Nasal Application Research Articles

Methicillin-resistant Staphylococcus aureus mupirocin resistance rates in a large healthcare system

Methicillin-resistant Staphylococcus aureus (MRSA) is a common etiology of hospital-acquired infections (HAIs). One strategy to reduce HAIs due to MRSA involves a multistep decolonization process. This often involves nasal application of mupirocin 2% ointment. In our institution, when individuals meet criteria for decolonization, we recommend 5 days of treatment given twice daily. High levels of mupirocin resistance have been reported in some hospital systems, with >80% of tested isolates being resistant. To better understand our resistance levels, we selected 238 MRSA isolates from blood cultures to be tested for mupirocin resistance to correlate the presence of resistance and use of mupirocin for decolonization. We choose to assess MRSA blood isolates rather than nasal swabs given that we aim to prevent invasive MRSA infections, including blood stream infections, with decolonization. The blood cultures were collected from 11 acute-care facilities within our system from March 2021 through June 2022. High-level resistance was defined as an MIC >1,024 μg/mL according to Clinical and Laboratory Standards Institute guidelines. Of those, 7.14% showed high level resistance, and 76.47% occurred in those who were exposed to mupirocin and 23.53% occurred in those without mupirocin exposure (P = .0094). On average, those with high-level resistance had had more recent exposure to mupirocin compared to those without resistance, which was statistically significant. Also, those with high resistance, on average, received more doses of mupirocin, although this was not statistically significant. Conclusions: More recent and higher number of doses of mupirocin were associated with the development of resistance, which is consistent with what we know from pharmacodynamics of antibiotic resistance with other agents. These findings may be particularly important for those patients who have frequent hospitalizations and often require decolonization. Understanding baseline mupirocin resistance levels in an institution can assist with determining decolonization strategies.Disclosures: None

Brain insulin responsiveness is linked to age and peripheral insulin sensitivity.

Insulin action in the brain influences cognitive processes, peripheral metabolism and eating behaviour. However, the influence of age and peripheral insulin sensitivity on brain insulin action remains unclear. We used intranasal administration of insulin and functional magnetic resonance imaging in a randomized, placebo-controlled within-subject design in 110 participants (54 women, body mass index 18-49 kg/m2 , age 21-74 years). Cerebral blood flow was measured before and after nasal spray application to assess brain insulin action. Peripheral insulin sensitivity was assessed by a five-point oral glucose tolerance test. Linear regressions were used to investigate associations between age and peripheral insulin sensitivity with brain insulin action in predefined region of interests (i.e. insulin-sensitive brain regions). We found significant negative associations between age and insulin action in the hippocampus (β = -0.215; p = .017) and caudate nucleus (β = -0.184; p = .047); and between peripheral insulin sensitivity and insulin action in the amygdala (β = -0.190, p = .023). Insulin action in the insular cortex showed an interaction effect between age and peripheral insulin sensitivity (β = -0.219 p = .005). Furthermore, women showed the strongest negative association between age and hippocampal insulin action, while men showed the strongest associations with peripheral insulin sensitivity and age in reward-related brain regions. We could show a region-specific relationship between brain insulin responsiveness, age and peripheral insulin sensitivity. Our findings underline the need to study brain insulin action in both men and women and further substantiate that brain insulin sensitivity is a possible link between systemic metabolism and neurocognitive functions.

INFLUENCE OF PLASTIC SURGERY OF THE INFERIOR TURBINATE ON THE PATENCY OF THE EUSTACHIAN TUBE

Introduction: Chronic hypertrophic rhinitis is one of the most common diseases in rhinology. Various surgical techniques are used to reduce hypertrophic changes in the inferior turbinates. The aim of our study is to determine the impact of plastic surgery of the lower nasal turbinates, performed by cryoablation or radiocoblation, on the patency of the Eustachian tube and to determine how long the waiting period should be for activities that particularly require patent ear tubes, such as traveling by plane. Material: A total of 70 patients treated at the Department of Otolaryngology of the Military Institute of Aviation Medicine were qualified for the study. Due to the technique of conchoplasty of the lower nasal turbinates, the patients were divided into two groups. Group I consisted of 35 patients, including 15 women and 20 men, aged 24 to 62 (mean 42.67 years), operated on by cryoablation. Group II also comprised 35 patients, including 12 women and 23 men, aged 29 to 69 (mean 44.21 years), operated on by radiocoblation. Methods: Plastic surgeries of the lower nasal turbinates, also known as conchoplasties, were performed under local anesthesia with a cryosurgery machine with the use of a nasal applicator and an apparatus for submucosal coblation with the use of radio waves. The patency of the Eustachian tube was assessed by tympanometry before the operation and 1, 2 and 3 weeks after the operation. Results: No statistically significant (p < 0.001) disturbances of the patency of the Eustachian tubes were observed after conchoplastic surgeries, using both the cryoablation and radiocoablation methods. Conclusions: Conchoplasties of the lower nasal turbinates performed by cryo- and radiocoblation do not impair the patency of the Eustachian tubes. After operations on the lower nasal turbinates, the waiting period for activities that particularly require patent tubes should be two weeks.

3D Bioprinting in Otolaryngology: A Review.

The evolution of tissue engineering and 3D bioprinting has allowed for increased opportunities to generate musculoskeletal tissue grafts that can enhance functional and aesthetic outcomes in otolaryngology-head and neck surgery. Despite literature reporting successes in the fabrication of cartilage and bone scaffolds for applications in the head and neck, the full potential of this technology has yet to be realized. Otolaryngology as a field has always been at the forefront of new advancements and technology and is well poised to spearhead clinical application of these engineered tissues. In this review, current 3D bioprinting methods are described and an overview of potential cell types, bioinks, and bioactive factors available for musculoskeletal engineering using this technology is presented. The otologic, nasal, tracheal, and craniofacial bone applications of 3D bioprinting with a focus on engineered graft implantation in animal models to highlight the status of functional outcomes in vivo; a necessary step to future clinical translation are reviewed. Continued multidisciplinary efforts between material chemistry, biological sciences, and otolaryngologists will play a key role in the translation of engineered, 3D bioprinted constructs for head and neck surgery.

A PROSPECTIVE STUDY COMPARING THE OUTCOMES OF NASAL SEPTAL CLIP VERSUS MEROCEL APPLICATION AFTER NASAL SEPTAL CORRECTIVE SURGERY

Nasal splint application is an important step of septal corrective surgeries to keep the septum in midline after the surgery. Septal clip is most commonly used. In our study we have compared the use of nasal septal clip and Merocel application post surgery and the morbidities associated with it

Chitosan-Based Nanoparticles for Targeted Nasal Galantamine Delivery as a Promising Tool in Alzheimer's Disease Therapy.

Natural alkaloid galantamine is widely used for the treatment of mild to moderate Alzheimer's dementia. Galantamine hydrobromide (GH) is available as fast-release tablets, extended-release capsules, and oral solutions. However, its oral delivery can cause some unwanted side effects, such as gastrointestinal disturbances, nausea, and vomiting. Intranasal administration is one possible way to avoid such unwanted effects. In this work, chitosan-based nanoparticles (NPs) were studied as potential GH delivery vehicles for nasal application. The NPs were synthesized via ionic gelation and studied using dynamic light scattering (DLS) as well as by spectroscopic and thermal methods. The GH-loaded chitosan-alginate complex particles were also prepared as a way to modify the release of GH. The high loading efficiency of the GH was confirmed for both types of particles, at 67% for the GH-loaded chitosan NPs and 70% for the complex chitosan/alginate GH-loaded particles. The mean particle size of the GH-loaded chitosan NPs was about 240 nm, while the sodium alginate coated chitosan particles loaded with GH were expectedly bigger, with a mean particle size of ~286 nm. GH release profiles in PBS at 37 °C were obtained for both types of NPs, and it was found that the GH-loaded chitosan NPs allowed the prolonged release of the incorporated drug for a period of 8 h, while the complex GH-loaded chitosan/alginate NPs released the incorporated GH faster. The stability of the prepared GH-loaded NPs was also demonstrated after 1 year of storage at 5 °C ± 3 °C.

Safety Aspects and Rational Use of Testosterone Undecanoate in the Treatment of Testosterone Deficiency: Clinical Insights.

Testosterone deficiency is diagnosed by a serum total testosterone level below 300 ng/dL in combination with symptoms such as decreased energy and libido. These symptoms can be ameliorated by restoring serum testosterone to the physiologic range with testosterone therapy (TT). There are numerous forms of testosterone therapy, such as injectable, transdermal, nasal, and subcutaneous applications. There are also multiple formulations of injection, such as testosterone cypionate, testosterone enanthate, and testosterone undecanoate. Testosterone undecanoate (TU) is a long-acting ester formulation of testosterone that can be provided in an injectable or oral form. Oral testosterone undecanoate is marketed as Andriol, Jatenzo, Tlando, and Kyzatrex. Oral TU provides a convenient option for many patients, which may increase compliance with TT. Injectable testosterone undecanoate is marketed as Aveed and Nebido. Injectable TT remains the most cost-effective therapeutic option and is appropriate for most patients as an initial therapy. This review describes the pharmacokinetics of these testosterone undecanoate products and provides a guide for prescribers using these medications. While many forms of testosterone are appropriate for TT, a patient-centered discussion focused on goals of care should best guide physician prescription of these medications.

Lipid-based ayurvedic formulations of a single herb-Yashtimadhu (Glycyrrhiza glabra): Pharmaceutical standardization, shelf-life estimation and comparative characterization

BackgroundSingle herb Ayurvedic lipid-based formulations of Glycyrrhiza glabra are used as oral, nasal and topical applications for reducing radiotherapy induced side effects in oral cavity cancer patients. These formulations are reported to be de-glycyrrhized, thus minimizing adverse effects of glycyrrhizin on longer consumption. Being a proprietary formulation with specific ratio of herb, lipid and liquid media, there is a need of pharmaceutical standardization and stability study to be conducted for quality control and quality assurance. ObjectiveStandardization of Yashtimadhu Ghrut (YG) and Yashtimadhu Taila (YT) based on pharmaceutical characters, safety tests, chromatographic analysis and stability study. Material and methodsTwo formulations viz., YG and YT were prepared using cow's ghee and sesame oil, respectively. Basic physicochemical analysis, Thin Layer Chromatography, High Pressure Liquid Chromatography of glabridin and 18-β glycyrrhetinic acid, microbial load and heavy metal analysis were performed. Long term (0,3,6,9,12 months) as well as accelerated (0,3,6 months) stability study was conducted and extrapolated shelf-life was calculated for both the drugs. ResultOrganoleptic and basic physicochemical characters were comparable for both the products while safety parameters were within permissible limits. Extrapolated shelf-life was deduced as 1.74 and 0.67 years for YG and YT, respectively. ConclusionSingle herb- G. glabra based lipid formulations were standardized and monographs were established. Shelf-life, though complying with classical Ayurvedic texts, indicates further research work with respect to pre-treatment of lipids and packaging systems for its enhancement.

Effect of High-Flow Nasal Oxygenation on Gastric Insufflation in Patients Undergoing Laryngeal Microsurgery under Tubeless General Anesthesia with Neuromuscular Blockade

High-flow nasal oxygenation is an oxygen delivery method by which high concentrations of heated humidified oxygen are supplied via the nasal cavity. This study aimed to investigate the effect of high-flow nasal oxygenation on gastric volume change in adult patients undergoing laryngeal microsurgery under tubeless general anesthesia with neuromuscular blockade. Patients aged 19-80 years with an American Society of Anesthesiologists physical status 1 or 2 who were scheduled to undergo laryngoscopic surgery under general anesthesia were recruited. Patients received high-flow nasal oxygenation therapy at 70 L/min during surgery under general anesthesia with neuromuscular blockade. The cross-sectional area of the gastric antrum was measured via ultrasound in the right lateral position before and after high-flow nasal oxygenation, and the gastric volume was calculated. The duration of apnea, i.e., the duration of administration of high-flow nasal oxygenation in the paralyzed state, was also recorded. Of the 45 patients enrolled, 44 completed the study. There were no significant differences in the antral cross-sectional area in the right lateral position, gastric volume, and gastric volume per kg between before and after high-flow nasal oxygenation application. The median duration of apnea was 15 (interquartile range, 14-22) min. High-flow nasal oxygenation at 70 L/min during apnea with the mouth open did not influence the gastric volume in patients undergoing laryngeal microsurgery under tubeless general anesthesia with neuromuscular blockade.

Delivery of JAL-TA9 to the brain by nasal application

Delivery of JAL-TA9 to the brain by nasal application

Post-immunobiotics increase resistance to primary respiratory syncytial virus infection and secondary pneumococcal pneumonia.

Previously, we demonstrated that post-immunobiotics derived from Lactobacillus gasseri TMT36, TMT39, and TMT40 strains (HK36, HK39 and HK40, respectively) differentially regulated Toll-like receptor 3 (TLR3)-mediated antiviral respiratory immunity in infant mice. In this work, we investigated whether the HK36, HK39 and HK40 nasal treatments were able to improve the resistance against primary respiratory syncytial virus (RSV) infection and secondary pneumococcal pneumonia. Our results demonstrated that the three treatments increased the resistance to primary viral infection by reducing variations in body weight, RSV titers and lung damage of infected infant mice. Post-immunobiotics significantly enhanced the expressions of interferon (IFN)-λ, IFN-β, IFN-γ, interleukin(IL) - 1β, IL-6, IL-27, Mx1, RNAseL and 2'-5'-oligoadenylate synthetase 1 (OAS1) genes and decreased tumour necrosis factor (TNF)-α in alveolar macrophages of RSV-challenged mice. In addition, the studies in the model of RSV-Streptococcus pneumoniae superinfection showed that the HK39 and HK40 treatments were capable of reducing lung damage, lung bacterial cell counts, and the dissemination of S. pneumoniae into the blood of infant mice. The protective effect was associated with increases in IFN-β, IFN-γ, IL-10, and IL-27 in the respiratory tract. This study demonstrates that the nasal application of the post-immunobiotics HK39 and HK40 stimulates innate respiratory immunity and enhances the defences against primary RSV infection and secondary pneumococcal pneumonia offering an alternative to combat respiratory superinfections in children, which can be fatal.

1911. A Pilot Study to Evaluate the Effectiveness of Nasal and Oral Povidone Iodine in Reducing the Burden of Severe Acute Respiratory Syndrome 2 RNA in Patients with COVID-19

Abstract Background Nasal and oral application of topical antiseptics such as povidone iodine could potentially reduce the risk for transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, limited information is available on the efficacy of such agents in reducing the burden of SARS-CoV-2. Methods We conducted a pilot non-blinded, randomized trial to compare the effectiveness of 3 doses of povidone iodine (each dose with 10% intranasal and 1% gargle) administered every 8 hours versus the control with phosphate-buffered saline in reducing the burden of SARS-CoV-2 RNA in the nares and oropharynx of patients with COVID-19. Swabs were used to collect anterior nares and oropharynx samples before the first and second doses and 8 hours after the final dose (24 hours after the initial dose). Real-time polymerase-chain reaction (RT-PCR) was used to assess the burden of viral RNA. Analysis of variance was used to compare cycle threshold values for povidone iodine versus control patients. Subjects were surveyed about adverse reactions to treatment. Results As shown in the figure, SARS-CoV-2 cycle thresholds were similar in the povidone iodine (N=10 subjects) and control (N=8 subjects) groups prior to treatment. After initiation of treatment, there was no significant difference in cycle thresholds for the povidone iodine versus control subjects (P >0.05). No adverse effects of treatment were reported. Effect of intranasal and oral application of povidone iodine versus phosphate-buffered saline on nasal and oropharyngeal SARS-CoV-2 RNA. Error bars show standard error. Conclusion Our findings suggest that that nasal and oral application of povidone iodine have limited effectiveness in reducing the burden of SARS-CoV-2. Future studies are needed to assess for effectiveness of more frequent dosing intervals and to determine if povidone iodine reduces recovery of viable virus by culture. Disclosures All Authors: No reported disclosures.

Synthesis, characterization and evaluation of hyaluronic acid-based polymers for nasal delivery

Epidemiological research has found that between 5 and 12 percent of the population suffers from chronic rhinosinusitis. Patients are dealing with local side effects such as nasal dryness, sporadic sneezing, and nasal pain in addition to the inflammation. The aim of this study was to synthesize a polymer based on hyaluronic acid in order to provide lubrication combined with a ligand leading to a covalent binding on the nasal mucosa. Hyaluronic acid (HA) was modified with L-cysteine ethyl ester hydrochloride (CYS) via amid bond formation. Ellman's assay, together with spectroscopic techniques like IR and 1H NMR, confirmed that HACys had been successfully synthesized. It was demonstrated that HACys is safe for administration on the nasal mucosa. The mucoadhesive potential was determined by 3.26-fold with the rotating cylinder assay and 1.4-fold in terms of bioadhesive examination, respectively. Further, the stability of the modified polymer was improved by 7.6-fold compared to the unmodified polymer. Spraying the formulation on the nasal mucosa, the residence time of a model drug was 1.74-fold prolonged at the site of action compared to unmodified polymer. In light of these findings, modified hyaluronic acid (HACys) displayed compelling properties such as lubricity, targeted application, long-lasting effect, and safety and therefore could be an excellent candidate for nasal application.

Development of an intranasal formulation containing indomethacin and xylometazoline for rhinosinusitis treatment.

Use of the nasal route of drug administration dates back many years and is used both to achieve topical treatments and to allow systemic absorption. The objective was to develop a formulation with novel features which enhance prolonged contact with the nasal and sinusal lining, since this should increase any therapeutic benefit. The anti-inflammatory drug selected was indomethacin, which was combined with xylometazoline, an effective nasal decongestant agent. 28 Sprague-Dawley rats were used. They were then allocated at random to one of the four groups of equal size. All rats received a nasal application of 50mL of the platelet-activating factor solution at a concentration of 16 µg/mL and had induced rhinosinusitis. Indomethacin or xylometazoline HCl or both were dissolved in the oily phase of the solution and then a magnetic stirrer was used to homogenize the solution for 60 min at room temperature. All the O/W solutions exhibited stability and remained at neutral pH for the entire duration of the experiment. The only intervention was application of inactive 0.9% saline in group 1. The intervention was nasal application of xylometazoline and indomethacin in the combined formulation in group. The intervention was nasal application of xylometazoline only in group 3. The intervention was nasal application of indomethacin only in group 4. For the animals in group 1 (the controls), the mucosa had sustained a significant level of damage and the vessels were highly congested. Inflammatory cells were extensively infiltrating the mucosa. (Figure 1 - A1, 2, 3). In group 2, by contrast, the vessels were hardly congested and there were very few infiltrates. The epithelium appeared completely intact (Figure 1 - B1, 2, 3). Furthermore, when groups 1 and 2 were compared in terms of congested vessels, inflammatory cellular infiltrates and injury to the epithelium, the differences reached statistical significance, with p-values of <0.01, >0.001 and <0.001, respectively. Comparison of groups 2 and 4 with the control group also revealed statistically significant differences in terms of cellular infiltrates (p<0.001) and damage to the epithelium (p<0.001). For the degree of congestion of the vessels, however, the difference between groups was not at the level of statistical significance (p<0.071). Groups 3 and 4 differed at a statistically significant level in terms of degree of congested vessels, cellular infiltrates, and damage to the epithelium (p<0.025 and p<0.001). The sections from rats in groups 2 and 3 had a lower degree of congested vessels, which may be due to the actions of xylometazoline. In the future, topically applied intranasal NSAIDs will be valuable formulations. Innovative types of formulation, such as those demonstrating thixotropic behavior, permit the agent to remain in prolonged contact with the nasal and sinusal lining. Alongside increased efficacy, these preparations will also improve the side effect profile of NSAIDs, largely eliminating systemic effects.

An ambient-temperature stable nanoparticle-based vaccine for nasal application that confers long-lasting immunogenicity to carried antigens.

Polyhedrins are viral proteins present in a large family of baculoviruses that form occlusion bodies (polyhedra). These structures protect the virus particles from the outside environment until they are ingested by susceptible insects. Occluded viruses can sustain inclement weather for long periods of time. Therefore, the polyhedra is a natural preservative that keeps the viral structure intact at ambient temperature for years. In a previous study we identified the first 110 amino acids from polyhedrin (PH(1-110)) as a good candidate to carry antigens of interest. As a proof of concept, we produced a fusion protein with PH(1-110) and the green fluorescent protein (PH(1-110)GFP). The fusion protein associates spontaneously during its synthesis resulting in the formation of nanoparticles. Nasal immunization with these nanoparticles and in the absence of any adjuvant, results in a robust immune response with the production of IgG immunoglobulins that remained elevated for months and that selectively recognize the GFP but not PH(1-110). These results indicate that PH(1-110) is poorly immunogenic but capable of enhancing the immune response to GFP.

Development of In Vitro Evaluation System for Assessing Drug Dissolution Considering Physiological Environment in Nasal Cavity.

Estimating the dissolution behavior of a solid in the nasal mucus is challenging for solid dosage forms designed for the nasal application as the solid dissolves into nasal mucus and permeates through the mucosa. In the current study, the dissolution behavior of powders in the artificial nasal fluid was investigated using a 3D-printed chamber system to establish in vitro evaluation system for the dissolution of solid formulations that can simulate the intranasal environment in vivo. The dissolution rates of the five model drugs correlated with their solubility (r2 = 0.956, p &lt; 0.01). The permeation rate of drugs across the Calu-3 cell layers after powder application depends on the membrane permeability of the drug. An analysis of membrane permeability considering the dissolution of powders showed the possibility of characterizing whether the drug in the powder was dissolution-limited or permeation-limited. This suggests that critical information can be obtained to understand which mechanism is more effective for the improvement of drug absorption from powders. This study indicates that the elucidation of drug dissolution behavior into nasal mucus is an important factor for the formulation of nasal powders and that the in vitro system developed could be a useful tool.

Coste-efectividad de la oxigenoterapia de alto flujo en el tratamiento de la neumonía por SARS-CoV-2

Introductionhigh-oxygen nasal cannulas in patients with respiratory failure secondary to SARS-CoV-2 pneumonia have not been studied from a cost-effectiveness point of view. MethodsRetrospective analysis of patients who had entered the COVID-area of an intensive medicine service in a third reference hospital, between March-December 2020. An effectiveness cost analysis was carried out comparing 2therapeutic decisions: the experimental strategy was defined as a mixed strategy consisting of the initial application of high flow nasal oxygen (HFNO) and application of VMI only to HFNO failures. The optimal rational decision was defined as maximizing expected profit, and economic efficiency was assessed by calculating the Incremental Cost-Effectiveness Ratio (ICER) for years of life gained. ResultsOf the 185 patients tested, 101 (55%) received invasive mechanical ventilation immediately and 84 (45%) were treated with HFNO at the outset. In the cost-effectiveness analysis, comparing both therapeutic strategies, the probability that the experimental strategy would be more effective was 0.974, reaching statistical significance: Difference in average proportions -0.113; 95% CI:-0.018 to -0.208. This corresponds to an NNT of 9 patients. The optimal decision was HFNO's strategy followed by VMI in HFNO failures. This option had an RCEI of 5582 euros per year of life gained. ConclusionsIt is important to establish in the future reliable markers in the use of HFNO so that this therapy improves its cost-effective benefits.

A REVIEW ON CHALLENGES IN DEVELOPING NASAL SPRAYS

The aim of this review is to provide information regarding significant aspects and challenges in developing of nasal sprays. This article outlined the relevant aspects of nasal anatomy, physiology &amp; biological, physicochemical and pharmaceutical factors that must be considered during formulation development of nasal sprays. Nasal drug delivery system is the most preferable route than other routes of administration as it gives rapid onset of action. It is considered as a convenient and reliable route for local and also for systemic administration of drugs. The main highlights of this review includes types, advantages, disadvantages, mechanisms of drug absorption, factors of nasal drug absorption, formulation, methods of manufacturing and filling of nasal sprays, evaluation, characterization and applications.

Preparation and detailed characterization of the thiomer chitosan–cysteine as a suitable mucoadhesive excipient for nasal powders

The therapeutic application of nasal powders requires the development of novel mucoadhesive excipients. Thiolated polymers exhibit significant potential for this purpose based on their increased mucoadhesion attributable to the formation of disulfide bonds between the polymer and mucus surface. A chitosan–cysteine (chit-cyst) conjugate was synthesized using 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide in aqueous solution. The synthetic yield and synthesis conditions were optimized, and the efficiency of the reaction was evaluated. Rheological measurements revealed that the polymer derivative exhibited increased mucoadhesive properties in comparison to chitosan powder. To characterize the polymer, a novel purity investigation method was developed and verified to investigate the residual l-cysteine content. The results revealed that l-cysteine was not detectable in the resultant polymer matrix. Based on the cytotoxicity studies, chit-cyst was found to be safe for nasal application. Thereafter, nasal powder formulations were prepared using the polymer and the antiparkinsonian drug levodopa methyl ester hydrochloride by freeze-drying to investigate their nasal applicability. Based on the in vitro studies, these powders might be suitable for reducing the off periods of Parkinson’s disease because of their expected higher in vivo mucoadhesion.

Intranasal delivery: An attractive route for the administration of nucleic acid based therapeutics for CNS disorders.

The etiologies of several cardiovascular, inflammatory, neurological, hereditary disorders, cancer, and infectious diseases have implicated changes in the genetic set up or genetic mutations as the root cause. Nucleic acid based therapeutics (NBTs) is a new class of biologics that are known to regulate gene expression at the transcriptional and post-transcriptional level. The NBTs include oligonucleotides, nucleosides, antisense RNA, small interfering RNAs, micro RNA etc. In recent times, this new category of biologics has found enormous potential in the management of cardiovascular, inflammatory, neurological disorders, cancer, infectious diseases and organ transplantation. However, the delivery of NBTs is highly challenging in terms of target specificity (intracellular delivery), mononuclear phagocyte system uptake, stability and biodistribution. Additionally, management of the above mentioned disorders require regular and intrusive therapy making non-invasive routes preferable in comparison to invasive routes like parenteral. The nasal route is garnering focus in delivery of NBTs to the brain in the management of several CNS disorders due to the associated merits such as non-invasiveness, possibility of chronic delivery, improved patient compliance, avoidance of hepatic and gastrointestinal metabolism as well as ability to bypass the BBB. Hence in recent times, this route has been sought by the reserachers as an alternative to parenteral therapy for the delivery of several NBTs. This review shall focus on an array of NBTs delivered through nasal route, their challenges, applications and opportunities. The novel delivery systems for incorporating NBTs; their targeting strategies shall be critically reviewed. The challenges towards regulatory approvals and commercialization shall also be discussed at large. Comparison of learnings derived from the success and barriers in nasal delivery of NBTs will help in identification of futuristic opportunities for their translation from bench to bedside.