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Fulltext Scoring System for Lesions Induced by Different Strains of Newcastle Disease Virus in Chicken

Hussein EA, Hair-Bejo M, Adamu L, Omar AR, Arshad SS, Awad EA, et al.

Vet Med Int, 2018;2018:9296520.
PMID: 30631413 DOI: 10.1155/2018/9296520

Newcastle disease virus strains are velogenic, mesogenic, and lentogenic. This study aims to design a scoring system for lesions induced by different strains of Newcastle disease virus in chicken. Three experiments were conducted. In experiments 1 and 2, chickens were divided into infected and control groups. Infected groups of experiments 1 and 2 consisted of 6 and 24 specific pathogen-free (SPF) chickens, respectively. Control groups in experiments 1 and 2 consisted of 6 and 15 SPF chickens, respectively. In infected groups, infection was induced by intranasal administration of 105 50% EID50/0.1 mL of velogenic Newcastle disease virus strain (vNDV). Infected chickens in experiment 1 were euthanised by cervical dislocation on days 3, 6, and 7 postinoculation (pi). Infected chickens in experiment 2 were euthanised at hours (hrs) 2, 4, 6, 12 and days 1, 2, 4, and 6 pi. Chickens of the control group in experiment 1 were euthanised on days 3 and 7 pi, whereas control group chickens in experiment 2 were euthanised on days 0, 1, 2, 4, and 6 pi. Then in experiment 3, 15 SPF chickens were divided into three groups; in the first group, 5 SPF chickens were infected with vNDV, in the second group, 5 SPF chickens were infected with lentogenic NDV (lNDV) (103.0 EID50/0.1 mL), and the third group was kept without infection as a control group. Chickens were euthanised on day 5 pi. In all previous experiments, tissues of brain, trachea, lung, caecal tonsil, liver, kidney, spleen, heart, proventriculus, intestine, and thymus were collected, fixed in 10% buffered formalin, embedded in paraffin, and sectioned. HS staining was applied. Tissues were examined under light microscope and changes were recorded. A scoring system was designed for lesions induced by different strains of NDV and, accordingly, lesions were scored. The scoring system was found helpful in the evaluation of disease severity.

Matched MeSH terms: Administration, Intranasal
Enhanced nose-to-brain delivery of tranilast using liquid crystal formulations

See GL, Arce F, Dahlizar S, Okada A, Fadli MFBM, Hijikuro I, et al.

J Control Release, 2020 Sep 10;325:1-9.
PMID: 32598958 DOI: 10.1016/j.jconrel.2020.06.028

Intranasal administration is poised as a competent method in delivering drugs to the brain, because the nasal route has a direct link with the central nervous system bypassing the formidable blood-brain barrier. C17-monoglycerol ester (MGE) and glyceryl monooleate (GMO) as liquid crystal (LC)-forming lipids possess desirable formulation characteristics as drug carriers for intranasally administered drugs. This study investigated the effect of LC formulations on the pharmacokinetics of tranilast (TL), a lipophilic model drug, and its distribution in the therapeutic target regions of the brain in rats. The anatomical biodistribution of LC formulations was monitored using micro-computed tomography tandem in vivo imaging systems. MGE and GMO effectively formed LC with suitable particle size, zeta potential, and viscosity supporting the delivery of TL to the brain. MGE and GMO LC formulations enhanced brain uptake by 10- to 12-fold and 2- to 2.4- fold, respectively, compared with TL solution. The olfactory bulb had the highest TL concentration and fluorescent signals among all the brain regions, indicating a direct nose-to-brain delivery pathway of LC formulations. LC-forming lipids, MGE and GMO, are potential biomaterials in formulations intended for intranasal administration.

Matched MeSH terms: Administration, Intranasal
Fulltext Mometasone furoate intranasal spray is effective in reducing symptoms and adenoid size in children and adolescents with adenoid hypertrophy

Ghafar MHA, Mohamed H, Mohammad NMY, Mohammad ZW, Madiadipoera T, Wang Y, et al.

Acta Otorrinolaringol Esp (Engl Ed), 2019 08 07;71(3):147-153.
PMID: 31400807 DOI: 10.1016/j.otorri.2019.04.004

INTRODUCTION: The use of mometasone furoate (MF) intranasal spray in treating adenoid hypertrophy (AH) has a variable outcome due the different methods of adenoid size evaluation. The aim of our study was to evaluate the effect of MF intranasal spray in children and adolescents with AH using a reliable and consistent endoscopic evaluation.
MATERIAL AND METHOD: A prospective interventional study was conducted. Evaluation took place during the first visit (week 0) and second visit (week 12). Symptoms of nasal obstruction, rhinorrhoea, cough and snoring were assessed, and an overall total symptoms score was obtained. A rigid nasoendoscopic examination using a four-grading system of adenoid size from 1 to 4 was performed. Patients were treated with MF intranasal spray for 12 weeks. Patients' aged 7-11-years old used 1 spray in each nostril once daily, while patients aged 12-17 used two sprays in each nostril once daily. Reassessment was carried out during the second visit (week 12).
RESULTS: A total of 74 patients was recruited. There were significant improvements from week 0 to week 12 in the symptoms' score for nose obstruction, rhinorrhoea, cough, snoring including the total nasal symptoms' score (p<0.001). AH significantly reduced in size from week 0 (2.89±.87) to week 12 (1.88±.83) (p<0.001).
CONCLUSION: MF intranasal spray is effective in improving the symptoms attributed to AH as well as reducing the adenoid size. MF intranasal spray is advocated as a treatment option before adenoidectomy is considered.

Matched MeSH terms: Administration, Intranasal
Nanoparticles Based Intranasal Delivery of Drug to Treat Alzheimer's Disease: A Recent Update

Pandey M, Choudhury H, Verma RK, Chawla V, Bhattamisra SK, Gorain B, et al.

CNS Neurol Disord Drug Targets, 2020;19(9):648-662.
PMID: 32819251 DOI: 10.2174/1871527319999200819095620

Alzheimer Association Report (2019) stated that the 6th primary cause of death in the USA is Alzheimer's Disease (AD), which leads to behaviour and cognitive impairment. Nearly 5.8 million peoples of all ages in the USA have suffered from this disease, including 5.6 million elderly populations. The statistics of the progression of this disease is similar to the global scenario. Still, the treatment of AD is limited to a few conventional oral drugs, which often fail to deliver an adequate amount of the drug in the brain. The reduction in the therapeutic efficacy of an anti-AD drug is due to poor solubility, existence to the blood-brain barrier and low permeability. In this context, nasal drug delivery emerges as a promising route for the delivery of large and small molecular drugs for the treatment of AD. This promising pathway delivers the drug directly into the brain via an olfactory route, which leads to the low systemic side effect, enhanced bioavailability, and higher therapeutic efficacy. However, few setbacks, such as mucociliary clearance and poor drug mucosal permeation, limit its translation from the laboratory to the clinic. The above stated limitation could be overcome by the adaption of nanoparticle as a drug delivery carrier, which may lead to prolong delivery of drugs with better permeability and high efficacy. This review highlights the latest work on the development of promising Nanoparticles (NPs) via the intranasal route for the treatment of AD. Additionally, the current update in this article will draw the attention of the researcher working on these fields and facing challenges in practical applicability.

Matched MeSH terms: Administration, Intranasal
Efficacy of intranasal administration of formalin-killed Pasteurella haemolytica A2 against intratracheal challenge in goats

Effendy AW, Zamri-Saad M, Puspa R, Rosiah S

Vet Rec, 1998 Apr 18;142(16):428-31.
PMID: 9595632

A trial was conducted to compare the efficacy of intranasal vaccination in protecting goats against pneumonic pasteurellosis with intramuscular vaccination using an oil adjuvant vaccine, and a combination of the two methods. Forty goats were divided into four equal groups. Group 1 was vaccinated twice intranasally with formalin-killed Pasteurella haemolytica A2, group 2 was vaccinated twice intramuscularly with an oil adjuvant vaccine containing P haemolytica A7, and group 3 was initially vaccinated intranasally with the formalin-killed P haemolytica A2 followed by intramuscular vaccination with the oil adjuvant vaccine. In each group the two vaccinations were carried out four weeks apart. Group 4 was the unvaccinated control group. All goats were challenged intratracheally with 4 ml of an inoculum containing live P haemolytica A2 at a concentration of 1.3 x 10(7) colony forming units/ml two weeks after the last vaccination and were killed 14 days after the challenge. Although group 2 showed the highest clinical score following the challenge, deaths were observed only in group 3. Three goats in group 1 had pneumonic lung lesions, compared with six goats in group 2 and all the goats in groups 3 and 4. The lung lesions in group 1 were significantly (P < 0.05) less severe than in groups 3 and 4. Similarly, the lesions in group 2 were markedly less severe than in groups 3 and 4, although the differences were not significant. The difference between the extent of the lung lesions in the goats in groups 1 and 2 was not significant. Antibody against P haemolytica A2 in group 1 reached peak levels and was significantly (P < 0.01) higher than in the control group one week after the second vaccination, before declining.

Matched MeSH terms: Administration, Intranasal
Fulltext Intranasal administration of Lignosus rhinocerotis (Cooke) Ryvarden (Tiger Milk mushroom) extract attenuates airway inflammation in murine model of allergic asthma

Muhamad SA, Muhammad NS, Ismail NDA, Mohamud R, Safuan S, Nurul AA

Exp Ther Med, 2019 May;17(5):3867-3876.
PMID: 30988772 DOI: 10.3892/etm.2019.7416

Asthma is a chronic inflammatory disorder in the airways that involves the activation of cells and mediators. Lignosus rhinocerotis (Cooke) Ryvardan or Tiger Milk mushroom is a medicinal mushroom that is traditionally used to treat inflammatory diseases including asthma. In this study, the protective effects of intranasal administration of L. rhinocerotis extract (LRE) in ovalbumin (OVA)-induced airway inflammation mouse model were investigated. Mice were sensitized by intraperitoneal (i.p) injection on days 0 and 14, followed by a daily challenge with 1% OVA from days 21 to 27. Following OVA challenge, LRE and dexamethasone were administered via intranasal and i.p. injection respectively. On day 28, the level of serum immunoglobulin (Ig)E, differential cell counts and T-helper (Th) 2 cytokines in bronchoalveolar lavage fluid (BALF) fluid, cell subset population in lung-draining lymph nodes (LNs), leukocytes infiltration and mucus production in the lungs of the animals was measured. Results demonstrated that intranasal administration of LRE significantly suppressed the level of inflammatory cell counts in BALF as well as populations of CD4+ T-cells in lung draining LNs. Apart from that, LRE also significantly reduced the level of Th2 cytokines in BALF and IgE in the serum in OVA-induced asthma. Histological analysis also demonstrated the amelioration of leukocytes infiltration and mucus production in the lungs. Overall, these findings demonstrated the attenuation of airway inflammation in the LRE-treated mice therefore suggesting a promising alternative for the management of allergic airway inflammation.

Matched MeSH terms: Administration, Intranasal
The effect of Pasteurella haemolytica A2 infection on phagocytosis efficiency of caprine broncho-alveolar macrophages

Zamri-Saad M, Mera HR

J. Vet. Med. B Infect. Dis. Vet. Public Health, 2001 Sep;48(7):513-8.
PMID: 11666033

An experiment was designed to study the in vivo effect of Pasteurella haemolytica A2 infection on the phagocytosis activity of caprine broncho-alveolar macrophages and the extent of pneumonic lesions. Twelve healthy local Kacang goats, about 7 months of age, were divided into two groups of six. Goats in group 1 were inoculated intratracheally with 4 ml inoculum containing 2.8 x 10(9) colony-forming units (CFU)/ml of Staphylococcus aureus. Goats in group 2 were inoculated intratracheally with 4 ml of inoculum containing 9.5 x 10(8) CFU/ml of Pasteurella haemolytica A2 isolated earlier from pneumonic lungs of goat. At intervals of 3 and 7 days post-challenge five goats from each group were killed and the lungs were washed with sterile phosphate-buffered saline. Smears were prepared from the lung washing fluid and the number of macrophages with phagocytic activity was determined. At day 3 post-infection, goats of both groups showed a similar pattern of pneumonic lesion. The lung washing fluid of goats in group 2 was found to contain numerous neutrophils and macrophages. Goats in group 2 showed significantly (P < 0.05) higher extent of lung lesions than group 1. Similarly, the average extent of lung lesions was significantly (P < 0.05) more severe in group 2 at day 7 post-infection. The lung washing fluid contained mostly macrophages. The phagocytic activity following S. aureus infection was more efficient and significantly (P < 0.01) higher compared with infection by P. haemolytica A2. There were weak correlations between the extent of pneumonic lesion and the phagocytic activity. Thus, goats with poor phagocytic activity were likely to develop more extensive lung lesions.

Matched MeSH terms: Administration, Intranasal
Interlink Between Insulin Resistance and Neurodegeneration with an Update on Current Therapeutic Approaches

Bhattamisra SK, Shin LY, Saad HIBM, Rao V, Candasamy M, Pandey M, et al.

CNS Neurol Disord Drug Targets, 2020;19(3):174-183.
PMID: 32418534 DOI: 10.2174/1871527319666200518102130

The interlink between diabetes mellitus and neurodegenerative diseases such as Alzheimer's Disease (AD) and Parkinson's Disease (PD) has been identified by several researchers. Patients with Type-2 Diabetes Mellitus (T2DM) are found to be affected with cognitive impairments leading to learning and memory deficit, while patients with Type-1 Diabetes Mellitus (T1DM) showed less severe levels of these impairments in the brain. This review aimed to discuss the connection between insulin with the pathophysiology of neurodegenerative diseases (AD and PD) and the current therapeutic approached mediated through insulin for management of neurodegenerative diseases. An extensive literature search was conducted using keywords "insulin"; "insulin resistance"; "Alzheimer's disease"; "Parkinson's disease" in public domains of Google scholar, PubMed, and ScienceDirect. Selected articles were used to construct this review. Studies have shown that impaired insulin signaling contributes to the accumulation of amyloid-β, neurofibrillary tangles, tau proteins and α-synuclein in the brain. Whereas, improvement in insulin signaling slows down the progression of cognitive decline. Various therapeutic approaches for altering the insulin function in the brain have been researched. Besides intranasal insulin, other therapeutics like PPAR-γ agonists, neurotrophins, stem cell therapy and insulin-like growth factor-1 are under investigation. Research has shown that insulin insensitivity in T2DM leads to neurodegeneration through mechanisms involving a variety of extracellular, membrane receptor, and intracellular signaling pathway disruptions. Some therapeutics, such as intranasal administration of insulin and neuroactive substances have shown promise but face problems related to genetic background, accessibility to the brain, and invasiveness of the procedures.

Matched MeSH terms: Administration, Intranasal
The influence of intranasal peste des petits ruminants (PPR) vaccine administration alone or with phytogenic mucoadhesive delivery system on PPR outbreak outcomes in goats

Ezeasor CK, Emikpe BO, Shoyinka SV, Sabri MY

J Immunoassay Immunochem, 2021 Jul 04;42(4):424-443.
PMID: 33724901 DOI: 10.1080/15321819.2021.1895216

This study reports the influence of peste des petits ruminants (PPR) vaccination on the clinico-pathological outcomes of PPR in the face of an outbreak. Twenty-two West African dwarf goats procured for a different study started showing early signs of PPR during acclimatization. In response, PPR vaccine was administered either intranasally with phytogenic mucoadhesive gum (Group A; n = 6) or without gum (Group B; n = 6); subcutaneously (Group C; n = 6) or not vaccinated (Group D; n = 4) and studied for 21 days. The clinical scores, hematology, serology and pathology scores were evaluated. Clinical signs of PPR were present in all groups, presenting a percentage mortality of 33%; 33%; 64% and 100% for Groups A, B, C, and D, respectively. Polycythemia and mild leukopenia were observed in all groups, and all animals were seropositive by day 7 post-vaccination. The lung consolidation scores were low in Groups A and B, compared to Group C. Histopathological lesions consistent with PPR was observed in the lymphoid organs, gastrointestinal tract, and lungs with the presence of PPR antigen as detected by immunohistochemistry. The findings suggest that intranasal vaccination with or without mucoadhesive gum may influence the outcome of PPR infection more than the subcutaneous route in the face of an outbreak.

Matched MeSH terms: Administration, Intranasal
Lipid-based pulmonary delivery system: a review and future considerations of formulation strategies and limitations

Ngan CL, Asmawi AA

Drug Deliv Transl Res, 2018 10;8(5):1527-1544.
PMID: 29881970 DOI: 10.1007/s13346-018-0550-4

Inhalation therapy of lipid-based carriers has great potential in direct target towards the root of respiratory diseases, which make them superior over other drug deliveries. With the successful entry of lipid carriers into the target cells, drugs can be absorbed in a sustained release manner and yield extended medicinal effects. Nevertheless, translation of inhalation therapy from laboratory to clinic especially in drug delivery remains a key challenge to the formulators. An ideal drug vehicle should safeguard the drugs from any premature elimination, facilitate cellular uptake, and promote maximum drug absorption with negligible toxicity. Despite knowing that lung treatment can be done via systemic delivery, pulmonary administration is capable of enhancing drug retention within the lungs, while minimizing systemic toxicity with local targeting. Current inhalation therapy of lipid-based carriers can be administered either intratracheally or intranasally to reach deep lung. However, the complex dimensions of lung architectural and natural defense mechanism poise major barriers towards targeted pulmonary delivery. Delivery systems have to be engineered in a way to tackle various diseases according to their biological conditions. This review highlights on the developmental considerations of lipid-based delivery systems cater for the pulmonary intervention of different lung illnesses.

Matched MeSH terms: Administration, Intranasal
Comparative evaluation of the degree of pegylation of poly(lactic-co-glycolic acid) nanoparticles in enhancing central nervous system delivery of loperamide

Kirby BP, Pabari R, Chen CN, Al Baharna M, Walsh J, Ramtoola Z

J Pharm Pharmacol, 2013 Oct;65(10):1473-81.
PMID: 24028614 DOI: 10.1111/jphp.12125

In this study, we examined the relative cellular uptake of nanoparticles (NPs) formulated using poly(lactic-co-glycolic acid) (PLGA) polymers with increasing degree of pegylation (PLGA-PEG) and their potential to deliver loperamide to the brain of a mouse.

Matched MeSH terms: Administration, Intranasal
The effects of dexamethasone on the response of bronchus-associated lymphoid tissue to intranasal administration of formalin-killed Pasteurella haemolytica A2 in goats

Zamri-Saad M, Effendy AW

Vet Res Commun, 1999 Dec;23(8):467-73.
PMID: 10672963

A trial was conducted to observe the immediate and chronic effects in goats of dexamethasone administration on the bronchus-associated lymphoid tissue (BALT) response to intranasal administration of formalin-killed Pasteurella haemolytica A2. Twenty-four goats were divided into four groups. Those in group 1 were injected intramuscularly with 1 mg/kg dexamethasone on three consecutive days, followed by intranasal exposure to formalin-killed P. haemolytica A2 one day after the last dexamethasone treatment. The goats in group 2 were similarly injected with dexamethasone followed by intranasal exposure to formalin-killed P. haemolytica A2 21 days after the last dexamethasone treatment. The animals in group 3 were exposed intranasally to formalin-killed P. haemolytica A2 without prior dexamethasone treatment. The animals in group 4 were untreated controls. The intranasal exposures to formalin-killed P. haemolytica A2 were repeated 2 weeks later. Intranasal exposure to formalin-killed P. haemolytica 1 day after dexamethasone treatment further reduced the number and size of BALT compared to the untreated control. Significantly (p < 0.01) more reduction of BALT occurred in goats exposed to formalin-killed P. haemolytica A2 21 days after dexamethasone treatment. On the other hand, intranasal exposure of goats without prior dexamethasone treatment stimulated the BALT compared to the untreated controls.

Matched MeSH terms: Administration, Intranasal
Stimulation of the bronchus-associated lymphoid tissue of goats and its effect on in vitro colonization by Pasteurella haemolytica

Effendy AW, Zamri-Saad M, Maswati MA, Ismail MS, Jamil SM

Vet Res Commun, 1998 Apr;22(3):147-53.
PMID: 9618886

Twenty goats of about 7 months of age were divided into five groups. The goats in groups 1 and 2 were exposed once, using an intranasal spray to 2 ml of an inoculum containing 10(6) colony-forming units/ml of living or dead Pasteurella haemolytica A2, respectively. The goats in groups 3 and 4 were similarly exposed twice at a 2-week interval. Group 5 was the untreated control. The number and size of the bronchus-associated lymphoid tissue (BALT) in goats exposed twice to either living or dead organisms were significantly (p < 0.05) increased compared with those exposed once and with the unexposed control. In vitro colonization by living P. haemolytica A2 onto the lung tissue in which the BALT had been stimulated by two exposures of either living or dead organisms was significantly (p < 0.05) reduced. The study indicates that stimulation of the respiratory mucosal immunity may prevent P. haemolytica A2 infection.

Matched MeSH terms: Administration, Intranasal
Influenza vaccine concurrently administered with a combination measles, mumps, and rubella vaccine to young children

Lum LC, Borja-Tabora CF, Breiman RF, Vesikari T, Sablan BP, Chay OM, et al.

Vaccine, 2010 Feb 10;28(6):1566-74.
PMID: 20003918 DOI: 10.1016/j.vaccine.2009.11.054

Children aged 11 to <24 months received 2 intranasal doses of live attenuated influenza vaccine (LAIV) or placebo, 35+/-7 days apart. Dose 1 was administered concomitantly with a combined measles, mumps, and rubella vaccine (Priorix). Seroresponses to measles and mumps were similar between groups. Compared with placebo, response rates to rubella in LAIV+Priorix recipients were statistically lower at a 15 IU/mL threshold (83.9% vs 78.0%) and the prespecified noninferiority criteria were not met. In a post hoc analysis using an alternate widely accepted threshold of 10 IU/mL, the noninferiority criteria were met (93.4% vs 89.8%). Concomitant administration with Priorix did not affect the overall influenza protection rate of LAIV (78.4% and 63.8% against antigenically similar influenza strains and any strain, respectively).

Matched MeSH terms: Administration, Intranasal
Protective effect following intranasal exposure of goats to live Pasteurella multocida B:2

Zamri-Saad M, Ernie ZA, Sabri MY

Trop Anim Health Prod, 2006 Oct-Nov;38(7-8):541-6.
PMID: 17265769

This study aimed to determine the effect of intranasal exposure to low doses of Pasteurella multocida B:2 on survival of goats challenged with high doses of the same organism. Eighteen goats were selected and divided into three groups. Goats of group 1 were exposed intranasally twice, with a two-week interval, to 7 x 10(6) cfu/ml of live P. multocida B:2. Goats of group 2 were not exposed to P. multocida B:2 but were kept together with the exposed group 1. Goats of group 3 remained as unexposed controls and were kept separated from the other two groups. Serum samples were collected at weekly intervals to determine the antibody levels. At week 5 post exposure, all goats were challenged subcutaneously with 3.7 x 10(10) cfu/ml of live P. multocida B:2. Following challenge exposure, 8 (67%) goats (4 goats from each of groups 1 and 2) were killed owing to haemorrhagic septicaemia. Four goats were killed peracutely within 48 h post challenge, while the other four goats were killed acutely between 2 and 4 days post challenge. None of the goats of group 3 were killed for haemorrhagic septicaemia. Goats of groups 1 and 2 showed significantly (p < 0.05) higher antibody levels following the first intranasal exposure to P. multocida B:2. However, only group 1 retained the significantly (p < 0.05) high antibody levels following a second intranasal exposure, and remained significantly (p < 0.05) higher than groups 2 and 3 at the time of challenge. P. multocida B:2 was successfully isolated from various organs of goats that were killed between 1 and 4 days post challenge.

Matched MeSH terms: Administration, Intranasal
Cellular and humoral responses in the respiratory tract of goats following intranasal stimulation using formalin-killed Pasteurella haemolytica A2

Zamri-Saad M, Effendy AW, Israf DA, Azmi ML

Vet Microbiol, 1999 Mar 12;65(3):233-40.
PMID: 10189198

A study to determine the immunoglobulin and cellular responses in the respiratory tract of goats following intranasal exposures to formalin-killed Pasteurella haemolytica A2 was carried out. Forty-two goats were divided into two groups. Goats in Group 1 were subjected to double intranasal exposures to formalin-killed P. haemolytica A2 while goats in Group 2 were the unexposed control. Prior to and at weekly intervals post-exposure, three goats from each group were killed, serum samples were collected while the lungs were flushed with 50 ml normal saline before the right apical lobes were fixed in 10% buffered formalin. Both serum and lung lavage fluid were subjected to enzyme-linked immunosorbent assay (ELISA) to determine the levels of IgA, IgM and IgG while the formalin-fixed tissues were examined histologically. IgA levels in the lung lavage fluid increased rapidly to reach a significantly (p < 0.05) high level as early as Week 2 post-exposure and remained significantly (p < 0.05) high throughout the study period. The IgM levels increased at an intermediate rate to reach a significantly (p < 0.05) high level at Week 3 post-exposure before they decreased to an insignificant (p > 0.05) level the following week and the weeks thereafter. IgG levels increased gradually and only reached a significantly (p < 0.01) high level at Weeks 5 and 6 of the study. The size of the bronchus-associated lymphoid tissue (BALT) and the number of lymphocytes in BALT increased significantly from Week 2 and remained high thereafter. However, differences in the numbers of BALT were insignificant (p > 0.05) initially before becoming significantly (p < 0.05) high at Weeks 5 and 6. The BALT responses were parallel to those of imunoglobulins in the lung lavage fluid.

Matched MeSH terms: Administration, Intranasal
Nose-to-brain delivery of teriflunomide-loaded lipid-based carbopol-gellan gum nanogel for glioma: Pharmacological and in vitro cytotoxicity studies

Gadhave D, Rasal N, Sonawane R, Sekar M, Kokare C

Int J Biol Macromol, 2021 Jan 15;167:906-920.
PMID: 33186648 DOI: 10.1016/j.ijbiomac.2020.11.047

The research work was intended to formulate teriflunomide (TFM) loaded nano lipid-based (TNLC) carbopol-gellan gum in situ gel (TNLCGHG) and to investigate its therapeutic efficacy against glioma, a brain and spine tumor. Nanoformulation was developed using gellan gum and carbopol 974P as gelling and mucoadhesive agents, respectively, Glyceryl di-behenate and Glyceryl mono-linoleate blend as lipids, and Gelucire 44/14: water blend as surfactant system. Globule size, PDI, zeta potential, encapsulation efficiency, mucoadhesive strength, and nasal permeation were found to be 117.80 nm, 0.56, -21.86 mV, 81.16%, 4.80 g, and 904 μg/cm2, respectively. Anticancer efficacy of TFM-loaded nano lipid-based carbopol-gellan gum in situ gel (TNLCGHG) was determined in human U-87MG glioma cell line. IC50 was found 7.0 μg/mL for TNLCGHG, 4.8 μg/mL for pure TFM, and 78.5 μg/mL for TNLC, which approve the superiority of surfactant along with gellan gum as permeation enhancer. Brain Cmax for technetium (99mTC) labeled intranasal (i.n.) 99mTC-TNLCGHG was found 2-folds higher than 99mTC-TNLC (i.n.) and 99mTC-TNLC intravenous (i.v.) because the TNLCGHG formulation contains surfactant with natural gelling polymers, which promisingly improved drug permeability. Finally, this research revealed encouraging outcomes and successfully developed intranasal TNLCGHG nanoformulation as a novel tool for safe delivery of TFM in glioma patients.

Matched MeSH terms: Administration, Intranasal
Intranasal Drug Delivery: A Non-Invasive Approach for the Better Delivery of Neurotherapeutics

Kumar H, Mishra G, Sharma AK, Gothwal A, Kesharwani P, Gupta U

Pharm Nanotechnol, 2017;5(3):203-214.
PMID: 28521670 DOI: 10.2174/2211738505666170515113936

BACKGROUND: The convoluted pathophysiology of brain disorders along with penetration issue of drugs to brain represents major hurdle that requires some novel therapies. The blood-brain barrier (BBB) denotes a rigid barrier for delivery of therapeutics in vivo; to overcome this barrier, intranasal delivery is an excellent strategy to deliver the drug directly to brain via olfactory and trigeminal nerve pathways that originate as olfactory neuro-epithelium in the nasal cavity and terminate in brain.
METHOD: Kind of therapeutics like low molecular weight drugs can be delivered to the CNS via this route. In this review, we have outlined the anatomy and physiological aspect of nasal mucosa, certain hurdles, various strategies including importance of muco-adhesive polymers to increase the drug delivery and possible clinical prospects that partly contribute in intranasal drug delivery.
RESULTS: Exhaustive literature survey related to intranasal drug delivery system revealed the new strategy that circumvents the BBB, based on non-invasive concept for treating various CNS disorders. Numerous advantages like prompt effects, self-medication through wide-ranging devices, and the frequent as well protracted dosing are associated with this novel route.
CONCLUSION: Recently few reports have proven that nasal to brain drug delivery system bypasses the BBB. This novel route is associated with targeting efficiency and less exposure of therapeutic substances to non-target site. Nevertheless, this route desires much more research into the safe transferring of therapeutics to the brain. Role of muco-adhesive polymer and surface modification with specific ligands are area of interest of researcher to explore more about this.

Matched MeSH terms: Administration, Intranasal
Lidocaine/Phenylephrine Nasal Spray versus Nebulization Prior to Nasoendoscopy: A Randomized Controlled Trial

Goh LC, Arvin B, Zulkiflee AB, Prepageran N

Otolaryngol Head Neck Surg, 2018 10;159(4):783-788.
PMID: 30126325 DOI: 10.1177/0194599818795852

Objective To objectively compare the nasal decongestion potency of lidocaine/phenylephrine when delivered with a nasal nebulizer and a nasal spray before a rigid nasoendoscopic examination. Study Design Open-label randomized controlled trial. Setting Multicenter study. Methods This prospective clinical trial involved 106 participants with untreated chronic rhinitis. Fifty-three participants had 400 μL of lidocaine/phenylephrine administered into the right nostril with a nasal nebulizer, while the remaining 53 participants had 400 μL administered with a nasal spray. The control was the left nostril. Nasal resistance at 150-Pa fixed pressure was evaluated with an active anterior rhinomanometry at 5, 10, 15, and 30 minutes postintervention. Pain score was assessed subjectively by applying pressure to the inferior turbinate 30 minutes after intervention. Results There was an overall reduction in nasal resistance of the right nostril when lidocaine/phenylephrine was administered with the nasal nebulizer in comparison with the nasal spray. However, a statistically significant difference in nasal resistance was seen only at 5 minutes ( P = .047), 15 minutes ( P = .016), and 30 minutes ( P = .036). The examining endoscopist further supported the degree of nasal decongestion via subjective assessment of the nasal cavity ( P = .001). Pain scores obtained after the intervention showed a significant decrease in pain threshold when the nasal nebulizer was used instead of the nasal spray ( P = .040). Conclusions This study suggests that the delivery of lidocaine/phenylephrine to the nasal cavity by the nasal nebulizer provides better decongestive and analgesic potency as compared with the delivery by nasal sprays.

Matched MeSH terms: Administration, Intranasal
Fulltext Esketamine Nasal Spray Plus Oral Antidepressant in Patients With Treatment-Resistant Depression: Assessment of Long-Term Safety in a Phase 3, Open-Label Study (SUSTAIN-2)

Wajs E, Aluisio L, Holder R, Daly EJ, Lane R, Lim P, et al.

J Clin Psychiatry, 2020 04 28;81(3).
PMID: 32316080 DOI: 10.4088/JCP.19m12891

OBJECTIVE: To evaluate long-term safety and efficacy of esketamine nasal spray plus a new oral antidepressant (OAD) in patients with treatment-resistant depression (TRD).
METHODS: This phase 3, open-label, multicenter, long-term (up to 1 year) study was conducted between October 2015 and October 2017. Patients (≥ 18 years) with TRD (DSM-5 diagnosis of major depressive disorder and nonresponse to ≥ 2 OAD treatments) were enrolled directly or transferred from a short-term study (patients aged ≥ 65 years). Esketamine nasal spray (28-mg, 56-mg, or 84-mg) plus new OAD was administered twice a week in a 4-week induction (IND) phase and weekly or every-other-week for patients who were responders and entered a 48-week optimization/maintenance (OP/MAINT) phase.
RESULTS: Of 802 enrolled patients, 86.2% were direct-entry and 13.8% were transferred-entry; 580 (74.5%) of 779 patients who entered the IND phase completed the phase, and 150 (24.9%) of 603 who entered the OP/MAINT phase completed the phase. Common treatment-emergent adverse events (TEAEs) were dizziness (32.9%), dissociation (27.6%), nausea (25.1%), and headache (24.9%). Seventy-six patients (9.5%) discontinued esketamine due to TEAEs. Fifty-five patients (6.9%) experienced serious TEAEs. Most TEAEs occurred on dosing days, were mild or moderate in severity, and resolved on the same day. Two deaths were reported; neither was considered related to esketamine. Cognitive performance generally either improved or remained stable postbaseline. There was no case of interstitial cystitis or respiratory depression. Treatment-emergent dissociative symptoms were transient and generally resolved within 1.5 hours postdose. Montgomery-Åsberg Depression Rating Scale total score decreased during the IND phase, and this reduction persisted during the OP/MAINT phase (mean [SD] change from baseline of respective phase to endpoint: IND, -16.4 [8.76]; OP/MAINT, 0.3 [8.12]).
CONCLUSIONS: Long-term esketamine nasal spray plus new OAD therapy had a manageable safety profile, and improvements in depression appeared to be sustained in patients with TRD.
TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02497287.

Matched MeSH terms: Administration, Intranasal

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