Intranasal Drug Administration Research Articles

Comparison of the effects of intranasal and intramuscular midazolam–butorphanol–ketamine on intraocular pressure, tear production and sedation in New Zealand White rabbits

ObjectiveTo compare the effects of intranasal (IN) and intramuscular (IM) midazolam–butorphanol–ketamine on intraocular pressure (IOP), tear production (TP) and sedation in rabbits. Study designProspective, randomized, crossover experimental study. AnimalsFourteen male New Zealand White rabbits, aged 1–2 years, body mass 3.1 ± 0.8 kg (mean ± standard deviation). MethodsRabbits were administered midazolam (1 mg kg–1), butorphanol (1.5 mg kg–1) and ketamine (5 mg kg–1) via IN and IM routes. IOP, TP and sedation scores were assessed at 0 (before drug administration), 5, 15, 30, 45 and 60 minutes after drug administration. Heart rate (HR), respiratory rate (fR), rectal temperature (RT), noninvasive mean arterial blood pressure (MAP) and peripheral hemoglobin oxygen saturation (SpO2) were simultaneously recorded until 45 minutes after drug administration. The onset and duration of sedation and sedation scores were recorded. ResultsDrug delivery route had no significant impact on mean IOP (p = 0.271) or TP (p = 0.062), and there were no significant changes over time for IOP (p = 0.711) or TP (p = 0.372). Similarly, delivery route had no significant impact on HR (p = 0.747), fR (p = 0.872), RT (p = 0.379), MAP (p = 0.217) and SpO2 (p = 0.254). Sedation onset was faster with IN (3.0 ± 1.0 minutes) than with IM administration (4.9 ± 0.7 minutes) (p = 0.011), but sedation duration was significantly longer with IM (52.6 ± 7.2 minutes) than with IN delivery (30.7 ± 6.8 minutes) (p = 0.004). There was no significant difference in sedation scores between the two delivery routes at any of the recorded time points. Conclusions and clinical relevanceThe combination of midazolam–butorphanol–ketamine had minimal impact on physiological and ocular variables regardless of the route of administration, whereas IN drug administration led to a shorter onset and duration of action than IM administration.

Intranasal Therapy in Palliative Care.

In recent years, the use of the intranasal route has been actively explored as a possible drug delivery method in the palliative patient population. There are reports demonstrating the effectiveness of nasally administered medications that are routinely used in patients at the end of life. The subject of this study is the intranasal drug administration among palliative patients. The aim is to summarize currently used intranasal therapies among palliative patients, determine the benefits and difficulties, and identify potential areas for future research. A review of available medical literature published between 2013 and 2023 was performed using online scientific databases. The following descriptors were used when searching for articles: "palliative", "intranasal", "nasal", "end-of-life care", "intranasal drug delivery" and "nasal drug delivery". Out of 774 articles, 55 directly related to the topic were finally selected and thoroughly analyzed. Based on the bibliographic analysis, it was shown that drugs administered intranasally may be a good, effective, and convenient form of treatment for patients receiving palliative care, in both children and adults. This topic requires further, high-quality clinical research.

CNS Drug Delivery in Stroke: Improving Therapeutic Translation From the Bench to the Bedside.

Drug development for ischemic stroke is challenging as evidenced by the paucity of therapeutics that have advanced beyond a phase III trial. There are many reasons for this lack of clinical translation including factors related to the experimental design of preclinical studies. Often overlooked in therapeutic development for ischemic stroke is the requirement of effective drug delivery to the brain, which is critical for neuroprotective efficacy of several small and large molecule drugs. Advancing central nervous system drug delivery technologies implies a need for detailed comprehension of the blood-brain barrier (BBB) and neurovascular unit. Such knowledge will permit the innate biology of the BBB/neurovascular unit to be leveraged for improved bench-to-bedside translation of novel stroke therapeutics. In this review, we will highlight key aspects of BBB/neurovascular unit pathophysiology and describe state-of-the-art approaches for optimization of central nervous system drug delivery (ie, passive diffusion, mechanical opening of the BBB, liposomes/nanoparticles, transcytosis, intranasal drug administration). Additionally, we will discuss how endogenous BBB transporters represent the next frontier of drug delivery strategies for stroke. Overall, this review will provide cutting edge perspective on how central nervous system drug delivery must be considered for the advancement of new stroke drugs toward human trials.

Hypothalamic circuits and aging: keeping the circadian clock updated.

Over the past century, age-related diseases, such as cancer, type-2 diabetes, obesity, and mental illness, have shown a significant increase, negatively impacting overall quality of life. Studies on aged animal models have unveiled a progressive discoordination at multiple regulatory levels, including transcriptional, translational, and post-translational processes, resulting from cellular stress and circadian derangements. The circadian clock emerges as a key regulator, sustaining physiological homeostasis and promoting healthy aging through timely molecular coordination of pivotal cellular processes, such as stem-cell function, cellular stress responses, and inter-tissue communication, which become disrupted during aging. Given the crucial role of hypothalamic circuits in regulating organismal physiology, metabolic control, sleep homeostasis, and circadian rhythms, and their dependence on these processes, strategies aimed at enhancing hypothalamic and circadian function, including pharmacological and non-pharmacological approaches, offer systemic benefits for healthy aging. Intranasal brain-directed drug administration represents a promising avenue for effectively targeting specific brain regions, like the hypothalamus, while reducing side effects associated with systemic drug delivery, thereby presenting new therapeutic possibilities for diverse age-related conditions.

Atomized Intranasal Ketorolac Versus Intravenous Ketorolac for the Treatment of Severe Renal Colic in the Emergency Department: A Double-Blind, Randomized Controlled Trial

Atomized intranasal (IN) drug administration offers an alternative to the intravenous (IV) route. We aimed to evaluate the analgesic efficacy of IN versus IV ketorolac in emergency department patients with acute renal colic. We conducted a double-blind, randomized controlled trial on adult patients (aged 18 to 64 years) with severe renal colic and numerical rating scale pain ratings ≥7.0. They were randomly assigned (1:1) to receive single doses of either IN or IV ketorolac. Our main outcomes were differences in numerical rating scale reduction at 30 and 60 minutes. A 95% confidence interval (CI) was calculated for each mean difference, with a minimum clinically important difference set at 1.3 points. Secondary outcomes included treatment response, adverse events, rescue medications, and emergency department revisits. We analyzed using intention-to-treat. A total of 86 and 85 patients with similar baseline characteristics were allocated to the IV and IN groups, respectively. Mean numerical rating scale scores were 8.52 and 8.65 at baseline, 3.85 and 4.67 at 30 minutes, and 2.80 and 3.04 at 90 minutes, respectively. The mean numerical rating scale reduction differences between the IV and IN groups were 0.69 (95% CI -0.08 to 1.48) at 30 minutes and 0.10 (95% CI -0.85 to 1.04) at 60 minutes. There were no differences in secondary outcomes. Neither IN or IV ketorolac was superior to the other for the treatment of acute renal colic, and both provided clinically meaningful reductions in pain scores at 30 to 60 minutes.

Intranasal drug delivery in pediatric emergency departments: brief review and future outlook

This review aims to provide an overview and update of current literature on the use of intranasal (IN) drug delivery in pediatric emergency medicine (PEM), in terms of the anatomy, physiology, pharmacokinetics, limitations, drug delivery methods, necessary training, safety, contraindications, effectiveness, current indications and trends, and implications for clinical practice and future developments in IN drug administration. We evaluate how IN medication use in PEM has recently evolved, what recent research has revealed about the utility of IN drug delivery in PEM, and what the future of IN drug delivery might look like.

Utility of a Novel Micro-Spraying Device for Intranasal Administration of Drug Solutions to Mice.

Intranasal administration has attracted attention as a means of delivering drugs because it bypasses the blood-brain barrier. However, conventional intranasal administration of drug solutions to mice using the micropipette method (MP method) is complicated and time-consuming because it requires small doses to be administered under inhalation anesthesia. This study evaluated the effectiveness of a novel intranasal administration method using Micro FPS™, a novel micro-spraying device (the MSD method). The MSD method allowed more reliable administration of the solution to the nasal mucosa than the MP method did. The transfer of inulin, a model water-soluble macromolecule compound, to the olfactory bulb and brain (cerebrum, cerebellum, brainstem, and striatum) was similar with the two methods. It also allowed the drug to be administered in a shorter time. These results suggest that the MSD method is simpler and more rapid than the MP method for intranasal administration of drugs to mice and achieves comparable delivery of inulin to the olfactory bulb and brain. Therefore, the Micro FPS™ device is a potentially useful tool for intranasal drug administration to rodents and could facilitate the development of intranasal formulations, contributing to drug development for central nervous system diseases.

Porous silicon embedded in a thermoresponsive hydrogel for intranasal delivery of lipophilic drugs to treat rhinosinusitis

Intranasal delivery is the most preferred route of drug administration for treatment of a range of nasal conditions including chronic rhinosinusitis (CRS), caused by an infection and inflammation of the nasal mucosa. However, localised delivery of lipophilic drugs for persistent nasal inflammation is a challenge especially with traditional topical nasal sprays. In this study, a composite thermoresponsive hydrogel is developed and tuned to obtain desired rheological and physiochemical properties suitable for intranasal administration of lipophilic drugs. The composite is comprised of drug-loaded porous silicon (pSi) particles embedded in a poloxamer 407 (P407) hydrogel matrix. Mometasone Furoate (MF), a lipophilic corticosteroid (log P of 4.11), is used as the drug, which is loaded onto pSi particles at a loading capacity of 28 wt%. The MF-loaded pSi particles (MF@pSi) are incorporated into the P407-based thermoresponsive hydrogel (HG) matrix to form the composite hydrogel (MF@pSi-HG) with a final drug content ranging between 0.1 wt% to 0.5 wt%. Rheomechanical studies indicate that the MF@pSi component exerts a minimal impact on gelation temperature or strength of the hydrogel host. The in-vitro release of the MF payload from MF@pSi-HG shows a pronounced increase in the amount of drug released over 8 h (4.5 to 21-fold) in comparison to controls consisting of pure MF incorporated in hydrogel (MF@HG), indicating an improvement in kinetic solubility of MF upon loading into pSi. Ex-vivo toxicity studies conducted on human nasal mucosal tissue show no adverse effect from exposure to either pure HG or the MF@pSi-HG formulation, even at the highest drug content of 0.5 wt%. Experiments on human nasal mucosal tissue show the MF@pSi-HG formulation deposits a quantity of MF into the tissues within 8 h that is >19 times greater than the MF@HG control (194 ± 7 μg of MF/g of tissue vs. <10 μg of MF/g of tissue, respectively).

Effect of ayurvedic interventions in the management of allergic rhinitis - An open label multi-centre single arm clinical study

Abstract BACKGROUND: The symptoms of Allergic Rhinitis,resemble the clinical presentation of Vataja Pratishyaya, a type of Pratishyaya, narrated in the Ayurveda classical texts. An exploratory clinical study was planned to assess the the safety and potential effect of a combination therapy of Ayurveda interventions, viz., Ayush VPR (a coded Ayurvedic formulation), Shirishadi Kwath (Anubhoota Yoga), and Nasya (intranasal drug administration) with Anutaila. MATERIALS AND METHODS: The study was an open-label, multicenter, prospective clinical study with pre-test and post-test design. Sixty participants aged between 18 and 65 years with the symptoms of AR were enrolled in the study as per the inclusion and exclusion criteria. The interventions given to the participants were Ayush VPR (3.5 g) powder, twice a day with honey and ghee after food, Shirishadi Kwath (20 ml) twice a day, orally on an empty stomach, and Anutaila Nasya (intranasal drug administration) for 7 days for two consecutive cycles with an interval of 7 days. The participants were assessed weekly for a total duration of 28 days. This was followed by a 28-day follow-up period, with assessments conducted at intervals of 14 days. The primary outcome was change in the CARAT (Control of Allergic Rhinitis and Asthma Test) score. RESULTS: Data of 60 participants were used for analysis. The mean age of participants was 35.8 ± 12.12., and the proportion of males and females were comparable with 51.7% females among the total participants. The mean CARAT score improved from baseline to the subsequent follow-ups at 7th, 14th, 21st, and 28th days. A significant improvement in the mean total CARAT score (P &lt; 0.001) was observed after the 28th day of treatment and also at the end of the 56th day in comparison to baseline. CONCLUSION: The Ayurvedic formulations, Shirishadi Kwath, Ayush VPR, and Anutaila, are safe and significantly reduce rhinorrhea, nasal itching, sneezing fits, nasal congestion, and nasal obstruction. The present study reveals that the Ayurvedic treatment provided highly significant relief from AR.

A Biodegradable, Adhesive, and Stretchable Hydrogel and Potential Applications for Allergic Rhinitis and Epistaxis.

Bioadhesive hydrogels have attracted considerable attention as innovative materials in medical interventions and human-machine interface engineering. Despite significant advances in their application, it remains critical to develop adhesive hydrogels that meet the requirements for biocompatibility, biodegradability, long-term strong adhesion, and efficient drug delivery vehicles in moist conditions. A biocompatible, biodegradable, soft, and stretchable hydrogel made from a combination of a biopolymer (unmodified natural gelatin) and stretchable biodegradable poly(ethylene glycol) diacrylate is proposed to achieve durable and tough adhesion and explore its use for convenient and effective intranasal hemostasis and drug administration. Desirable hemostasis efficacy and enhanced therapeutic outcomes for allergic rhinitis are accomplished. Biodegradation enables the spontaneous removal of materials without causing secondary damage and minimizes medical waste. Preliminary trials on human subjects provide an essential foundation for practical applications. This work elucidates material strategies for biodegradable adhesive hydrogels, which are critical to achieving robust material interfaces and advanced drug delivery platforms for novel clinical treatments.

Recent Approaches of Intranasal to Brain Drug Delivery System

While the intranasal administration of drugs to the brain has been gaining both research attention and regulatory success over the past several years, key fundamental and translational challenges remain to fully leveraging the promise of this drug delivery pathway for improving the treatment of various neurological and psychiatric illnesses. In response, this review highlights the current state of understanding of the nose-to-brain drug delivery pathway and how both biological and clinical barriers to drug transport using the pathway can been addressed, as illustrated by demonstrations of how currently approved intranasal sprays leverage these pathways to enable the design of successful therapies. Moving forward, aiming to better exploit the understanding of this fundamental pathway, we also outline the development of nanoparticle systems that show improvement in delivering approved drugs to the brain and how engineered nanoparticle formulations could aid in breakthroughs in terms of delivering emerging drugs and therapeutics while avoiding systemic adverse effects.

Intranasal nanotherapeutics for brain targeting and clinical studies in Parkinson's disease.

Parkinson's disease (PD) is the second leading neurodegenerative disease globally, impacting the quality of life of a large population. Millions of people are affected by PD, and it is estimated that the treatment cost of PD in the USA can rise to 79 billion dollars by 2037. Limited drugs are approved by USFDA, which only provides systematic relief. Further, the drug efficacy is challenged due to low drug-brain concentration due to first-pass metabolism and blood-brain barrier (BBB). Intranasal drug administration can offer several advantages over systemic administration for efficient brain delivery. Nose-to-brain (N2B) drug delivery can enhance brain bioavailability, reduce enzymatic degradation, and reduce systemic adverse effects. However, due to poor absorption from the nasal mucosa, intranasal administration can be challenging for hydrophilic drugs. The drug mucociliary clearance, retention time, and nasal enzymatic degradation can also affect N2B drug delivery. Nanocarriers can enhance residence time, improve nasal permeation, increase brain uptake, and reduce enzymatic degradation. This review discusses the roles and applications of various N2B nanocarriers to treat PD effectively and clinical trials of antiparkinson molecules. Lastly, safety aspects and prospects of potential nanotherapeutics for the effective treatment of PD are discussed.

Recent Developments In Brain-Targeted Drug Delivery Systems via Intranasal Route

Diseases of the human nervous system such as neurological infections, Parkinson's, Alzheimer's, and other neurodegenerative diseases are severe pathological diseases and become a public health problem. Neurological disease in its treatment requires a drug distribution mechanism to reach the brain in sufficient quantities so that therapeutic effectiveness is achieved. This is very difficult to achieve with conventional treatment methods such as oral and injection because there are several obstacles in the process of drug distribution, one of which is an obstacle in the form of a Blood Brain Barrier (BBB). Along with current therapeutic developments, drug delivery modifications in the pharmaceutical field are increasingly being developed for the treatment of central nervous system (CNS) diseases. The intranasal drug delivery system to the brain via the nose is very interesting because this route can deliver drugs directly to the brain via the BBB. The intranasal route is preferred in brain targeting. This is due to the ability of the intranasal route to directly deliver drugs through the neural pathways, namely the olfactory nerve and the trigeminal nerve. By distributing the drug via the intranasal route, the drug will pass through the BBB and not undergo metabolism in the liver (first-pass metabolism), where this condition is a barrier that significantly inhibits the peripheral transport of drugs to the brain. There are several things that influence intranasal drug delivery, including parameters that affect intranasal drug administration, drug administration pathways, and mechanisms from the nose to the brain. An in vitro system that can be used to determine the permeability of drugs by means of nano and microparticles through olfactory mucosa cells. Positive results from in vitro experiments on rat test animals indicate that intranasal drug distribution guarantees the effectiveness of nanoparticle formulations in drug therapy. Seeing the big influence on the effectiveness of treatment methods in neurological diseases that must pass through the barrier in the form of the BBB, it is necessary to have further studies related to developing drug delivery via the intranasal route.

Crosslinked Chitosan Nanoparticles with Muco-Adhesive Potential for Intranasal Delivery Applications.

Intranasal drug delivery is convenient and provides a high bioavailability but requires the use of mucoadhesive nanocarriers. Chitosan is a well-established polymer for mucoadhesive applications but can suffer from poor cytocompatibility and stability upon administration. In this work, we present a method to obtain stable and cytocompatible crosslinked chitosan nanoparticles. We used 2,6-pyridinedicarboxylic acid as a biocompatible crosslinker and compared the obtained particles with those prepared by ionotropic gelation using sodium tripolyphosphate. Nanoparticles were tested to evaluate the size and the surface charge, as well as their stability in storage conditions (4 °C), at the nasal cavity temperature (32 °C), and at the body temperature (37 °C). The crosslinked chitosan nanoparticles showed a size around 150 nm and a surface charge of 10.3 mV ± 0.9 mV, both compatible with the intranasal drug administration. Size and surface charge parameters did not significantly vary over time, indicating the good stability of these nanoparticles. We finally tested their cytocompatibility in vitro using SHSY5Y human neuroblastoma and RPMI 2650 human nasal epithelial cells, with positive results. In conclusion, the proposed synthetic system shows an interesting potential as a drug carrier for intranasal delivery.

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.

Intranasally administered thermosensitive gel for brain-targeted delivery of rhynchophylline to treat Parkinson’s disease

The aim of this study is to overcome the obstacle of the blood-brain barrier (BBB) in therapeutic drugs of Parkinson's disease (PD), like rhynchophylline (RIN) entry by intranasal administration and to solve the problem of short residence time of drugs in the nasal cavity by the dosage form design of thermosensitive gel. We first conducted a study of the screening of absorption enhancers and 3% hydroxypropyl-β-cyclodextrin (HP-β-CD) was effective to improve the nasal mucosal permeability of RIN. By adjusting the ratio of different components in order to make the gel with adhesion and rapid gelation which were determined to be Poloxamer 407 (P407) 20%, Poloxamer 188 (P188) 1%, polyethylene glycol 6000 (PEG-6000) 1% and HP-β-CD 3%. In addition, the characterization showed that the thermosensitive gel was network cross-linked, rapidly gelation upon entry into the nasal cavity and was stable as semi-solid state with adhesion as well as sustained release properties. Moreover, pharmacokinetic study was performed to evaluate the bioavailability and brain targeting of RIN thermosensitive gel and which were 1.6 times and 2.1 times higher than those of oral administration. We also evaluated the anti-PD effects of RIN thermosensitive gel in-vitro as well as in-vivo. The results showed that RIN thermosensitive gel was effective in repairing the motor function impairment, dysregulated expression levels of oxidative stress factors, and positive neuronal damage within the substantia nigra and dopamine caused by PD. The constructed intranasal drug administration strategy through thermosensitive gel provided a new choice for targeted treatment of PD together with other central nervous system diseases.

Combined use of intranasal Dexmedetomidine and an oral novel formulation of Midazolam for sedation of young children during brain MRI examination: a prospective, single-center, randomized controlled trial

BackgroundTo evaluate the safety and effectiveness of different dosages of intranasal Dexmedetomidine (DEX) in combination with oral midazolam for sedation of young children during brain MRI examination.MethodsIncluded in this prospective single-blind randomized controlled trial were 156 children aged from 3 months to 6 years and weighing from 4 to 20 Kg with ASA I-II who underwent brain MRI examination between March 2021 and February 2022. Using the random number table method, they were divided into group A (using 3 ug/kg intranasal DEX plus 0.2 mg/Kg oral midazolam) and group B (using 2 ug/kg intranasal DEX plus 0.2 mg/Kg oral Midazolam). The one-time success rate of sedation, sedation onset time, recovery time, overall sedation time, and occurrence of adverse reactions during MRI examination were compared between the two groups. The heart rate (HR), mean arterial pressure (MAP), and percutaneous SpO2before and after drug administration were observed in both groups. Differences in sedation scores between the two groups were compared before intranasal drug administration (T0), 10 min after drug administration (T1), at the time of falling asleep (T2), at the end of examination (T3), and at the time of recovery (T4).ResultsThe one-time success rate of sedation in group A and B was 88.31% and 79.75% respectively, showing no significant difference between the two groups (P>0.05). The sedation onset time in group A was 24.97±16.94 min versus 27.92±15.83 min in group B, and the recovery time was 61.88±22.18 min versus 61.16±28.16 min, both showing no significance difference between the two groups (P>0.05). Children in both groups exhibited good drug tolerance without presenting nausea and vomiting, hypoxia, or bradycardia and hypotension that needed clinical interventions. There was no significant difference in the occurrence of abnormal HR, MAP or other adverse reactions between the two groups (P>0.05).Conclusion3 ug/kg or 2 ug/kg intranasal DEX in combination with 0.2 mg/kg oral Midazolam both are safe and effective for sedation of children undergoing MRI examination with the advantages of fast-acting and easy application.Trial registrationIt was registered at the Chinese Clinical Trial Registry (ChiCTR1800015038) on 02/03/2018.

Comparative efficacy of three different doses of intranasal dexmedetomidine for premedication in children

Preoperative emotional distress in children should be addressed properly for better anesthetic experience. The present study was a Prospective randomized double-blind study to evaluate comparative efficacy of three different doses of intranasal dexmedetomidine for premedication in children. Sixty children were then randomly allocated to one of the three groups of 20 each by a computer generated table. The drug was administered 45 minutes prior to induction of anesthesia intra-nasally. Following intra-nasal drug administration, anxiety was assessed at 0 minutes -baseline, 30 minutes, 45 minutes and at parental separation in the preoperative area just before shifting in operation theater using the mYPAS (modified Yale Preoperative Anxiety Scale). At induction, induction compliance was assessed using the induction compliance checklist and heamodynamic response to definitive airway was assessed.It was observed that intranasal dexmedetomidine in lower doses of 0.5 and 1µg/kg was effective in reducing anxiety from baseline values but was not sufficient for providing anxiolysis at the most stressful time - at parental separation and shifting to OR (Operating room). The dosage of 1.5µg/kg was found to be the most effective dose for allaying preoperative anxiety without any adverse effect. However, this dose was insufficient for optimizing induction as it is mainly anxiolytic and higher doses having additional sedative action may be required to make the child more compliant for induction of anesthesia.Based on our findings, we recommend that intranasal dexmedetomidine in the dose of 1.5µg/kg can be used for allaying preoperative anxiety, without any adverse events.• Question: To evaluate and compare the efficacy of three different doses of intranasal dexmedetomidine for premedication in children for preoperative anxiety using the mYPAS scale. • Findings: Dose of 1.5µg/kg can be used for allaying preoperative anxiety, without any adverse events. • Meaning: Optimum dose of intranasal dexmeditomedine which is efficient to allay preoperative anxiety in children.

Developing of SiO2 Nanoshells Loaded with Fluticasone Propionate for Potential Nasal Drug Delivery: Determination of Pro-Inflammatory Cytokines through mRNA Expression.

Mesoporous Silica Nanoparticles (MSN) are porous inorganic materials that have been extensively used for drug delivery due to their special qualities, such as biocompatibility, biodegradability, and non-toxicity. MSN is a promising drug delivery system to enhance the efficacy and safety of drug administration in nasal diseases like chronic rhinitis (CR). In this study, we used the sol-gel technique for MSN synthesis and incorporate fluticasone propionate (FP) for intranasal drug administration for the treatment of chronic rhinitis (CR). In order to confirm the particle size, shape, drug release, and compatibility, various instruments were used. MSN was effectively prepared with average sizes ranging between 400 ±&amp;nbsp;34&amp;nbsp;nm (mean ±&amp;nbsp;SD) as measured by dynamic light scattering (DLS), while zeta potential verified in all cases their positive charged surface. To investigate MSN features, the Fourier transform infrared spectrometer (FTIR), scanning electron microscopy (SEM), transmission electron microscope (TEM), thermal analysis, X-ray diffraction (XRD), and nitrogen adsorption/desorption measurement were used. The loaded compound was submitted to in vitro dissolution tests, and a remarkable dissolution rate improvement was observed compared to the crystalline drug in both pH conditions (1.2 and 7.4 pH). By using an MTT assay cell viability was assessed. The expression levels of the anti-inflammatory cytokines IL-4 and IL-5 were also measured using mRNA extraction from rat blood. Other characterizations like acute toxicity and hemolytic activity were also performed to confirm loaded MSN safety. Loaded MSN was incorporated in nasal spray prepared by using innovator excipients including poloxamer. After this, its nasal spray's physical characteristics were also determined and compared with a commercial product (Ticovate).

Formulation considerations for improving intranasal delivery of CNS acting therapeutics.

One of the principal impediments for the treatment of neurological conditions is the lack of ability of most of the medicinal agents to evade the blood-brain barrier. Among all the novel approaches to bypass the blood-brain barrier, nose to brain transport is the most patient compliant, non-invasive and effective approach. It directly transports drugs to the CNS via the trigeminal and olfactory nerves present in the nasal cavity. This review article focuses on anatomy and physiology of nasal cavity, potential of intranasal drug delivery, mechanisms of drug transport to brain, its advantages and limitations, novel intranasal formulations, marketed products, factors affecting nose to brain transport, formulation consideration of intranasal products and the future perspectives of CNS targeting via intranasal drug administration.