scholarly journals Short Onset and Enhanced Analgesia Following Nasal Administration of Non-Controlled Drugs in Nanovesicular Systems

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 978
Author(s):  
Elka Touitou ◽  
Hiba Natsheh ◽  
Shatha Boukeileh ◽  
Rania Awad
Keyword(s):  
Lipid Bilayers ◽  
Analgesic Effect ◽  
Drug Level ◽  
Nasal Delivery ◽  
Nasal Administration ◽  
Mice Model ◽  
Noninvasive Treatment ◽  
New Approach ◽  
Controlled Drugs ◽  
Peak Value

Nasal nanovesicular delivery systems (NVS) containing the noncontrolled analgesic drugs Ketoprofen, Butorphanol or Tramadol, incorporated in a phospholipid nanovesicular carrier, were designed and investigated. The systems were first characterized for their physicochemical properties. Due to their composition, comprising propylene glycol as a lipid bilayers fluidizer, these systems contain soft vesicles. Pharmacokinetic profiles of Tramadol in plasma and brain and of Ketoprofen in plasma were also assessed. The analgesic effect of each of the three tested drugs was evaluated in the acetic acid mice model for pain. One important result obtained in this work is that the concentration of Tramadol in rats’ plasma and brain increased rapidly after administration, reaching a peak value 10 min after administration with a Cmax of 2 to 5 folds greater than that for the oral or nasal non-vesicular treatments, respectively. In the case of Ketoprofen, the peak of the drug level in plasma was measured 10 min post nasal administration in NVS. The Cmax was three-fold higher relative to oral administration of this drug. In the experiment testing analgesia, a rapid and improved analgesia was observed for the tested drugs when delivered nasally in the nanocarrier. On the other hand, a weaker analgesic effect was observed for oral and nasal control systems. This new approach suggests that nasal delivery of non-controlled drugs in soft nanovesicles may open the way for better and noninvasive treatment of severe pain.

A prolactin-dependent sexually dimorphic mechanism of migraine chronification

Cephalalgia ◽  
2021 ◽  
pp. 033310242110398
Author(s):  
Daigo Ikegami ◽  
Edita Navratilova ◽  
Xu Yue ◽  
Aubin Moutal ◽  
Caroline M Kopruszinski ◽  
...  
Keyword(s):  
Trigeminal Ganglion ◽  
Medication Overuse ◽  
Medication Overuse Headache ◽  
Nasal Delivery ◽  
Nasal Administration ◽  
Dopamine Receptor Agonist ◽  
Sexually Dimorphic ◽  
Down Regulation ◽  
Female Mice ◽  
Cutaneous Allodynia

Objective Determination of possible sex differences in mechanisms promoting migraine progression and the contribution of prolactin and the prolactin long (PRLR-L) and short (PRLR-S) receptor isoforms. Background The majority of patients with chronic migraine and medication overuse headache are female. Prolactin is present at higher levels in women and increases migraine. Prolactin signaling at the PRLR-S selectively sensitizes nociceptors in female rodents, while expression of the PRLR-L is protective. Methods Medication overuse headache was modeled by repeated sumatriptan administration in male and female mice. Periorbital and hindpaw cutaneous allodynia served as a surrogate of migraine-like pain. PRLR-L and PRLR-S isoforms were measured in the trigeminal ganglion with western blotting. Possible co-localization of PRLR with serotonin 5HT1B and 5HT1D receptors was determined with RNAscope. Cabergoline, a dopamine receptor agonist that inhibits circulating prolactin, was co-administered with sumatriptan. Nasal administration of CRISPR/Cas9 plasmid was used to edit expression of both PRLR isoforms. Results PRLR was co-localized with 5HT1B or 5HT1D receptors in the ophthalmic region of female trigeminal ganglion. A single injection of sumatriptan increased serum PRL levels in female mice. Repeated sumatriptan promoted cutaneous allodynia in both sexes but down-regulated trigeminal ganglion PRLR-L, without altering PRLR-S, only in females. Co-administration of sumatriptan with cabergoline prevented allodynia and down-regulation of PRLR-L only in females. CRISPR/Cas9 editing of both PRLR isoforms in the trigeminal ganglion prevented sumatriptan-induced periorbital allodynia in females. Interpretation We identified a sexually dimorphic mechanism of migraine chronification that involves down-regulation of PRLR-L and increased signaling of circulating prolactin at PRLR-S. These studies reveal a previously unrecognized neuroendocrine mechanism linking the hypothalamus to nociceptor sensitization that increases the risk of migraine pain in females and suggest opportunities for novel sex-specific therapies including gene editing through nasal delivery of CRISPR/Cas9 constructs.

scholarly journals The electrophysiological mapping of compartments within a mammalian cell.

1977 ◽  
Vol 72 (1) ◽  
pp. 86-103 ◽  
Author(s):  
D Giulian ◽  
E G Diacumakos
Keyword(s):  
Electron Microscope ◽  
Electrical Properties ◽  
Intact Cell ◽  
Living Cells ◽  
Microscope Examination ◽  
New Approach ◽  
Golgi Region ◽  
Grounding Electrode ◽  
Combination Of Methods ◽  
Peak Value

The electrical properties of structures within an intact cell were examined by impalement with micropipette electrodes. Mean potential differences (PDs) measured from interphase HeLa cells showed that internal membrane-bounded compartments such as the nucleus, Golgi region, and the mitochondria were more negative than the cytoplasm with respect to an external grounding electrode. The nuclear PDs, unlike Golgi and cytoplasmic PDs, shifted during interphase and reached a peak value shortly before mitosis. The positioning of micropipettes was confirmed by electron microscope examination of marker solutions that were microinjected into specific intracellular regions. The combination of methods described here offers a new approach for the study of physiological events within intact, living cells.

FORMULATION AND IN-VITRO EVALUATION OF ZOLMITRIPTAN IN SITU GEL FOR NASAL ADMINISTRATION

INDIAN DRUGS ◽  
2013 ◽  
Vol 50 (12) ◽  
pp. 54-58
Author(s):  
P. H Patil ◽  
◽  
V. S Belgamwar ◽  
D. A Patel ◽  
S. J. Surana
Keyword(s):  
Evaluation Studies ◽  
Methyl Cellulose ◽  
Nasal Delivery ◽  
Nasal Administration ◽  
Histopathological Study ◽  
In Situ Gel ◽  
In Vitro Evaluation ◽  
Effective Delivery

The aim of present investigation was formulation and in-vitro evaluation of in situ gel for the nasal delivery of zolmitriptan. The in situ gel was prepared by temperature induced gelation technique using Pluronic with mucoadhesive polymer hydroxy propyl methyl cellulose K4 M in different ratios. The in situ gels so prepared were characterized and from the evaluation studies, batch PH2 was optimized and further subjected for stability studies at 30±2°C and 60±5% RH for 90 days. These formulations retained good stability at accelerated conditions and also did not show any remarkable damage to nasal mucosa in histopathological study. Owing to these properties it can be used as an effective delivery system for the nasal route.

scholarly journals A new approach for the fabrication of microscale lipid bilayers at glass pipets: application to quantitative passive permeation visualization

Soft Matter ◽  
2014 ◽  
Vol 10 (42) ◽  
pp. 8433-8441 ◽  
Author(s):  
Katherine E. Meadows ◽  
Binoy Paulose Nadappuram ◽  
Patrick R. Unwin
Keyword(s):  
Lipid Bilayers ◽  
New Approach

scholarly journals Experimental Validation of Molecular Dynamics Simulations of Lipid Bilayers: A New Approach

2005 ◽  
Vol 88 (2) ◽  
pp. 805-817 ◽  
Author(s):  
Ryan W. Benz ◽  
Francisco Castro-Román ◽  
Douglas J. Tobias ◽  
Stephen H. White
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Lipid Bilayers ◽  
Experimental Validation ◽  
New Approach ◽  
Dynamics Simulations

Nasal administration of nanoencapsulated geraniol/ursodeoxycholic acid conjugate: Towards a new approach for the management of Parkinson's disease

2020 ◽  
Vol 321 ◽  
pp. 540-552 ◽  
Author(s):  
Edilson Ribeiro de Oliveira Junior ◽  
Eleonora Truzzi ◽  
Luca Ferraro ◽  
Marco Fogagnolo ◽  
Barbara Pavan ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Ursodeoxycholic Acid ◽  
Nasal Administration ◽  
New Approach ◽  
Acid Conjugate

scholarly journals A New Natural Defense Against Airborne Pathogens

QRB Discovery ◽  
2020 ◽  
Vol 1 ◽  
Author(s):  
David Edwards ◽  
Anthony Hickey ◽  
Richard Batycky ◽  
Lester Griel ◽  
Michael Lipp ◽  
...  
Keyword(s):  
Primary Source ◽  
Face Mask ◽  
Nasal Delivery ◽  
Nasal Administration ◽  
Swine Model ◽  
Upper Airways ◽  
Suppression Effect ◽  
High Particle ◽  
Natural Defense ◽  
Human Airways

AbstractWe propose the nasal administration of calcium-enriched physiological salts as a new hygienic intervention with possible therapeutic application as a response to the rapid and tenacious spread of COVID-19. We test the effectiveness of these salts against viral and bacterial pathogens in animals and humans. We find that aerosol administration of these salts to the airways diminishes the exhalation of the small particles that face masks fail to filter and, in the case of an influenza swine model, completely block airborne transmission of disease. In a study of 10 human volunteers (5 less than 65 years and 5 older than 65 years), we show that delivery of a nasal saline comprising calcium and sodium salts quickly (within 15 min) and durably (up to at least 6 h) diminishes exhaled particles from the human airways. Being predominantly smaller than 1 μm, these particles are below the size effectively filtered by conventional masks. The suppression of exhaled droplets by the nasal delivery of calcium-rich saline with aerosol droplet size of around 10 μm suggests the upper airways as a primary source of bioaerosol generation. The suppression effect is especially pronounced (99%) among those who exhale large numbers of particles. In our study, we found this high-particle exhalation group to correlate with advanced age. We argue for a new hygienic practice of nasal cleansing by a calcium-rich saline aerosol, to complement the washing of hands with ordinary soap, use of a face mask, and social distancing.

scholarly journals Selective targeting of the TLR2/MyD88/NF-κB pathway reduces α-synuclein spreading in vitro and in vivo

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Debashis Dutta ◽  
Malabendu Jana ◽  
Moumita Majumder ◽  
Susanta Mondal ◽  
Avik Roy ◽  
...  
Keyword(s):  
Lewy Bodies ◽  
Selective Inhibition ◽  
Nasal Delivery ◽  
Nasal Administration ◽  
Interaction Domain ◽  
Selective Targeting ◽  
Nemo Binding Domain ◽  
Microglial Inflammation

AbstractPathways to control the spreading of α-synuclein (α-syn) and associated neuropathology in Parkinson’s disease (PD), multiple system atrophy (MSA) and dementia with Lewy bodies (DLB) are unclear. Here, we show that preformed α-syn fibrils (PFF) increase the association between TLR2 and MyD88, resulting in microglial activation. The TLR2-interaction domain of MyD88 (wtTIDM) peptide-mediated selective inhibition of TLR2 reduces PFF-induced microglial inflammation in vitro. In PFF-seeded A53T mice, the nasal administration of the wtTIDM peptide, NEMO-binding domain (wtNBD) peptide, or genetic deletion of TLR2 reduces glial inflammation, decreases α-syn spreading, and protects dopaminergic neurons by inhibiting NF-κB. In summary, α-syn spreading depends on the TLR2/MyD88/NF-κB pathway and it can be reduced by nasal delivery of wtTIDM and wtNBD peptides.

scholarly journals Enhancement of the immunogenicity of a Mycobacterium tuberculosis fusion protein using ISCOMATRIX and PLUSCOM nano-adjuvants after nasal administration in mice

2021 ◽  
Author(s):  
Arshid Yousefi Avarvand ◽  
Zahra Meshkat ◽  
Farzad Khademi ◽  
Ehsan Aryan ◽  
Mojtaba Sankian ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Immune Responses ◽  
Fusion Protein ◽  
Intranasal Administration ◽  
Bacterial Infections ◽  
Protective Efficacy ◽  
Nasal Administration ◽  
Mice Model ◽  
Ifn Γ ◽  
Nasal Immunization

Background: Tuberculosis (TB), a contagious disease caused by Mycobacterium tuberculosis (M. tuberculosis), remains a health problem worldwide and this infection has the highest mortality rate among bacterial infections. Current studies suggest that intranasal administration of new tuberculosis vaccines could enhance the immunogenicity of M. tuberculosis antigens. Hence, we aim to evaluate the protective efficacy and immunogenicity of HspX/EsxS fusion protein of M. tuberculosis along with ISCOMATRIX and PLUSCOM nano-adjuvants and MPLA through the intranasal administration in mice model. Methods:In present study, the recombinant fusion protein was expressed in Escherichia coli and purified and used to prepare different nanoparticle formulations in combination with ISCOMATRIX and PLUSCOM nano-adjuvants and MPLA. Mice were intranasally vaccinated with each formulation three times at an interval of 2 weeks. Finally, IFN-γ, IL-4. IL-17 and TGF-β concentration in supernatant of cultured splenocytes of vaccinated mice as well as serum titers of IgG1 and IgG2a and sIgA titers in nasal lavage were determined. Results:According to obtained results, intranasally vaccinated mice with formulations containing ISCOMATRIX and PLUSCOM nano-adjuvants and MPLA could effectively induced IFN-γ and sIgA responses. Moreover, both HspX/EsxS/ISCOMATRIX/MPLA and HspX/EsxS/PLUSCOM/MPLA and their BCG booster formulation could strongly stimulate the immune system and enhance the immunogenicity of M. tuberculosis antigens. Conclusion: The results demonstrate the potential of HspX/EsxS-fused protein in combination with ISCOMATRIX, PLUSCOM and MPLA after nasal administration in enhancing immune response against of M. tuberculosis antigens. So, nasal immunization with these formulations, could induce immune responses and considered as new TB vaccine or as BCG booster.

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