transiently and markedly reduce the bioburden of the nose. The registration number for this clinical trial is NCT05617729.

Effects of Nasal Solution Incorporating Resveratrol and Carboxymethyl-Β-Glucan in Preschool Non-Atopic Children with Wheezing.

Upper respiratory tract infections (URTI) account for more than 80% of wheezing episodes in children with a high incidence of hospitalization in preschool age. Most children with symptoms of wheezing during an URTI are usually non-atopic. As the majority of wheezing episodes resulting from URTI are attributed to viral triggers, several studies have suggested the potential anti-inflammatory and antiviral properties of resveratrol. This study aims to identify the effect of resveratrol for pediatric non-atopic patients with recurrent wheezing triggered by URTIs. We conducted a prospective single-blind study to assess the effectiveness of a short course of nasal solutions incorporating resveratrol and carboxymethyl-β-glucan, administered for 7 days at the onset of URTIs, compared to standard nasal lavage with 0.9% saline solution. A total of 19 patients entered the active group, 20 patients were assigned to the placebo group. The comparison of overall wheezing days (p < 0.001), mean wheezing days per month (p < 0.01), and wheezing episodes per patient (p < 0.001) in the two groups showed a significant reduction in the group receiving resveratrol compared with the placebo group, with less hospital access (p < 0.001) and oral corticosteroid administration (p < 0.01). Our findings seem to suggest that, in non-atopic children with recurrent wheezing secondary to URTIs, nasal resveratrol could be effective to prevent or reduce the occurrence of wheezing, when started from the onset of upper airway symptoms.

Development of thermosensitive liposome-containing in-situ gel systems for intranasal administration of thiocolchicoside and in vivo evaluation in a rabbit model

Aim Thiocolchicoside (THC) is a drug under the category of BCS III. Due to its high molecular weight, it has poor oral bioavailability and low skin permeability. This study aims to find an alternative delivery method for THC that enhances its bioavailability through nasal application approach. In situ gels containing plain or liposomal THC with different combinations of Pluronic® F127 and PEG 400 were prepared. Method Liposome formulations were prepared using the thin film hydration method and tested for their characterization such as for drug content, particle size, and zeta potential. In vivo pharmacokinetic parameters of formulations such as Cmax, Tmax, and AUC were tested on the rabbit model. The formulations were also scrutinized for their cell viability properties. Result Formulation composition with 2% soybean phosphatidylcholine and 10 mg THC exhibited ∼94% entrapment efficiency, minimum particle size 101.32 nm, low polydispersity index 0.225 and +0.355 zeta potential. In situ liposomal dispersion containing 15% Pluronic® F127 turned into gel at nasal temperature. Cell lines were unharmed for 48 h. İn situ liposomal gels showed 1.5x higher blood concentration than the control formula. Conclusion In situ gels of liposomal THC formulations offer advantages over traditional nasal solutions, demonstrating comparable bioavailability to parenteral medication while also preserving the health of nasal mucosa cells.

Immobilization of human tyrosine hydroxylase onto magnetic nanoparticles – A novel formulation of a therapeutic enzyme

Human tyrosine hydroxylase (hTH) has key role in the production of catecholamine neurotransmitters. The structure, function and regulation of hTH has been extensively researched area and the possibility of enzyme replacement therapy (ERT) involving hTH through nanocarriers has been raised as well. However, our understanding on how hTH may interact with nanocarriers is still lacking. In this work, we attempted to investigate the immobilization of hTH on magnetic nanoparticles (MNPs) with various surface linkers in quantitative and mechanistic detail. Our results showed that the activity of hTH was retained after immobilization via secondary and covalent interactions as well. The colloidal stability of hTH could be also enhanced proved by Dynamic light scattering and Zeta potential analysis and a homogenous enzyme layer could be achieved, which was investigated by Raman mapping. The covalent attachment of hTH on MNPs via aldehyde or epoxy linkers provide irreversible immobilization and 38.1 % and 16.5 % recovery (ER). The hTH-MNPs catalyst had 25 % ER in average in simulated nasal electrolyte solution (SNES). This outcome highlights the relevance of immobilization applying MNPs as a potential formulation tool of sensitive therapeutic enzymes offering new opportunities for ERT related to neurodegenerative disorders.

(005) Can Novel SDS-089 Nasal Vardenafil Spray Solution Achieve Satisfactory Drug Plasma Level Similar to Oral Vardenafil Formulation? A Bioanalysis Study Comparing Vardenafil Nasal vs Oral Formulations Using Liquid Chromatography Tandem Mass Spectrometry

Abstract Introduction The nasal drug delivery system offers many advantages when compared with oral administration, such as a faster onset of action, easily accessible, less drug degradation, and a high rate of absorption. The SDS-089 nasal Vardenafil (VDF) solution is a unique drug formulation designed to be delivered as a spray formulation. Objective To assess the bioavailability of SDS-089 nasal Vardenafil solution in human plasma levels using Liquid Chromatography Tandem Mass Spectrometry analysis. Methods The SDS-089 Vardenafil HCl formulation was prepared with the active pharmaceutical ingredient to the United States Pharmacopeia (USP) standard (batch 1704002361). The SDS-089 nasal spray solution was filtered (0.22 μm filter) and fitted with a nasal spray device to deliver 100 μL per spray which is equivalent to 2 mg Vardenafil HCl alcoholic solution per spray. This study received approval from the Institutional Review Board and Biosafety Committee (FB18/IRB/099). Blood samples from participants were collected at time 0 (pre-dose) and across different time intervals up to 10 hours and analyzed using Liquid Chromatography Tandem Mass Spectrometry (LC/MS) to quantify the level of Vardenafil and the internal standard. This protocol allows for the preparation and analysis of human samples, quality controls (QC), standard curve preparation, and instrumental analysis. During the validation experiments, each calibration standard and QC sample was prepared by spiking a specified amount of Vardenafil in human plasma with oral Vardenafil drug served as the internal standard for comparison. The concentration of analytes in each standard was quantified using LC/MS and detected using multiple-reaction monitoring for each of the respective analytes. The lower limit of quantitation (LLOQ) was defined as the lowest concentration that could be quantified with accuracy and precision within 20%, as calculated from chromatograms for the independent samples. Intra- and inter-run accuracy and precision were calculated for the three QC samples, and independent triplicate measurements with best-fit lines were selected using a linear regression model with a 1/x2 weighting factor in the calibration curves. Results The SDS-089 nasal Vardenafil solution showed excellent accuracy (mean 100, Standard Deviation, SD 4.1, % Relative Standard Deviation, RSD of 4%) and good precision (mean 50.1, SD 2.1, %RSD of 4%) on high (50ng/ml) QC assay tests. Similarly, the stability of QC on high (50ng/ml) plasma assay tests showed excellent accuracy (mean 100.8, SD 3.7, %RSD of 4%) and good precision (mean 50.4, SD 1.8, %RSD of 4%) on high (50ng/ml). Comparison between pharmacokinetic parameters of Vardenafil SDS-089 nasal spray (4mg) and oral tablet (10mg) showed T1/2 (2.52±0.99 vs 2.46±0.73 hour), Tmax (0.17±0.54 vs 0.97±0.35 hour), Cmax (time concentrations) (9.21±4.11 vs 11.24±7.83 ng/mL) and AUC0-inf (area under the curve from zero to infinity) (21.03±12.54 vs 37.25±41.51 ng/mL*h) (see Table 1: Pharmacokinetic parameters of Vardenafil HCI as SDS-089 nasal spray vs. oral tablet using non-compartmental analysis WinNonlin software). Conclusions SDS-089 nasal formulation appeared to deliver a high plasma concentration level of Vardenafil drug based on pharmacokinetic LC/MS data analysis with robust accuracy and precision. Disclosure Yes, this is sponsored by industry/sponsor: LTR Pharma Clarification: Industry funding only - investigator initiated and executed study

The Use of Ipratropium Bromide for the Treatment of Pediatric Sialorrhea: A Retrospective Clinical Case Series.

This retrospective review documents the experience of ipratropium bromide use among pediatric patients with sialorrhea at our multidisciplinary sialorrhea clinic at Children's Hospital at London Health Sciences Centre (LHSC). A retrospective chart review of patients diagnosed with sialorrhea at our multidisciplinary clinic between January 2015 and June 2021 was completed. Data on patient demographics, comorbidities, clinical presentation, previous interventions, quality of life, and medication adverse side effects was collected. Drooling Frequency and Severity Scale (DFSS) scores were reviewed to compare sialorrhea management pre- and post-treatment with topical 0.03% ipratropium bromide nasal solution. A descriptive analysis and Wilcoxon signed rank tests were conducted to compare pre- versus post-treatment DFSS scores. A total of 12 patients presented for follow-up and were included in the final analysis. At the pre-treatment visit, the median DFSS score was 4 for frequency and 5 for severity. Post-treatment, median DFSS score was 3 for frequency and 4.5 for severity, (P = .020 and .129, respectively). Minimal adverse effects were encountered. Ipratropium bromide provided a statistically significant benefit for drooling frequency in the patients studied and may present an additional topical medical option for pediatric sialorrhea with limited adverse effects.

266. Nasal Microbiome and the Effect of Nasal Decolonization with a Novel PovidoneIodine Antiseptic Solution: A Prospective and Randomized Clinical Trial

Abstract Background The presence of pathogenic bacteria in the anterior nares has gained substantial attention due to its association with an increased risk for surgical site infections. Nasal decolonization has been shown to reduce the risk for SSIs. Recent studies have suggested that the profile of the nose microbiome is a determining factor for the susceptibility to develop SSIs. Therefore, this prospective clinical trial was set up to study the profile of nasal microbiome and test the effect of a specific nasal decolonization solution on the microbiome. Methods We conducted a prospective study on 50 individuals who were randomly assigned to receive a nasal antiseptic solution (n=25) or a control PBS solution (n=25). The antiseptic solution (containing povidone-iodine [PVP-I] as the main ingredient) or PBS was administered with a cotton swab and a rotatory movement for 15 s in the anterior part of both nares. Nasal swabs were obtained before application (baseline) and at 3 different timepoints after application (5 min, 2 h, and 24 h). Nasal swabs were subjected next generation sequencing (NGS) analyses and cultured in trypticase soy agar plates. Study design Fifty volunteers were recruited for this randomized clinical trial. Block randomization was performed to determine group allocation, thus, PVP-I (n=25) or PBS (n=25) application in the anterior nares. We assessed bioburden at baseline, 5 minutes, 2 hours, and 24 hours post-application, meanwhile microbial diversity and mucociliary clearance was assessed at baseline and 24 hours post-application. Bacterial associations were assessed at baseline and non-desired events were examined at every follow-up visit. Results A high bioburden reduction was observed after the application of PVP-I (log10 3.538 ± 0.918 at 5 min; log10 2.961 ± 1.466 at 2 hours; and log10 0.849 ± 1.092 at 24 hours; p&amp;lt; 0.01), compared to PBS. At baseline, there were substantial associations between anaerobic species, Corynebacterium spp, Staphylococcus spp, and Dolosigranulum spp. The top species affected by the treatment were C. acnes, Staphylococcus, and Corynebacterium species, among others. None of the subjects in the study experienced any adverse effects associated with this study, nor increases in MCC time. Bioburden reduction (A) and mucociliary clearance assessment (B) A) Data is expressed as mean ± SEM CFU log10 reduction, from baseline bioburden. B) Sweetness detection, in minutes, at baseline and 24 hours post-application. Bacterial composition. A) Relative abundance of the most prevalent bacterial species and B) heatmap illustrating the mean relative abundance of bacteria detected to be differentially abundant by ANCOMBC procedure. A cell colored in black can be considered “true” zero, whereas there were no detections of a particular bacteria for that given cell. Network plot shows associations among bacterial species with p&amp;lt;0.10. Each node represents a species and is linked by species associations. Conclusion There was a considerable difference in the profile of nasal microbiome organisms between individuals. Intranasal application of the PVP-I antiseptic led to a substantial reduction of the nasal flora for up to 24 hours after application. Restoration of the microbial population was observed with slight variations to the baseline profiles. Antiseptic solutions applied to the anterior nares can transiently and markedly reduce the bioburden of the nose. Disclosures Javad Parvizi, MD, FRCS, 3M: Grant/Research Support|Acumed, LLC: Stocks/Bonds|Aesculap: Grant/Research Support|Alphaeon: Stocks/Bonds|AO Spine: Stocks/Bonds|Becton Dickenson: Advisor/Consultant|Biomet: Grant/Research Support|Cardinal Health: Advisor/Consultant|Cempra: Grant/Research Support|CeramTec: Grant/Research Support|Ceribell: Stocks/Bonds|Coracoid: Stocks/Bonds|Corentec: Advisor/Consultant|Datatrace: Grant/Research Support|DePuy: Grant/Research Support|Elsevier: Grant/Research Support|Elute: Stocks/Bonds|Ethicon: Advisor/Consultant|Hip Innovation Technology: Stocks/Bonds|Illuminus: Stocks/Bonds|Integra: Grant/Research Support|Intellijoint: Stocks/Bonds|Jaypee Publishers: Grant/Research Support|KCI / 3M (Acelity): Advisor/Consultant|Lima: Grant/Research Support|MicroGenDx: Advisor/Consultant|Molecular Surface Technologies: Stocks/Bonds|Myoscience: Grant/Research Support|Nanooxygenic: Stocks/Bonds|National Institutes of Health (NIAMS &amp; NICHD): Grant/Research Support|NDRI: Grant/Research Support|Novartis: Grant/Research Support|OREF: Grant/Research Support|Orthospace: Grant/Research Support|Osteal: Stocks/Bonds|Parvizi Surgical Innovations and Subsidiaries: Stocks/Bonds|Peptilogic: Stocks/Bonds|Peptilogics: Advisor/Consultant|Pfizer: Grant/Research Support|PRN-Veterinary: Grant/Research Support|Rotation Medical: Grant/Research Support|Simplify Medical: Grant/Research Support|SLACK Incorporated: Grant/Research Support|Smith &amp; Nephew: Grant/Research Support|Sonata: Stocks/Bonds|Stelkast: Grant/Research Support|Stryker: Grant/Research Support|Synthes: Grant/Research Support|Tenor: Advisor/Consultant|TissueGene: Grant/Research Support|Tornier: Grant/Research Support|Wolters Kluwer Health - Lippincott Williams &amp; Wilkins: Grant/Research Support|Zimmer Biomet: Advisor/Consultant|Zimmer Biomet: Grant/Research Support

Preparation and Optimization of Bovine Serum Albumin Nanoparticles as a Promising Gelling System for Enhanced Nasal Drug Administration.

Bovine serum albumin (BSA) has been used extensively as a suitable carrier system for alternative drug delivery routes, such as nasal administration. However, the optimization of BSA nanoparticles with respect to their nasal applicability has not been widely studied. The present study focuses on the characterization of BSA nanoparticles prepared using the desolvation method, followed by a gelation process to facilitate intranasal drug delivery. The results demonstrated that the ratio of BSA and the desolvating agent, ethanol, played a critical role in the nanoparticle characteristics of the BSA nanogel matrices (BSA-NGs). Based on the gelling properties, the formulations of BSA-NG 2, BSA-NG 4, and BSA-NG 6 were selected for further investigation. The Raman spectra confirmed that there were no specific changes to the secondary structures of the BSA. The mucoadhesion studies revealed moderately high mucoadhesive properties, with a mucin binding efficiency (MBE) value of around 67%, allowing the dose to avoid elimination due to rapid mucociliary clearance of the nasal passage. Via studying the nexus of the carrier system, BSA-NGs loaded with dexamethasone as a model drug were prepared and evaluated by differential scanning calorimetry (DSC) and thermal gravimetry (TG), ascertaining that no ethanol remained in the samples after the freeze-drying process. Furthermore, the viscosity measurements exhibited moderate viscosity, which is suitable for nasal liquid preparations. The in vitro release studies performed with a simulated nasal electrolyte solution (SNES) medium showed 88.15-95.47% drug release within 4 h. In conclusion, BSA nanoparticle gelling matrices can offer potential, value-added drug delivery carriers for improved nasal drug administration.

Synthesis and characterization of magnetic molecularly imprinted polymer of polydopamine/graphene oxide as drug carrier for rivastigmine

In this study, a magnetic molecularly imprinted polymer based on magnetic graphene oxide and polydopamine (PDA) was synthesized, and its application in a drug delivery system (DDS) for rivastigmine (RIV) was investigated. In order to investigate the effect of imprinting on the performance of the MIP-GO/Fe3O4/PDA, its non-imprinted polymer (NIP-GO/Fe3O4/PDA) was also synthesized. Various analyses such as Fourier transform infrared spectrometer (FT-IR), scanning electron microscopy (SEM), thermal gravimetric analysis (TGA), vibrating-sample magnetometer (VSM), N2 adsorption and desorption (Brunauer-Emmett-Teller, BET), energy dispersive X-ray analysis (EDX), and X-ray diffraction analysis (XRD) were used to characterize the prepared polymers. The isotherm and kinetics studies for the drug loading process were done and modeled by various models. Drug release was performed in buffers with different pHs of 2.2, 6.4, 7.4, and 9, and in addition, in simulated nasal electrolyte solution (SNES) buffer. In addition, to investigate the drug release mechanisms, different models were studied. The results of this study showed that the drug loading process in this polymer follows the Freundlich isotherm model and the pseud-second-order model. The maximum efficiency of drug loading on the MIP and NIP was 96.44% and 72.78% at 400 ppm drug concentration, respectively. The results of drug release by these two polymers showed that molecularly imprinted techniques caused controlled drug release carriers, and the maximum amount of drug released from this polymer was 78.65% (301.98 ppm) at pH 9. In addition, the results of drug release modeling showed that the mechanism of rivastigmine release from MIP-GO/Fe3O4/PDA is Fickian diffusion.

Assessment of safety and intranasal neutralizing antibodies of HPMC-based human anti-SARS-CoV-2 IgG1 nasal spray in healthy volunteers

An HPMC-based nasal spray solution containing human IgG1 antibodies against SARS-CoV-2 (nasal antibody spray or NAS) was developed to strengthen COVID-19 management. NAS exhibited potent broadly neutralizing activities against SARS-CoV-2 with PVNT50 values ranging from 0.0035 to 3.1997 μg/ml for the following variants of concern (ranked from lowest to highest): Alpha, Beta, Gamma, ancestral, Delta, Omicron BA.1, BA.2, BA.4/5, and BA.2.75. Biocompatibility assessment showed no potential biological risks. Intranasal NAS administration in rats showed no circulatory presence of human IgG1 anti-SARS-CoV-2 antibodies within 120 h. A double-blind, randomized, placebo-controlled trial (NCT05358873) was conducted on 36 healthy volunteers who received either NAS or a normal saline nasal spray. Safety of the thrice-daily intranasal administration for 7 days was assessed using nasal sinuscopy, adverse event recording, and self-reporting questionnaires. NAS was well tolerated, with no significant adverse effects during the 14 days of the study. The SARS-CoV-2 neutralizing antibodies were detected based on the signal inhibition percent (SIP) in nasal fluids pre- and post-administration using a SARS-CoV-2 surrogate virus neutralization test. SIP values in nasal fluids collected immediately or 6 h after NAS application were significantly increased from baseline for all three variants tested, including ancestral, Delta, and Omicron BA.2. In conclusion, NAS was safe for intranasal use in humans to increase neutralizing antibodies in nasal fluids that lasted at least 6 h.

Nasal lavage technique reveals regular inhalation exposure of microplastics, not associated from face mask use

During the COVID-19 pandemic, the use of face masks has been a worldwide primary protection measure to contain the spread of the virus. However, very little information is known about the possible inhalation of microplastics (MP) from wearing masks. This pilot study evaluates the presence of MP accumulated in nasal cavities through the nasal lavages technique. Six different commercial face masks were tested in 18 participants during five working days (8 h use/day). Eight different polymers (polystyrene, polyamide, poly(ethylene – propylene) diene monomer, polyester, polyethylene, polyvinylidene fluoride, polypropylene, and polyvinyl chloride) predominantly within the 20–300 µm size were detected in nasal lavages, with an average concentration of 28.3 ± 15.6 MP/5 mL nasal solution. Results demonstrate that MP in the nasal cavity are not associated to face mask use but rather to general exposure to airborne MP. We highlight the use of nasal lavages to evaluate human inhalation of MP and associate it to potential sources and risks.

Topical Cocaine Hydrochloride Nasal Solution: Anesthetic and Surgical Considerations.

Adequate surgical view during various types of nasal procedures is essential for surgical operations to be performed in a safe, efficient, and successful manner. Minimizing bleeding during surgery is an important way of increasing visualization that is commonly achieved by using a vasoconstrictive agent to control intraoperative hemorrhage. Many otolaryngologists choose to employ topical cocaine to minimize bleeding during surgery owing to its vasoconstrictive properties, while simultaneously benefitting from its dual local anesthetic effects. The relative benefit of topical cocaine for otolaryngologic procedures when compared to other topical analgesics and vasoconstrictors remains a topic of discussion due to the multiple potential cardiac and central nervous system side effects associated with cocaine administration. Furthermore, there is not a scientifically backed maximal safe dose published; instead, most of the guidelines for intranasal cocaine use are based on untested clinical practice. Despite this, the short latency, adequate duration of action, and inherent vasoconstrictive and decongestive capabilities make cocaine a valuable anesthetic agent for use in clinical procedures. As the relative benefit of using topical cocaine compared to the use of other vasoconstrictors and analgesics for nasal procedures remains undetermined in the current literature, this leaves the need for a comprehensive review of research that explores the risks and benefits of using topical cocaine in nasal procedures based on clinical trials that compare intranasal cocaine with various other analgesics and vasoconstrictors.

IODINE AS A POTENTIAL FRONT-LINE DEFENSE AGAINST COVID-19: A LITERATURE REVIEW

The novel coronavirus disease, first identified in 2019 known as COVID-19, is caused by a new strain of severe acute respiratory syndrome coronavirus (SARS-CoV or SARS-CoV-1), named SARS-CoV-2. Recent studies showed that the virus may be airborne and spreads through small respiratory droplets of saliva in aerosols, indirect or direct physical contact with the affected individual, in a similar way to the cold and influenza. Emerging studies also demonstrate the importance of the throat along with salivary glands as sites of viral replication and transmission in early COVID-19 infection. The most common route of entry of SARS-CoV-2 is the upper respiratory tract (nasopharynx) that slowly reaches the lower respiratory tract to infect the epithelial cells within the lungs which can cause lung damage and severe respiratory symptoms, if not treated immediately. Averting colonization of the virus in the nasopharynx could be one of the best options to reduce the incidence of severe infection. It has been well-documented that iodine is one of the most effective of all antimicrobials available. Hospitals and medical facilities worldwide use povidone-iodine (PVP-I) as a standard of care in infection control. Several research studies during the ongoing COVID-19 pandemic showed the in vitro and in vivo efficacy of iodine-containing solutions such as PVP-I (Betadine), Iodine-V (Essential Iodine Drops) etc. and other iodine complexes to effectively kill the SARS-CoV-2 virus within few seconds to hours. Few commercially available iodine-containing gargling, mouthwash, and nasal spray solutions have been recommended to use in humans against SARS-CoV-2 infection by experts to prevent viral spread, especially among health workers. The present article aims to summarize these studies and highlights the rationale, safety and recommendations of use of iodine as an effective method to decrease the viral load during the early COVID-19 infection.

Effect of anionic and nonionic hydrotropes on the clouding behavior and thermodynamic properties of nonionic surfactant and ciprofloxacin hydrochloride drug mixture

In the present study, the cloudy development of nonionic triton X-100 (TX-100) and an antibiotic drug ciprofloxacin hydrochloride (CFH) mixture has been conducted by applying the cloud point (CP) measurements method. The CP of TX-100 + CFH mixture was examined in aqueous solutions of hydrotropes (HDTs) (sodium benzoate (NaBenz), sodium salicylate (NaSal), 4-amino benzoic (4-ABA), polyethylene glycol (PGE) and Caffeine (CAF)). The TX-100 and CFH concentration were conserved constant at 50 and 1 mmol kg−1 correspondingly throughout the investigation. The CP values of TX-100 + CFH solution were augmented in the existence of NaBenz, NaSal, CAF along with PEG but diminished in aq. 4-ABA solution; the effects were obtained to be augmented with the enhancing hydrotropes contents. The CP values for TX-100 + CFH mixture in aq. hydrotropes media follow the pattern: CP(aq.4-ABA)<CPaq.CAF≈CPaq.PEG<CPaq.NaBenz<CPaq.NaSal. Therefore, the solubility of TX-100 + CFH mixture is achieved to be decreased in aq. solutions of 4-ABA while the solubility experienced an enhancement in aq. NaSal, NaBenz, PEG and CAF solutions. Among hydrotropes used in the present study, NaSal is the most effective solubility enhancer. The free energy (ΔGc0) were achieved to be positive in all the solvent media used in the study which exposes that the cloudy development process isnot spontaneous. The enthalpy (ΔHc0) and the entropy (ΔSc0) of clouding were obtained to be positive in hydrotropes media. The ΔHc0 and ΔSc0 values imply that the main forces of the cloudy formation in TX-100 and CFH system are hydrophobic interaction, hydrogen bonding, and electrostatic interactions. The compensation temperature (Tc) along with the intrinsic enthalpy gain (ΔHc0,∗) were also calculated and discussed. It is probable that the knowledge gained from these types of studies will be quite helpful in both pharmaceutics formulations and drug delivery system.

Aqueous cannabidiol β-cyclodextrin complexed polymeric micelle nasal spray to attenuate in vitro and ex vivo SARS-CoV-2-induced cytokine storms

Cannabidiol (CBD) has a number of biological effects by acting on the cannabinoid receptors CB1 and CB2. CBD may be involved in anti-inflammatory processes via CB1 and CB2 receptors, resulting in a decrease of pro-inflammatory cytokines. However, CBD's poor aqueous solubility is a major issue in pharmaceutical applications. The aim of the present study was to develop and evaluate a CBD nasal spray solution. A water-soluble CBD was prepared by complexation with β-cyclodextrin (β-CD) at a stoichiometric ratio of 1:1 and forming polymeric micelles using poloxamer 407. The mixture was then lyophilized and characterized using FT-IR, DSC, and TGA. CBD-β-CD complex-polymeric micelles were formulated for nasal spray drug delivery. The physicochemical properties of the CBD-β-CD complex-polymeric micelle nasal spray solution (CBD-β-CDPM-NS) were assessed. The results showed that the CBD content in the CBD-β-CD complex polymeric micelle powder was 102.1 ± 0.5% labeled claim. The CBD-β-CDPM-NS was a clear colorless isotonic solution. The particle size, zeta potential, pH value, and viscosity were 111.9 ± 0.7 nm, 0.8 ± 0.1 mV, 6.02 ± 0.02, and 12.04 ± 2.64 cP, respectively. This formulation was stable over six months at ambient temperature. The CBD from CBD-β-CDPM-NS rapidly released to 100% within 1 min. Ex vivo permeation studies of CBD-β-CDPM-NS through porcine nasal mucosa revealed a permeation rate of 4.8 μg/cm2/min, which indicated that CBD was effective in penetrating nasal epithelial cells. CBD-β-CDPM-NS was tested for its efficacy and safety in terms of cytokine production from nasal immune cells and toxicity to nasal epithelial cells. The CBD-β-CDPM-NS was not toxic to nasal epithelial at the concentration of CBD equivalent to 3.125–50 μg/mL. When the formulation was subjected to bioactivity testing against monocyte-like macrophage cells, it proved that the CBD-β-CDPM-NS has the potential to inhibit inflammatory cytokines. CBD-β-CDPM-NS demonstrated the formulation's ability to reduce the cytokine produced by S-RBD stimulation in ex vivo porcine nasal mucosa in both preventative and therapeutic modes.

Neomycin: sources of contact and sensitization evaluation in 1162 patients treated at a tertiary service

BackgroundNeomycin is used in several over-the-counter pharmaceutical formulations in Brazil. In Europe and Canada, where it is not freely available, its sensitization frequency is lower than in the United States, where this does not occur. ObjectiveTo present the frequency of sensitization to neomycin observed in a tertiary hospital and the pharmaceutical formulations sold in Brazil containing neomycin. MethodRetrospective analysis of positive results to neomycin, obtained through patch tests performed in a tertiary hospital, from 2009 to 2018 and investigation of topical drugs and vaccines containing neomycin in Brazilian databases available on the internet. ResultsAmong 1,162 patients, 71 (6%) had positive reactions to neomycin, 65% female and 35% male individuals, 46% were over 50 years old, and 24% had a personal history of atopy. The dermatitis lasted from four months to 20 years. Lesions were located in 69% of the patients on the upper limbs, in 55% they were on the lower limbs, and in 42% they were disseminated in more than 4 sites. Polysensitization was detected in 55% of cases. Of these, 28% were linked to sensitization to rubber allergens and 27% to potassium bichromate. A total of 158 topical presentations of neomycin were found: 79 ointments, 58 creams, 10 ophthalmic solutions, seven otological solutions, one oral solution, two nasal solutions, and one antiseptic powder, in addition to 11 types of vaccines. Study limitationsRetrospective study. ConclusionSensitization to neomycin occurred in 6% of the studied population, affecting more females aged over 50 years, with skin lesions located mainly on the upper and lower limbs, in the context of chronic contact dermatitis. Neomycin was found in 135 formulations, most of them available over the counter, as well as in 11 miscellaneous vaccines.