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Non-NK group 1 innate lymphoid cells (ILC1s), mainly investigated in the mucosal areas of the intestine, are well-known to contribute to anti-parasitic and anti-bacterial immune responses. Recently, our group revealed that lung ILC1s become activated during murine influenza infection, thereby contributing to viral clearance. In this context, worldwide seasonal influenza infections often result in severe disease outbreaks leading to high morbidity and mortality. Therefore, new immune interventions are urgently needed. In contrast to NK cells, the potential of non-NK ILC1s to become functionally tailored by immune modulators to contribute to the combat against mucosal-transmitted viral pathogens has not yet been addressed. The present study aimed at assessing the potential of ILC1s to become modulated by iNKT cells activated through the CD1d agonist αGalCerMPEG. Our results demonstrate an improved functional responsiveness of murine lung and splenic ILC1s following iNKT cell stimulation by the mucosal route, as demonstrated by enhanced surface expression of TNF-related apoptosis-inducing ligand (TRAIL), CD49a and CD28, and increased secretion of IFNγ. Interestingly, iNKT cell stimulation also induced the expression of the immune checkpoint molecules GITR and CTLA-4, which represent crucial points of action for immune regulation. An in vivo influenza infection model revealed that intranasal activation of ILC1s by αGalCerMPEG contributed to increased viral clearance as shown by reduced viral loads in the lungs. The findings that ILC1s can become modulated by mucosally activated iNKT cells in a beneficial manner emphasize their up to now underestimated potential and renders them to be considered as targets for novel immune interventions.

Non-NK group 1 innate lymphoid cells (ILC1s), mainly investigated in the mucosal areas of the intestine, are well-known to contribute to anti-parasitic and anti-bacterial immune responses. Recently, our group revealed that lung ILC1s become activated during murine influenza infection, thereby contributing to viral clearance. In this context, worldwide seasonal influenza infections often result in severe disease outbreaks leading to high morbidity and mortality. Therefore, new immune interventions are urgently needed. In contrast to NK cells, the potential of non-NK ILC1s to become functionally tailored by immune modulators to contribute to the combat against mucosal-transmitted viral pathogens has not yet been addressed. The present study aimed at assessing the potential of ILC1s to become modulated by iNKT cells activated through the CD1d agonist αGalCerMPEG. Our results demonstrate an improved functional responsiveness of murine lung and splenic ILC1s following iNKT cell stimulation by the mucosal route, as demonstrated by enhanced surface expression of TNF-related apoptosis-inducing ligand (TRAIL), CD49a and CD28, and increased secretion of IFNγ. Interestingly, iNKT cell stimulation also induced the expression of the immune checkpoint molecules GITR and CTLA-4, which represent crucial points of action for immune regulation. An in vivo influenza infection model revealed that intranasal activation of ILC1s by αGalCerMPEG contributed to increased viral clearance as shown by reduced viral loads in the lungs. The findings that ILC1s can become modulated by mucosally activated iNKT cells in a beneficial manner emphasize their up to now underestimated potential and renders them to be considered as targets for novel immune interventions. [ABSTRACT FROM AUTHOR]

The aim was to formulate an optimized ursolic acid (UA) loaded lipid vesicle using formulation by design approach (FbD) for improving the drug targeting by nasal route for brain tumor. Three factors were evaluated at three different levels using anethole (terpene) (A), ethanol (B) and phospholipid90 G (C) as independent variables and their individual and combined effects were observed for PDI (Y 1 ), vesicle size (Y 2 ) and encapsulation efficiency (Y 3 ) to select an optimal system (UALVopt). The optimized formulation was further converted into gel and evaluated for drug release, nasal permeation study, brain/plasma uptake and histopathology study. The UALVopt formulation containing anethole as terpene (1% as A), ethanol (2.6% as B) and phospholipid90 G (8.8 mg as C) showed low PDI (0.212), vesicle size (115.56 nm) and high entrapment efficiency (76.42%). The in-vitro drug release and ex-vivo permeation study results revealed prolonged drug release and permeation. The brain/blood ratio for UALVGopt remained significantly higher at all the time points with respect to UALVopt indicating higher and prolonged retention of drug at site of action. The histopathological study of the nasal mucosa and brain confirmed non-toxic nature of developed formulation. The formulation UALVGopt could serve as a better alternative for the brain targeting via the intranasal route which in turn could subsequently improve its efficacy. [ABSTRACT FROM AUTHOR]

The present work discusses the preparation, characterization and in vivo evaluation of thiolated chitosan nanoparticles (TCS-NPs) of buspirone hydrochloride (BUH) for brain delivery through intranasal route. TCS NPs were prepared by ionic gelation method and characterized for various parameters. The NPs formed were having particle size of 226.7 ± 2.52 nm with PDI 0.483 ± 0.031. Drug entrapment efficiency (EE) and loading capacity (LC) were found to be 81.13 ± 2.8 and 49.67 ± 5.5%. The cumulative percentage drug permeation through nasal mucosa was 76.21%. Bioadhesion study carried out on porcine mucin and showed a bioadhesion efficiency of 90.218 ± 0.134%. Nose-to-brain delivery of placebo NPs was investigated by confocal laser scanning microscopy (CLSM) technique using rhodamine-123 as a marker. The brain concentration achieved after intranasal administration of TCS-NPs was 797.46 ± 35.76 ng/ml with t max 120 min which was significantly higher than achieved after intravenous administration on BUH solution 384.15 ± 13.42 ng/ml and t max of 120 min and intranasal administration of BUH solution 417.77 ± 19.24 ng/ml and t max 60 min. [ABSTRACT FROM AUTHOR]

Objective: The objective of the present study was to investigate the potential use of solid lipid nanoparticles (SLNs) as a drug delivery system to enhance the brain-targeting efficiency of rosmarinic acid (RA) following intranasal (i.n.) administration. Materials and methods: The RA-loaded SLNs was prepared by the hot homogenization technique, in which glycerol monostearate (GMS) as lipid, tween 80 and soya lecithin were used as surfactant along with hydrogenated soya phosphatidyl choline (HSPC) as a stabilizer, and were characterized for particle size, zeta potential (ZP),in vitrostudy. Nasal delivery of the developed formulation followed by the study of behavioral (locomotor, narrow beam, body weight) and biochemical parameters (glutathione, lipid peroxidation, catalase and nitrite) in wistar rat was carried out. Results:Optimized RA-loaded SLNs using tween 80 (SLNPRT) have the mean size of (149.2 ± 3.2 nm), ZP (−38.27 mV) entrapment efficiency (61.9 ± 2.2%). 3-NP-treated rat significantly increased behavioral alterations, oxidative damage as compared with the control group. SLNPRT treatment significantly improved behavioral abnormalities and attenuated the oxidative stress in 3NP-treated rats. However, the nasal delivery of SLNPRT produced significant therapeutic action as compared to intravenous application. In the organ distribution study, brain drug concentration was found to be 5.69 µg, in pharmacokinetic studyCmax,tmax,t1/2, AUC values were found to be 0.284 µg/ml, 1.5 h, 3.17 h, and 1.505 µg/ml/h, respectively. Conclusion: The encouraging results confirmed the developed optimized RA-loaded SLNs formulation following the non-invasive nose-to-brain drug delivery that is a promising therapeutic approach for the effective management in Huntington disease. [ABSTRACT FROM PUBLISHER]

Anisakis (Anisakidae) is one of the most important causes of helminth-induced allergic reactions and elicits clinical responses that include urticaria, rhinitis, bronco-constriction, cough, and/or gastrointestinal symptoms. More than 13 reactive allergens have been identified in the serum of Anisakis allergy patients, but the allergenicity of only a few of these have been evaluated in vivo using a mouse model. To evaluate the allergenicity of two important allergens, Ani s 1 and Ani s 9, we induced experimental allergic airway inflammation in a mouse model by repeated intranasal administration of the allergens. Both recombinant proteins (rAni s 1 and rAni s 9) elicited increased airway hyperresponsivity, airway infiltration by inflammatory cells (especially eosinophils), bronchial epithelial cell hyperplasia, all of which are characteristic of allergic airway inflammation. These allergens significantly increased the levels of Th2-related cytokines (IL-4, IL-5, IL-13, and IL-25) and Th17 related cytokines (IL-6 and IL-17) in both splenocytes and airway (except IL-17 in airway by rAni s 9). OVA-specific IgE and total IgE were increased in rAni s 1 and rAni s 9 treated mice as compared with controls treated with OVA alone. In addition, these two allergens induced gene expression of thymic stromal lymphopoietin (TSLP) and IL-25 (initiators of the Th2 response), as well as CXCL1 (initiator of the Th17 response) in mouse lung epithelial cells. In conclusion, repeated intranasal treatments with rAni s 1 and rAni s 9 induced airway inflammation in mice by elevating of Th2 and Th17 responses in the lung. [ABSTRACT FROM AUTHOR]

Background: Orofacial pain is a common encounter in dentistry (affecting 12% of the population) and is a primary reason for patients seeking emergency care. Dentists often prescribe oral analgesics, which have disadvantages of decreased absorption rates and delayed onset. Intranasal (IN) delivery takes advantage of a large surface area of mucosal tissue for rapid absorption. The purpose of this study was to evaluate the efficacy of IN ketorolac for endodontic pain using a randomized, double-blind, placebocontrolled parallel design study. Materials & Methods: Twenty patients presenting with moderate to severe endodontic pain were selected to receive IN treatment with placebo (n = 10) or ketorolac (n = 10) 30 minutes before endodontic treatment was started and immediately after the completion of endodontic treatment. Baseline pain levels were recorded before IN treatment. Pain levels were also recorded at 15 and 30 minutes after the initial IN dosing (before endodontic treatment); 30 minutes after completion of endodontic treatment; and 4, 8, and 12 hours after the initial IN spray. Results: IN ketorolac alone or with endodontic treatment showed significantly better pain relief compared with IN placebo spray alone or with endodontic treatment at 30 minutes after the first or second intranasal dose and at 4 hours after the first intranasal dose. Conclusions: These results suggest that IN ketorolac may provide a novel and efficacious method for pain relief in endodontic pain patients. [ABSTRACT FROM AUTHOR]

Abstract: The nasal mucosa has many advantages as a potential site for drug and vaccine delivery. The present study has sought to exploit this route of delivery using microparticles composed of d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) as a matrix material blended with poly(caprolactone) for nasal immunisation with diphtheria toxoid. Particles were prepared by a double emulsion method, followed by spray drying and the effect of TPGS on size, zeta potential, loading and release of antigen was assessed. Particles composed of TPGS–PCL blends were spherical, smooth and monodisperse, displaying increasing yields after spray drying with increasing concentrations of TPGS. The immune response to diphtheria toxoid loaded PCL-TPGS microspheres after nasal administration was shown to be higher than that achieved using PCL microspheres alone. We conclude that TPGS shows significant potential as a novel adjuvant either alone or in combination with an appropriate delivery system. [Copyright &y& Elsevier]

The development of age-appropriate formulations should focus on dosage forms that can deliver variable yet accurate doses that are safe and acceptable to the child, are matched to his/her development and ability, and avoid medication errors. However, in the past decade, the medication needs of neonates have largely been neglected. The aim of this review is to expand on what differentiates the needs of preterm and term neonates from those of the older paediatric subsets, in terms of environment of care, ability to measure and administer the dose (from the perspective of the patient and carer, the routes of administration, the device and the product), neonatal biopharmaceutics and regulatory challenges. This review offers insight into those challenges posed by the formulation of medicinal products for neonatal patients in order to support the development of clinically relevant products. [ABSTRACT FROM AUTHOR]