scholarly journals Evaluation of the Pharmacokinetics of Intranasal Drug Delivery for Targeting Cervical Lymph Nodes in Rats

Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1363
Author(s):  
Tomoyuki Furubayashi ◽  
Daisuke Inoue ◽  
Shunsuke Kimura ◽  
Akiko Tanaka ◽  
Toshiyasu Sakane

A well-developed lymphatic network is located under the nasal mucosa, and a few drugs that permeate the nasal mucosa are absorbed into the lymphatic capillaries. Lymph from the nasal cavity flows to the cervical lymph nodes (CLNs). In this study, we evaluated the pharmacokinetics of the direct transport of intranasally administered drugs to CLNs through the nasal mucosa of Wistar rats using methotrexate as a model drug. The drug targeting index, which was calculated based on the areas under the concentration–time curves after intravenous and intranasal administration, was 3.78, indicating the benefits of nasal delivery of methotrexate to target CLNs. The direct transport percentage, which was indicative of the contribution of the direct nose–CLN pathway of methotrexate after intranasal administration, was 74.3%. The rate constant of methotrexate from the nasal cavity to CLNs was 0.0047 ± 0.0013 min−1, while that from systemic circulation to CLNs was 0.0021 ± 0.0009 min−1. Through pharmacokinetic analysis, this study demonstrated that the direct nasal–CLN pathway contributed more to the transport of methotrexate to the CLNs than the direct blood–CLN pathway.

2006 ◽  
Vol 80 (4) ◽  
pp. 797-801 ◽  
Author(s):  
Jana Goldmann ◽  
Erik Kwidzinski ◽  
Christine Brandt ◽  
Jacqueline Mahlo ◽  
Daniel Richter ◽  
...  

2007 ◽  
Vol 81 (9) ◽  
pp. 4482-4491 ◽  
Author(s):  
Anthony E. Kincaid ◽  
Jason C. Bartz

ABSTRACT Animals that naturally acquire the prion diseases have a well-developed olfactory sense that they utilize for a variety of basic behaviors. To assess the potential for the nasal cavity to serve as a point of entry for prion diseases, a small amount of prion-infected brain homogenate was placed inferior to the nostrils of hamsters, where it was immediately sniffed into the nasal cavity. Hamsters extranasally inoculated with the HY strain of transmissible mink encephalopathy (TME) agent had an incubation period that was not significantly different from per os inoculation of the same dose of the HY TME agent. However, the efficiency of the nasal route of inoculation was determined to be 10 to 100 times greater based on endpoint dilution analysis. Immunohistochemistry on tissues from hamsters killed at 2-week intervals after inoculation was used to identify the disease-associated form of the prion protein (PrPd) to determine the route of prion neuroinvasion. Nasal mucosa-associated lymphoid tissue and submandibular lymph nodes initially accumulated PrPd as early as 4 weeks postinfection. PrPd was first identified in cervical lymph nodes at 8 weeks, in the mesenteric lymph nodes, spleen, and Peyer's patches at 14 weeks, and in the tongue 20 weeks after inoculation. Surprisingly, there was no evidence of PrPd in olfactory epithelium or olfactory nerve fascicles at any time after inoculation. Therefore, the HY TME agent did not enter the central nervous system via the olfactory nerve; instead, PrPd accumulated in elements of the cranial lymphoreticular system prior to neuroinvasion.


2015 ◽  
Vol 8 (1) ◽  
pp. 43-45
Author(s):  
Kiran Mishra ◽  
Lakshmi Vaid ◽  
Vivek Gogia

ABSTRACT Sinus histiocytosis with massive lymphadenopathy (SHML) (also known as Rosai-Dorfman syndrome) is a rare, idiopathic, benign and self-limiting histiocytic proliferative disorder. It most commonly involves the cervical lymph nodes. The disease has a benign course and involvement of the nasal cavity as an extranodal site is exceptional. Here, we report a case of bilateral sinonasal mass with subsequent involvement of cervical lymph nodes in 22-year-old lady. Histological examination of the cervical lymph nodes and nasal mass biopsy demonstrated evidences of Rosai-Dorfman disease (RDD). The clinical presentation, histologic characteristics, radiographic findings and treatment of the disease are discussed. How to cite this article Vaid L, Jain N, Gogia V, Mishra K. Sinonasal Manifestation of Rosai-Dorfman Syndrome. Clin Rhinol An Int J 2015;8(1):43-45.


2006 ◽  
Vol 74 (5) ◽  
pp. 2760-2766 ◽  
Author(s):  
Donata Medaglini ◽  
Annalisa Ciabattini ◽  
Anna Maria Cuppone ◽  
Caterina Costa ◽  
Susanna Ricci ◽  
...  

ABSTRACT The antigen-specific primary activation of CD4+ T cells was studied in vivo by adoptive transfer of ovalbumin-specific transgenic T cells (KJ1-26+ CD4+) following intranasal immunization with recombinant Streptococcus gordonii. A strain of S. gordonii expressing on its surface a model vaccine antigen fused to the ovalbumin (OVA) peptide from position 323 to 339 was constructed and used to study the OVA-specific T-cell activation in nasal mucosa-associated lymphoid tissue (NALT), lymph nodes, and spleens of mice immunized by the intranasal route. The recombinant strain, but not the wild type, activated the OVA-specific CD4+ T-cell population in the NALT (89% of KJ1-26+ CD4+ T cells) just 3 days following immunization. In the cervical lymph nodes and in the spleen, the percentage of proliferating cells was initially low, but it reached the peak of activation at day 5 (90%). This antigen-specific clonal expansion of KJ1-26+ CD4+ T cells after intranasal immunization was obtained with live and inactivated recombinant bacteria, and it indicates that the NALT is the site of antigen-specific T-cell priming.


Author(s):  
Hyung Chae Yang ◽  
Eun Jeong Won ◽  
Moon-Ju Kim ◽  
Chung Man Sung ◽  
Joon Haeng Rhee ◽  
...  

<b><i>Objectives:</i></b> This study aimed to evaluate potential therapeutic effect of <i>Metagonimus yokogawai</i> on the OVA-induced allergic rhinitis model. <b><i>Methods:</i></b> OVA-sensitized mice were used to assess potential therapeutic effect of the extract protein of <i>M. yokogawai</i> (My-TP). My-TP was administrated via the intralymphatic route to cervical lymph nodes. The frequencies of sneezing or nasal rubbing were recorded. Histopathologic evaluation was performed for eosinophil infiltrations in the tissues of the nasal mucosa and skin. The mRNA relative expressions of the cytokine profiles including Th1, Th2, Th17, and Treg subsets in the nasal mucosa, cervical lymph nodes, and spleen were analyzed by quantitative real-time reverse-transcriptase polymerase chain reaction. The potential underlying mechanism was investigated by examining cytokine profiles including IL-4 and Treg subsets from lymphocytes of the spleen by flow cytometry. <b><i>Results:</i></b> Intralymphatic injection of My-TP reduced allergic symptoms and eosinophil infiltration in the nasal mucosa. My-TP-treated group showed markedly decreased levels of OVA-specific IgE and WBC counts in nasal lavage. My-TP-treated group showed the decreased expression levels of IL-4, while those of IL-10 were increased in both the nasal mucosa. The levels of IFN-γ and IL-17 were also decreased in the nasal mucosa and cervical lymph nodes. The immunological mechanism may involve the downregulation of Th2 response and upregulation of Tregs in the nasal mucosa and cervical lymph nodes. <b><i>Conclusions:</i></b> Our results provide the first evidence of potential therapeutic effect of <i>M. yokogawai</i> in OVA-sensitized allergic rhinitis mice, suggesting that a Treg/Th2 reorganization may play a role in clinical course of allergic rhinitis.


2006 ◽  
Vol 74 (1) ◽  
pp. 694-702 ◽  
Author(s):  
Shee Eun Lee ◽  
Soo Young Kim ◽  
Byung Chul Jeong ◽  
Young Ran Kim ◽  
Soo Jang Bae ◽  
...  

ABSTRACT Flagellin, the structural component of flagellar filament in various locomotive bacteria, is the ligand for Toll-like receptor 5 (TLR5) of host cells. TLR stimulation by various pathogen-associated molecular patterns leads to activation of innate and subsequent adaptive immune responses. Therefore, TLR ligands are considered attractive adjuvant candidates in vaccine development. In this study, we show the highly potent mucosal adjuvant activity of a Vibrio vulnificus major flagellin (FlaB). Using an intranasal immunization mouse model, we observed that coadministration of the flagellin with tetanus toxoid (TT) induced significantly enhanced TT-specific immunoglobulin A (IgA) responses in both mucosal and systemic compartments and IgG responses in the systemic compartment. The mice immunized with TT plus FlaB were completely protected from systemic challenge with a 200× minimum lethal dose of tetanus toxin. Radiolabeled FlaB administered into the nasal cavity readily reached the cervical lymph nodes and systemic circulation. FlaB bound directly to human TLR5 expressed on cultured epithelial cells and consequently induced NF-κB and interleukin-8 activation. Intranasally administered FlaB colocalized with CD11c as patches in putative dendritic cells and caused an increase in the number of TLR5-expressing cells in cervical lymph nodes. These results indicate that flagellin would serve as an efficacious mucosal adjuvant inducing protective immune responses through TLR5 activation.


JAMA ◽  
1965 ◽  
Vol 194 (1) ◽  
pp. 1-4 ◽  
Author(s):  
A. D. Nicastri

2013 ◽  
Vol 1 (2) ◽  
pp. 02-06
Author(s):  
SM Anwar Sadat ◽  
Sufia Nasrin Rita ◽  
Shoma Banik ◽  
Md Nazmul Hasan Khandker ◽  
Md Mahfuz Hossain ◽  
...  

A cross sectional study of 29 cases of oral squamous cell carcinoma with or without  cervical lymph node metastasis was done among Bangladeshi patients from January 2006 to December 2007. Majority of the study subjects (34.5%) belonged to the age group of 40-49 years. 58.6% of the study subjects were male, while remaining 41.4% of them were female. 51.7% of the lesions were located in the alveolar ridge where the other common sites were buccal mucosa (27.6%) and retro molar area (13.8%). Half of the study subjects (51.7%) were habituated to betel quid chewing followed by 37.9% and 10.3% were habituated to smoking and betel quid-smoking respectively. Grade I lesions was most prevalent (75.9%) in the study subjects.  Majority of cases presented with Stage IV lesions (55.2%). The sensitivity, specificity, positive predictive value, negative predictive value & accuracy of clinical palpation method for determining metastatic cervical lymph nodes were 93.33%, 64.29%, 73.68%, 90% and 79.3% respectively. Careful and repeated clinical palpation plays important role in evaluation of cervical lymph nodes though several modern techniques may help additionally in the management of oral cancer.DOI: http://dx.doi.org/10.3329/updcj.v1i2.13978 Update Dent. Coll. j. 2011: 1(2): 02-06


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