A Review on Modern Use of Intranasal Vaccination in the Treatment of SARS-COV-2

The coronavirus disease 2019 (COVID-19) pandemic has highlighted the urgent need for efficient SARS coronavirus 2 (SARS-CoV-2) preventative vaccines to limit the burden and spread of SARS-CoV-2 in humans. Intranasal immunization is a promising technique for preventing COVID-19 because the nasal mucosa acts as a first line of defense against SARS-CoV-2 entrance before the virus spreads to the lungs. Nasal vaccination has many advantages over traditional vaccine administration methods. These include the simplicity of administration without the use of needles, which decreases the risks of needle stick injuries and disposal. This channel also provides simple access to a crucial portion of the immune system that can stimulate other mucosal sites throughout the body. By targeting immunoglobulin A (IgA), antibodies found only in the mucosa, an intranasal vaccination would elicit immunological responses in the nose, throat, and lungs. Potential pathogens are trapped by the mucosa, which acts as a physical barrier to prevent them from entering the body. Given this, the intranasal vaccine would prevent virus transmission via exhaled droplets or aerosols because there would be no virus in the body to expel .There are several intranasal vaccines for protection against sars-cov2 are under preclinical and clinical trials .The key challenge is in Designing delivery strategies that take into account the wide range of diseases, populations, and healthcare delivery settings that stand to benefit from this unique mucosal route should be prioritized. Keywords: COVID-19, Intranasal vaccine, Immunoglobulin A, Permeation

Present Scenario of M-Cell Targeting Ligands for Oral Mucosal Immunization

The immune system plays an important role in the prevention of infection and forms the first line of defense against pathogen attack. Delivering of antigen through mucosal route may elicit mucosal immune system as the mucosal surface is the most common site of pathogen entry. Mucosal immune system will be capable to counter pathogen at mucosal surface. Oral mucosal immunization opens the ways to deliver antigens at gut-associated lymphoid tissue. This can elicit both local and systemic immune response. Mucosal vaccines are economical, highly accessible, non parenteral delivery and capacity to produce mass immunization at the time of pandemics. To deliver antigens on the mucosal surface of the gastrointestinal tract, the immune system relies on specialized epithelial cell i.e. Microfold (M)-cell. An approach to exploit the targeting specific receptors on M-cell for entry of antigens has made a breakthrough in vaccine development. In this review, various strategies have been discussed for the possible entry of antigens through M-cells and an approach to increase the uptake and efficacy of vaccines for oral mucosal immunization.

Defensive Driving: Directing HIV-1 Vaccine-Induced Humoral Immunity to the Mucosa with Chemokine Adjuvants

A myriad of pathogens gain access to the host via the mucosal route; thus, vaccinations that protect against mucosal pathogens are critical. Pathogens such as HIV, HSV, and influenza enter the host at mucosal sites such as the intestinal, urogenital, and respiratory tracts. All currently licensed vaccines mediate protection by inducing the production of antibodies which can limit pathogen replication at the site of infection. Unfortunately, parenteral vaccination rarely induces the production of an antigen-specific antibody at mucosal surfaces and thus relies on transudation of systemically generated antibody to mucosal surfaces to mediate protection. Mucosa-associated lymphoid tissues (MALTs) consist of a complex network of immune organs and tissues that orchestrate the interaction between the host, commensal microbes, and pathogens at these surfaces. This complexity necessitates strict control of the entry and exit of lymphocytes in the MALT. This control is mediated by chemoattractant chemokines or cytokines which recruit immune cells expressing the cognate receptors and adhesion molecules. Exploiting mucosal chemokine trafficking pathways to mobilize specific subsets of lymphocytes to mucosal tissues in the context of vaccination has improved immunogenicity and efficacy in preclinical models. This review describes the novel use of MALT chemokines as vaccine adjuvants. Specific attention will be placed upon the use of such adjuvants to enhance HIV-specific mucosal humoral immunity in the context of prophylactic vaccination.

Future drug delivery technologies: benchtop to industry

Transmucosal buccal drug delivery system is considered as a future drug delivery technology, always assist to enhance patient compliance mainly for paediatric and geriatric community. The studies aim to develop buccal delivery for delivering a hydrophilic drug, flucloxacillin sodium, across the mucosal route. The buccal films are comprised of a bio-adhesive polymer, plasticizer and drug. Optimised films were characterised by measurement of weight, length and width, hardness, thickness, surface pH, moisture content and uptake, swelling study, folding resilience, hydration and entrapment efficiency. Drug release studies were performed for different polymer-plasticizer-drug ratios. Concentration of polymer and plasticizer were influenced on the development, evaluation and release rate of flucloxacillin sodium from the buccal films. In conclusion, these studies reveal that buccal delivery of flucloxacillin sodium can be an alternative route in comparison to conventional route for patient compliance.IIUC Studies Vol.14(1) June 2017: 09-20

Oropharyngeal mucosal transmission of Zika virus in rhesus macaques

Zika virus (ZIKV) is present in urine, saliva, tears, and breast milk, but the transmission risk associated with these body fluids is currently unknown. We evaluated the risk of ZIKV transmission through mucosal contact in rhesus macaques. Application of high-dose ZIKV directly to the tonsils of 3 rhesus macaques resulted in detectable plasma viremia in all animals by 2 days post-exposure; virus replication kinetics were similar to those observed in animals infected subcutaneously. Three additional macaques inoculated subcutaneously with ZIKV served as saliva donors to assess the transmission risk from contact with oral secretions from an infected individual. Seven naive animals repeatedly exposed to donor saliva via the conjunctivae, tonsils, or nostrils did not become infected. Our results suggest that there is a risk of ZIKV transmission via the mucosal route, but that the risk posed by oral secretions from individuals with a typical course of ZIKV infection is low.

A REVIEW ON BUCCAL FILM: AN INOVATIVE DOSAGE FORM

Buccal administration of drugs leads to systemic circulation through internal jugular vein, bypassing them from hepatic first pass metabolism and leading to greater bioavailability. Buccal mucosa is most preferred site for both local as well as systemic action. For administration of drug through mucosal route, various types of dosage forms can be prepared. Buccal films can release topical drugs with controlled and sustained effects. Buccal films have the advantage of improved patient compliance because of reduced size with a suitable thickness as compare to other delivery systems. Buccal film can enhance absorption of active medicament as compared to others. Synthetic natural and semi synthetic polymers in low concentration can be used for the preparation of buccal films. Such types of dosage forms are cost effective, non-irritating, easy to handle, elegant, rapidly absorbable and most preferred by consumer. The review describes the anatomy of oral mucosa, mechanism of buccal absorption, methods to increase drug delivery via a buccal route, formulation aspects and evaluation parameters of buccal films.