Nasal Formulation Research Articles

Development of mucoadhesive in-situ nasal gel formulation for enhanced bioavailability and efficacy of rizatriptan in migraine treatment

This research article focuses on the development of an in-situ nasal gel formulation for the antimigraine agent, Rizatriptan (RZT), to enhance its bioavailability and efficacy in treating migraine. The aim of the study was to overcome the challenges of rapid mucociliary clearance. Carbopol 934P (1–2 %w/v) was added to the primary solution, followed by HPMC K4M (0.4–1.2 %w/v). Different copolymers were tested, and HPMC K4M was chosen due to its compatibility with the other ingredients. The pH of all formulations was in the nasal pH range, and the drug content was above 97% in all batches. Gelling time varied from 1.3 to 8.6 sec, with low gelling time observed when viscosity and mucoadhesive strength were high. The results were analyzed using a statistical model with interactive and polynomial terms. The statistical analysis showed a good correlation between dependent and independent variables, with R2 values of 0.97758 and 0.948931 for viscosity and mucoadhesive strength, respectively. The Cmax of RZT in the brain was significantly higher (p < 0.05) via intra-nasal (340.27 ng) route as compared to the oral route and the same was the case for AUC. Finally, it was concluded that the RZT nasal in-situ gel system improves bioavailability compared with oral route and could provide fast action in migraine therapy.

RWD44 Use of Real-World Data for Hard-to-Identify Patient Population: Methodology and a Case Study

Real-world data (RWD) provides complimentary and supplemental data to discern effectiveness and value of therapeutic interventions. Fragmented data ecosystems remain a challenge for developing real-world evidence (RWE). In particular, medications dispensed via specialty pharmacies (SP) may not be well captured in traditional claims databases or, if captured, may represent a subgroup of patients. We sought to identify whether tokenization and matching between SP data and administrative claims data was feasible and representative for a nasal formulation of metoclopramide (nasal MCP) using the treatment of for diabetic gastroparesis (DGP).

Development and Evaluation of an FDM Printed Nasal Device for CPZ Solid Nanoparticles.

Nasal drug delivery has been a focus of scientific interest for decades. A number of drug delivery systems and devices are available and have been highly successful in providing better and more comfortable therapy. The benefits of nasal drug delivery are not in question. The nasal surface provides an excellent context for the targeted delivery of active substances. In addition to the large nasal surface area and intensive absorption, the active substances delivered through the nose overcome the blood-brain barrier and can be delivered directly to the central nervous system. Formulations for nasal administration are typically solutions or liquid dispersed systems such as emulsions or suspensions. Formulation techniques for nanostructures have recently undergone intensive development. Solid-phase heterogeneous dispersed systems represent a new direction in pharmaceutical formulations. The wide range of possible examples and the variety of excipients allow for the delivery of a wide range of active ingredients. The aim of our experimental work was to develop a solid drug delivery system that possesses all of the above-mentioned advantageous properties. In developing solid nanosystems, we not only exploited the advantages of size but also the adhesive and penetration-enhancing properties of excipients. During formulation, several amphiphilic compounds with adhesion properties and penetration enhancing effects were incorporated. We used chlorpromazine (CPZ), which is mainly used in the treatment of psychotic disorders such as schizophrenia and bipolar disorder. Chlorpromazine has been previously investigated by our team in other projects. With the availability of previous methods, the analytical characterization of the drug was carried out effectively. Due to the frequent and severe side effects of the drug, the need for therapeutic dose reduction is indisputable. In this series of experiments, we succeeded in constructing drug delivery systems. Finely divided Na nanoparticles were formed using a Büchi B90 nanospray dryer. An important step in the development of the drug carrier was the selection of suitable inert carrier compounds. Particle size determination and particle size distribution analysis were performed to characterize the prepared nanostructures. As safety is the most important aspect of any drug formulation, all components and systems were tested with different biocompatibility assays. The tests performed demonstrated the safe applicability of our systems. The bioavailability of chlorpromazine was studied as a function of the ratio of the active ingredient administered nasally and intravenously. As described above, most nasal formulations are liquids, but our system is solid, so there is currently no tool available to accurately target this system. As a supplement of the project, a nasal dosing device was developed, corresponding to the anatomical structure; a prototype of the device was made using 3D FDM technology. Our results lay the foundation for the design and industrial scaling of a new approach to the design and production of a high-bioavailability nasal medicinal product.

Abstracts from The Aerosol Society Drug Delivery to the Lungs 33.

Abstracts from The Aerosol Society Drug Delivery to the Lungs 33.

(300) Impact of Intranasal Testosterone versus Intramuscular Testosterone cypionate on Hematocrit of Hypogonadal Men: Data from an ongoing Phase IV, Open-label, Randomized Clinical Trial.

Abstract Introduction The potential increase in hematocrit and subsequent risk of polycythemia has been regarded as one of the most worrisome adverse effects of testosterone therapy (TT). Recent evidence has shown that the modality of delivery and half-life of each formulation may affect the incidence of these side effects. Therefore, we hypothesized that longer-acting intramuscular testosterone would increase hematocrit to a higher degree than the shorter-acting nasal formulations that can more closely mimic normal physiology. Objective To compare the effects of Intranasal Testosterone (NT) and Intramuscular Testosterone (TC) on hematocrit and serum testosterone levels in testosterone deficient men over 4 months. Methods This Phase IV, randomized, open-label clinical trial was performed on 39 symptomatic, testosterone deficient (TD) men with at least two serum testosterone levels below 300 ng/dL drawn before 10AM. Men were randomized (1:1) to receive either nasal gel three times per day (5.5mg per nostril) and intramuscular TC (200mg) once every two weeks. The primary outcomes were changes in Hematocrit and serum T before and after four months. Secondary outcomes were changes in estradiol (E), PSA and 17-OHP. Data analysis was performed using two-sample and single-sample T tests (Microsoft Excel v.16.60). Results A total of 39 men with testosterone deficiency were randomized to receive either NT (n=15) or TC (n=24). The median participant age was 46 years old with a mean serum T of 237.1 ng/dL and hematocrit of 43.3%. Prevalence of participants who screened positive for OSA on STOP-BANG questionnaire for NT and TC group were 67% and 71%, respectively. Compared to their respective baselines, men in both groups saw significantly increased serum testosterone levels (p 52%) after 4 months was 0% in NT group and 4.2% in TC. Those taking TC saw increases in E (p=0.003) and decreases in 17-OHP (p&amp;lt;0.001) at follow-up, where NT saw no changes. Neither regimen significantly impacted PSA at follow-up. Conclusions Both Intranasal and Intramuscular testosterone regimens are effective in treating hypogonadal men. However, short-acting nasal T does not appear to impact hematocrit levels especially when compared to testosterone cypionate. Those who are at increased risk of developing polycythemia or want to avoid changes in their E or 17-OHP levels may benefit from short-acting T formulations. Disclosure Yes, this is sponsored by industry/sponsor: Acerus Pharmaceuticals Clarification Industry funding only - investigator initiated and executed study Any of the authors act as a consultant, employee or shareholder of an industry for: Acerus Pharmaceuticals

Donepezil Brain and Blood Pharmacokinetic Modeling after Nasal Film and Oral Solution Administration in Mice.

Intranasal delivery is a non-invasive mode of administration, gaining popularity due to its potential for targeted delivery to the brain. The anatomic connection of the nasal cavity with the central nervous system (CNS) is based on two nerves: olfactory and trigeminal. Moreover, the high vasculature of the respiratory area enables systemic absorption avoiding possible hepatic metabolism. Due to these physiological peculiarities of the nasal cavity, compartmental modeling for nasal formulation is considered a demanding process. For this purpose, intravenous models have been proposed, based on the fast absorption from the olfactory nerve. However, most of the sophisticated approaches are required to describe the different absorption events occurring in the nasal cavity. Donepezil was recently formulated in the form of nasal film ensuring drug delivery in both bloodstream and the brain. In this work, a three-compartment model was first developed to describe donepezil oral brain and blood pharmacokinetics. Subsequently, using parameters estimated by this model, an intranasal model was developed dividing the administered dose into three fractions, corresponding to absorption directly to the bloodstream and brain, as well as indirectly to the brain expressed through transit compartments. Hence, the models of this study aim to describe the drug flow on both occasions and quantify the direct nose-to-brain and systemic distribution.

Exploring the potential of intranasal drug delivery systems in the management of hypertension

Abstract Objectives The current review gives an overview of the anatomical and cellular structure of the nasal cavity. It presents some possibilities and different techniques to enhance the drug penetration through the nasal barrier. It comprehensively details the intranasal drug delivery system and the treatment modalities of hypertension, with an emphasis on nanotechnology-based products. Methods Gather published works about the research progression in the systemic delivery of antihypertensive drugs through the nasal epithelium, the formulation tactics and their related in vitro, ex vivo and in vivo assessment technologies in this field. Key findings Intranasal drug delivery is one of the potential routes for avoiding the first pass effect, lowering drug doses, reducing systemic side effects of most antihypertensive drugs and enhancing drug bioavailability. Conclusions Compared to oral medications, nasal medications often have better bioavailability and fewer adverse effects at the same dosage, which encourages pharmaceutical companies to manufacture additional medications in the form of nasal formulations intended for systemic treatment.

Nano-adjuvanted dry powder vaccine for the mucosal immunization against airways pathogens.

Nasal vaccination has been shown to provide optimal protection against respiratory pathogens. However, mucosal vaccination requires the implementation of specific immunization strategies to improve its effectiveness. Nanotechnology appears a key approach to improve the effectiveness of mucosal vaccines, since several nanomaterials provide mucoadhesion, enhance mucosal permeability, control antigen release and possess adjuvant properties. Mycoplasma hyopneumoniae is the main causative agent of enzootic pneumonia in pigs, a respiratory disease responsible for considerable economic losses in the pig farming worldwide. The present work developed, characterized, and tested in vivo an innovative dry powder nasal vaccine, obtained from the deposition on a solid carrier of an inactivated antigen and a chitosan-coated nanoemulsion, as an adjuvant. The nanoemulsion was obtained through a low-energy emulsification technique, a method that allowed to achieve nano droplets in the order of 200 nm. The oil phase selected was alpha-tocopherol, sunflower oil, and poly(ethylene glycol) hydroxystearate used as non-ionic tensioactive. The aqueous phase contained chitosan, which provides a positive charge to the emulsion, conferring mucoadhesive properties and favoring interactions with inactivated M. hyopneumoniae. Finally, the nanoemulsion was layered with a mild and scalable process onto a suitable solid carrier (i.e., lactose, mannitol, or calcium carbonate) to be transformed into a solid dosage form for administration as dry powder. In the experimental study, the nasal vaccine formulation with calcium carbonate was administered to piglets and compared to intramuscular administration of a commercial vaccine and of the dry powder without antigen, aimed at evaluating the ability of IN vaccination to elicit an in vivo local immune response and a systemic immune response. Intranasal vaccination was characterized by a significantly higher immune response in the nasal mucosa at 7 days post-vaccination, elicited comparable levels of Mycoplasma-specific IFN-γ secreting cells and comparable, if not higher, responsiveness of B cells expressing IgA and IgG in peripheral blood mononuclear cells, with those detected upon a conventional intramuscular immunization. In conclusion, this study illustrates a simple and effective strategy for the development of a dry powder vaccine formulation for nasal administration which could be used as alternative to current parenteral commercial vaccines.

Gender differences in response and remission rates among patients receiving esketamine

IntroductionDepressive disorders are among the leading causes of disability. The lifetime risk for developing clinically significant depression is estimated around 15%. Multiple studies have found female-male ratio of 2:1 across nations and cultures. The reason for this marked difference is still not clear, although several theories addressing social, biological, and environmental contributors have been suggested. Respond to anti-depressant treatment is considerably similar in both genders. However, several studies have shown worse outcomes among women during menopause.In 2019, the US Food and Drug Administration (FDA) approved a nasal spray formulation of esketamine for the treatment of resistant depression (TRD) in adults, and the treatment has been approved to use by the ministry of health in Israel since 2020 . Recent studies found more than 50% response and 35% remission rates, when nasal esketamine was given as an add-on therapy.Objectivesto assess gender differences in response and remission rates among patients receiving esketamine as an add-on therapy for TRD in a real-world settingMethods23 female and 22 males received at least 12 weeks of esketamine treatment in a day-care setting. Data collected included depression, dissociation and quality of life scales.ResultsFemales tend to experience more severe dissociation during treatment. Average response and remission rates were similar in both groups (48% and 32% respectively), however females were less favorable to show rapid response (during the first 4 weeks). among responders no major differences in time to response has been found.Conclusionsno major gender differences in response or remission rates have been found among patients receiving esketamine treatment for TRD aside from lower rates of rapid response. Additionally, Females report more severe dissociation during treatment.Disclosure of InterestNone Declared

Engineering of Lurasidone Hydrochloride Loaded Niosomes for Enhancing the Antipsychotic Potential for Nasal Administration

Background: Drugs having high first-pass metabolism or that are susceptible to enzymatic degradation can be administered through the nasal route to avoid their degradation. Lurasidone exhibits less toxicity and side effects as compared to its sister drugs like risperidone, ziprasidone, clozapine, etc. Objectives: The present study aimed to develop Lurasidone loaded niosomes for nasal delivery. Methods: Lurasidone niosomes were developed by adapting the ether injection method and optimized using a central composite design. In vitro and in vivo studies were conducted using optimized formulation. Results: The findings showed that the optimized formulation exhibited a particle size of 159.02 ± 0.58 nm and an entrapment efficiency of 91.6 ± 1.6%. The findings from the nasal histopathological analysis revealed that the optimized formulation was non-irritant and non-toxic for nasal mucosa. The findings from in vitro studies revealed 94.61 ± 0.27% of drug release from optimized formulation F7 throughout 24 hrs. The findings of in vivo (Albino Wistar rats) studies demonstrated that various pharmacokinetic parameters (Cmax, Tmax, AUC(0-24), T1/2, Vd and Cl) and pharmcodynamic parameters (conditioned avoidance response, biochemical estimation using oxidative markers such as superoxide dismutase, malondialdehyde and glutathione) were significantly improved compared to marketed tablets (Lurasid® 40 mg) and pure drug suspension. Optimized formulation F-7 exhibited 4.9 times more bioavailability than that of pure drug suspension following intranasal administration. Conclusion: These findings indicate that nasal niosomal formulation of Lurasidone HCl is a promising nanoplatform for enhancing the overall performance of Lurasidone. These results could open new avenues into the future of nanomedicine.

Combination of Cellulose Derivatives and Chitosan-Based Polymers to Investigate the Effect of Permeation Enhancers Added to In Situ Nasal Gels for the Controlled Release of Loratadine and Chlorpheniramine.

The purpose of the study is to develop and assess mucoadhesive in situ nasal gel formulations of loratadine and chlorpheniramine maleate to advance the bioavailability of the drug as compared to its conventional dosage forms. The influence of various permeation enhancers, such as EDTA (0.2% w/v), sodium taurocholate (0.5% w/v), oleic acid (5% w/v), and Pluronic F 127 (10% w/v), on the nasal absorption of loratadine and chlorpheniramine from in situ nasal gels containing different polymeric combinations, such as hydroxypropyl methylcellulose, Carbopol 934, sodium carboxymethylcellulose, and chitosan, is studied. Among these permeation enhancers, sodium taurocholate, Pluronic F127 and oleic acid produced a noticeable increase in the loratadine in situ nasal gel flux compared with in situ nasal gels without permeation enhancer. However, EDTA increased the flux slightly, and in most cases, the increase was insignificant. However, in the case of chlorpheniramine maleate in situ nasal gels, the permeation enhancer oleic acid only showed a noticeable increase in flux. Sodium taurocholate and oleic acid seems to be a better and efficient enhancer, enhancing the flux > 5-fold compared with in situ nasal gels without permeation enhancer in loratadine in situ nasal gels. Pluronic F127 also showed a better permeation, increasing the effect by >2-fold in loratadine in situ nasal gels. In chlorpheniramine maleate in situ nasal gels with EDTA, sodium taurocholate and Pluronic F127 were equally effective, enhancing chlorpheniramine maleate permeation. Oleic acid has a better effect as permeation enhancer in chlorpheniramine maleate in situ nasal gels and showed a maximum permeation enhancement of >2-fold.

Safety in Rats of a Novel Nasal Spray Formulation for the Prevention of Airborne Viral Infections.

Hexedra+® is a nasal spray containing hydroxypropyl methylcellulose, beta-cyclodextrin, and usnic acid. It has been developed with the aim of reducing the risk of transmission of airborne viral infections, with particular reference to influenza and COVID-19. As part of the preclinical development of the product, we carried out a study on thirty male Wistar rats divided into three study groups and treated with Hexedra+, an alternative formulation containing a double concentration of usnic acid (0.015% instead of 0.0075%) or saline solution. Products were administered at the dose of 30 μL into each nostril, three times a day for seven consecutive days by means of a micropipette. By the end of the treatment period, no significant changes were observed in body weight. Histological examination of nasal mucosa and soft organs did not show any significant difference in the three study groups. Serum transaminase level remained in the normal limit in all the animals treated. The serum level of usnic acid was measured in order to assess the absorption of the molecule through the nasal mucosa. By the end of the study period, the usnic acid serum level was negligible in all the animals treated. In conclusion, the safety profile of Hexedra+ appears favorable in the animal model studied.

Обзор назальных средств для профилактики и терапии воздушно-капельных инфекций

Airborne infections constitute an extensive group of human diseases. The first barrier to the penetration of infectious agents is the oropharyngeal mucosa, where the autonomic immune system plays a special role. Therefore, maintaining the active function of mucosal immunity and its correction in situ, in the focus of inflammation, is an important way to stop respiratory infections. The coronavirus pandemic has spurred the search for effective means of preventing and treating viral diseases. Various nasal formulations have been proposed with barrier, virucidal, anti-inflammatory and antibacterial properties. An important place belongs to antibodies directed against a specific pathogen, for which it is proposed to use monoclonal antibodies, antibodies isolated from eggs of immunized chickens, nano-antibodies of representatives of the Camelid family, or colostrum antibodies of vaccinated cows. In our opinion, it is more attractive to use antibodies isolated from human blood plasma, which have a wide spectrum of activity, therefore, in the case of mixed infection or difficult diagnosis, they can have a preventive or therapeutic effect against many pathogens. Nasal drops or spray containing human immunoglobulin can be an effective treatment for many bacterial and viral infections, including COVID-19. Key words: аirborne infections, COVID-19, prevention, nasal drugs, antibodies, human immunoglobulin

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.

SIMULTANEOUS REVERSE PHASE-HIGH PERFORMANCE LIQUID CHROMATOGRAPHY (RP-HPLC) ESTIMATION OF AZELASTINE HYDROCHLORIDE, FLUTICASONE PROPIONATE, AND PHENYL ETHYL ALCOHOL IN DYMISTA (MEDA) NASAL SPRAY

This work reported a reverse phase-high performance liquid chromatography method for quantitative estimation of Azelastine Hydrochloride, Fluticasone Propionate, and Phenylethyl Alcohol in Nasal Spray formulation. The assay involved an isocratic elution of these components by using Intersil Octadecylsilane (C18) column (25 cm x 4.6 mm x 5 μm) using mobile phase composition of Buffer: Solvent Mixture (40:60 %v/v) and pH adjusted to 6.5 with dilute orthophosphoric acid. The flow rate was 1.4 mLmin-1 and the analytes are monitored at 254 nm. Separation was completed within 20 minutes. Calibration curves were linear with correlation coefficient more than 0.99 over a concentration range of 50%, 75%, 100%, 125%, and 150% for Azelastine Hydrochloride, Fluticasone Propionate and Phenylethyl Alcohol. The method was proven to be accurate between 50 to 150% with 98 to 102 % recovery of the actives from a spiked placebo. The method was shown to be precise yielding acceptable results for the system reproducibility and method repeatability. All the validation parameters were within the acceptance range according to International Conference on Harmonization norms. The developed method is simple and rapid which could be applied for routine estimation of the formulation.

The nose has it: Opportunities and challenges for intranasal drug administration for neurologic conditions including seizure clusters.

Nasal administration of treatments for neurologic conditions, including rescue therapies to treat seizure clusters among people with epilepsy, represents a meaningful advance in patient care. Nasal anatomy and physiology underpin the multiple advantages of nasal administration but also present challenges that must be addressed in any successful nasal formulation. Nasal cavity anatomy is complex, with a modest surface area for absorption that limits the dose volume of an intranasal formulation. The mucociliary clearance mechanism and natural barriers of the nasal epithelia must be overcome for adequate absorption. An extensive vasculature and the presence of olfactory nerves in the nasal cavity enable both systemic and direct-to-brain delivery of drugs targeting the central nervous system. Two intranasal benzodiazepine rescue therapies have been approved by the US Food and Drug Administration for seizure-cluster treatment, in addition to the traditional rectal formulation. Nasal sprays are easy to use and offer the potential for quick and consistent bioavailability. This review aims to increase the clinician's understanding of nasal anatomy and physiology and of the formulation of intranasal rescue therapies and to facilitate patient education and incorporate intranasal rescue therapies for seizure clusters (also known as acute repetitive seizures) into their seizure action plans.

Formulation and characterization of lamotrigine nasal insert targeted brain for enhanced epilepsy treatment

Lamotrigine. (LMT) is a triazine drug has an antiepileptic effect but with low water solubility, dissolution rate and thus therapeutic effect. Spanlastics are nano-vesicular carriers’ act as site-specific drug delivery system. Intranasal route could direct the drug from nose to brain and provide a faster and more specific therapeutic effect. Therefore, this study aimed to upload lamotrigine onto nano-vesicles using spanlastic nasal insert delivery for effective epilepsy treatment via overcoming lamotrigine’s low solubility and improving its bioavailability. Lamtrigine-loaded nano-spanlastic vesicles were prepared by ethanol injection method. To study different formulation factor’s effect on formulations characters; particle size (PS), Zeta potential (ZP), polydispersity index (PDI), entrapment efficiency percentage (EE%) and LMT released amount after 6 h (Q6h); 2^1 and 3^1 full factorial designs were employed. Optimized formula was loaded in lyophilized nasal inserts formulation which were characterized for LMT release and mucoadhesion. Pharmacokinetics studies in plasma and brain were performed on rats to investigate drug targeting efficiency. The optimal nano-spanlastic formulation (F4; containing equal Span 60 amount (100 mg) and edge activator; Tween 80) exhibited nano PS (174.2 nm), high EE% (92.75%), and Q6h > 80%. The prepared nasal inserts (S4) containing 100 mg HPMC has a higher mucoadhesive force (9319.5 dyne/cm2) and dissolution rate (> 80% within 10 min) for rapid in vivo bio-distribution. In vivo studies showed considerable improvement brain and plasma’s rate and extent absorption after intranasal administration indicating a high brain targeting efficiency. The results achieved indicate that nano-spanlastic nasal-inserts offer a promising LMT brain targeting in order to maximize its antiepileptic effect.

Chlorine counterion effect into the supramolecular arrangement of phenylephrine solid state

Phenylephrine is widely used as a nasal and mydriatic decongestant in various nasal and ophthalmic formulations. Phenylephrine is traditionally commercialized in its saline form as phenylephrine hydrochloride. Due to changes in crystalline packing, counterion inclusion affects the chemical, physical, biological properties, and reactivity. Structural, topological, and energy analyses are essential to compare and understand those changes in physicochemical properties and their impacts on drug production. This study evaluates the conformational changes, crystalline packaging, and interactions of phenylephrine and phenylephrine hydrochloride. Theoretical calculations were used to assess the stability and supramolecular arrangement. The energetic gap ΔELUMO-HOMO shows that the Cl– counterion provides greater stability for phenylephrine. Phenylephrine exhibits a more significant number of interactions O···O and O···H that increase hygroscopicity and chemical reactivity of a compound. The presence of the counterion alters the conformational and structural properties of phenylephrine, causing changes in its properties and influencing its use.

In vitro interactions of aerosol formulations with human nasal epithelium using real-time monitoring of drug transport in a nasal mucosa-on-a-chip

The current organ-on-chip platforms used for studying respiratory drug delivery are limited to the administration of drug solutions and suspensions, lacking the in vivo aerosol drug administration and aerosol interaction with the respiratory tract barrier. Moreover, they mostly rely on conventional assays that require sample collection and ‘off the chip’ analyses, which can be labor-intensive and costly. In this study, a human nasal epithelial mucosa (NEM)-on-a-chip is developed that enables the deposition of aerosolized nasal formulations while emulating realistic shear stresses (0.23 and 0.78 Pa), exerted to the inferior and middle turbinate of the human nasal cavity. Under these different dynamic conditions in the donor channel of the NEM-on-a-chip, the deposited dose of aerosols and particle size distributions varied. In addition, the increase in the shear stress to 0.78 Pa adversely affected the cells' viability, reflected by a 36.9 ± 5.4% reduction in the transepithelial electrical resistance. The epithelial transport profiles of aerosolized ibuprofen formulations under 0.23 Pa shear stress were successfully monitored in real-time by an electrochemical sensor embedded in the acceptor channel, where the NEM-on-a-chip was able to monitor the effect of permeation enhancer in the test formulation on the rate of drug transport. The novel NEM-on-a-chip can potentially be a promising physiologically relevant tool for reliable nasal aerosol testing in vitro.

Nasalferon, a new nasal formulation of IFNα2b, modulates cellular and molecular elements associated with an antiviral response in mucosa and blood

We conducted an experimental protocol with a nasal recombinant IFNα-2b formulation (Nasalferon) in 12 healthy volunteers who received 1 MIU per nostril twice a day, three consecutive days, and studied the induction of biomarkers related to antiviral and immune responses. Nasalferon increases the antiviral biomarker OAS1 transcript levels in oropharynx and PBMCs, regulates molecular and cellular elements related to innate and adaptive immune responses and decreases granulocytes population. These effects support Nasalferon use in virally-exposed populations.