Determination of baseline human nasal pH and the effect of intranasally administered buffers

Washington, N.; Steele, Robert; Jackson, S.J; Bush, Debbie; Mason, J. D. T.; Gill, David A.; Pitt, Kendal; Rawlins, D. A.

doi:10.1016/s0378-5173(99)00442-1

Cited by 164 publications

(108 citation statements)

References 7 publications

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“…As the polymer would be in an expanded uncoiled state at the pH of the medium (6.2) due to the electrostatic repulsion arising from the ionized functional groups, the polymer would be more susceptible to mechanical chain entanglement and secondary interactions with the mucus glycoprotein. Owing to the presence of numerous carboxyl groups in g-PGA, the polymer is likely to be able to adopt a more favorable macromolecular conformation with increased accessibility of its hydrogen-bonding groups when compared with other polymers (40).…”

Section: Discussionmentioning

confidence: 99%

“…We speculated that g-PGA could interact with mucin molecules through physical chain entanglements and form hydrogen bonds with the sugar residues on the oligosaccharide chains (38,39). Because g-PGA is in the expanded uncoiled state at the pH of the nasal secretions (pH 6.0-6.5), the electrostatic repulsion arising from the ionized functional groups renders g-PGA more susceptible to mechanical chain entanglement and secondary interactions with the mucous glycoprotein (40). To determine the effect of CA-PMQ on inducing immune responses, OVA proteins, as model protein Ags, were administered through the i.n.…”

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confidence: 99%

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Programming of Influenza Vaccine Broadness and Persistence by Mucoadhesive Polymer-Based Adjuvant Systems

Noh

Chowdhury

Cho

et al. 2015

The Journal of Immunology

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The development of an anti-influenza vaccine with the potential for cross-protection against seasonal drift variants as well as occasionally emerging reassortant viruses is essential. In this study, we successfully generated a novel anti-influenza vaccine system combining conserved matrix protein 2 (sM2) and stalk domain of hemagglutinin (HA2) fusion protein (sM2HA2) and poly-γ-glutamic acid (γ-PGA)–based vaccine adjuvant systems that can act as a mucoadhesive delivery vehicle of sM2HA2 as well as a robust strategy for the incorporation of hydrophobic immunostimulatory 3-O-desacyl-4′-monophosphoryl lipid A (MPL) and QS21. Intranasal coadministration of sM2HA2 and the combination adjuvant γ-PGA/MPL/QS21 (CA-PMQ) was able to induce a high degree of protective mucosal, systemic, and cell-mediated immune responses. The sM2HA2/CA-PMQ immunization was able to prevent disease symptoms, confering complete protection against lethal infection with divergent influenza subtypes (H5N1, H1N1, H5N2, H7N3, and H9N2) that lasted for at least 6 mo. Therefore, our data suggest that mucosal administration of sM2HA2 in combination with CA-PMQ could be a potent strategy for a broad cross-protective influenza vaccine, and CA-PMQ as a mucosal adjuvant could be used for effective mucosal vaccines.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Programming of Influenza Vaccine Broadness and Persistence by Mucoadhesive Polymer-Based Adjuvant Systems

Noh

Chowdhury

Cho

et al. 2015

The Journal of Immunology

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“…Stability was confirmed by the negative zeta potential (Vyas et al, 2005(Vyas et al, , 2006bKumar et al 2008aKumar et al , 2008b. The pH of all the ME formulations was found to be in range of 5.4-5.5 and considered suitable for intranasal (Washington et al, 2000) and intravenous administration. TEM ( Figure 1A) micrograph of ME revealed spherical shape of the droplets and a size520 nm.…”

Section: Drug-loaded Microemulsionsmentioning

confidence: 90%

Docosahexaenoic acid–mediated, targeted and sustained brain delivery of curcumin microemulsion

Shinde

Devarajan

2017

Drug Delivery

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We disclose microemulsions (ME) of curcumin (CUR) with docosahexaenoic acid (DHA)-rich oil (CUR DHA ME) for targeted delivery to the brain. MEs of CUR (5 mg/mL) with and without DHArich oil (CUR Capmul ME) suitable for intravenous and intranasal administration exhibited negative zeta potential, globule size 520 nm and good stability. Following intravenous delivery MEs exhibited high brain concentration with CUR DHA ME exhibiting a 2.8-fold higher C max than CUR solution. Furthermore, high and sustained concentration was demonstrated even at 24 h, which was 8-and 2-fold higher than CUR solution and CUR Capmul ME, respectively. Brain concentrations following intranasal administration were, however, substantially higher as evident from higher C max and AUC and sustained compared to corresponding intravenous formulations signifying nose to brain targeting. The high brain concentration of CUR DHA ME is ascribed to the targeting efficiency enabled by DHA-mediated transport across the blood-brain barrier (BBB). Histopathological and nasal toxicity confirmed safety of the MEs. Concentrationdependent cytotoxicity in vitro, on human glioblastoma U-87MG cell line was observed with CUR DHA MEs and with the blank DHA ME, implying anticancer potential of DHA. The dramatically low IC 50 value of CUR DHA ME (3.755 ± 0.24 ng/mL) is therefore attributed to the synergistic effect of CUR and DHA in the ME. The CUR concentration achieved with CUR DHA ME at 24 h which translated to 466-fold(intranasal) and 421-fold (intravenous) the IC 50 value in the U-87MG cell line suggests great promise of CUR DHA ME for therapy of brain cancer by both routes.

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“…The degree of acidification of these surfaces in mammals varies depending on the distribution and activity of the submucosal glands. The pH of the human passageway has a range from 5.2 to 8.0 [13][14][15][16][17][18]. Therefore, the efficient infection of human URT cells requires a certain level of virus stability to acidic pH.…”

Section: Differences Between Human and Avian Influenza Virusesmentioning

confidence: 99%

Untitled

2017

MIR journal

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In order to decrease the morbidity and mortality caused by seasonal influenza outbreaks, several hundred million vaccine doses are produced worldwide each year. The predominant substrate for the production of the influenza vaccine today is fertilized hen's eggs. The substitution of the technology based on living organisms by the cell culture-based process offers many advantages, including easier scalability and reduced dependence on the availability of eggs. The African green monkey kidney and Madin Darby canine kidney cell lines support the efficient growth of influenza viruses of different subtypes and, therefore, are considered to be the two most promising alternative substrates for the production of the human influenza vaccine.However, the pH of endosomes in both of these cell lines is higher than the pH essential for triggering a conformational change of the hemagglutinin (HA) of human influenza viruses, which enables the viral-cellular membrane fusion. This mismatch gives rise to mutations in the HA that lead to an increase of the optimum pH of HA conformational change. As of a result of these mismatches, the HA, and consequently the whole virus, has reduced stability to low pH and elevated temperatures. The production of a vaccine from less stable virus will lead to an elevated HA content in the low pH conformation that can affect the safety, potency, infectivity, and protective efficacy of the final inactivated and live attenuated influenza vaccines.The main limitations of the cell line-based influenza vaccine technology and the possibilities to preserve the viral stability over the course of influenza vaccine production are discussed in the review.

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Determination of baseline human nasal pH and the effect of intranasally administered buffers

Cited by 164 publications

References 7 publications

Programming of Influenza Vaccine Broadness and Persistence by Mucoadhesive Polymer-Based Adjuvant Systems

Programming of Influenza Vaccine Broadness and Persistence by Mucoadhesive Polymer-Based Adjuvant Systems

Docosahexaenoic acid–mediated, targeted and sustained brain delivery of curcumin microemulsion

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