Formulation of a dry powder influenza vaccine for nasal delivery

Garmise, Robert J.; Mar, Kevin D.; Crowder, Timothy M.; Hwang, C. Robin; Ferriter, Matthew; Huang, Juan; Mikszta, John A.; Sullivan, Vincent J.; Hickey, Anthony

doi:10.1208/pt070119

Cited by 41 publications

(22 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Pluronic® F-68 of different weights (25,50, and 100 mg) were placed into a micro-ball mill vessel (Dentsply Rinn Corporation, Elgin, IL, USA) containing a single stainless steel ball bearing of diameter~0.5 cm. The micro-ball mill, containing the powder was immersed in liquid nitrogen for 30 s and milled at various times (5, 10, and 15 min) for each weight of Pluronic® F-68 by placing the chamber in liquid nitrogen vapor.…”

Section: Air-jet Micronizationmentioning

confidence: 99%

“…For example, Chieng et al investigated the formation and stability of ranitidine hydrochloride amorphous state using cryo-milling performed with an oscillatory ball mill (26). Similarly, Garmise et al investigated dry powder vaccine formulations using chitosan as a mucoadhesive compound suitable for nasal delivery (25). The chitosan, a soft material, was reduced to sizes suitable for nasal delivery using a cryo-milling technique because chitosan was not brittle at room temperature.…”

Section: Cryo-micro-ball Millmentioning

confidence: 99%

“…Hence, liquid nitrogen was used to chill the milling chamber, prevent plastic deformation, and enhance the particle fracture process. Incorporation of liquid nitrogen (cryo-milling) is a common technique used for micronization of materials by a number of investigators (23,(25)(26)(27). Hence, comparisons were made between cryo-micro-ball milling and air-jet milling to achieve optimum conditions for micronization of Pluronic® F-68.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Micronization of a Soft Material: Air-Jet and Micro-Ball Milling

Saleem

Smyth

2010

AAPS PharmSciTech

View full text Add to dashboard Cite

Abstract. The air-jet and ball-mill are frequently used in fine micronization of active pharmaceutical ingredients to the order of 1-5 μm, which is important for increasing dissolution rates, and also for pulmonary delivery. In this study, we investigated the ability of air-jet and ball-mill to achieve adequate micronization on the lab scale using a model soft material, Pluronic® F-68. Material mechanical properties were characterized using the nanometer 600. Pluronic® F-68 was ball-milled in a micro-mill at different material weights and durations in liquid nitrogen vapor. In comparison, a lab scale air-jet mill was used at various milling parameters according to a full factorial design, where the response factors were particle yield and particle size distribution, which was analyzed using laser diffraction and scanning electron microscopy. The yield achieved with the micro-ball mill was 100% but was~80% for the air-jet mill, which reduced the size of Pluronic® F-68 from 70 μm to sizes ranging between 23-39 μm median diameters. Ball milling produced particles less than 10 μm after 15 min. Although air-jet milling proved capable of particle size reduction of the relatively soft material Pluronic® F-68, limitations to the lower size range achievable were observed. The feed rate of the material into the air jet mill was a significant factor and slower feed rates lead to smaller sizes by allowing more time for particle collisions and subsequent particle breakage to occur. Micro-ball milling under cold condition was more successful at achieving a lower range particle size reduction of soft materials.

show abstract

Section: Air-jet Micronizationmentioning

confidence: 99%

Section: Cryo-micro-ball Millmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Micronization of a Soft Material: Air-Jet and Micro-Ball Milling

Saleem

Smyth

2010

AAPS PharmSciTech

View full text Add to dashboard Cite

show abstract

“…Importantly, intranasal vaccination can be self‐administered and is needle‐free, thus facilitating an efficient mass‐vaccination regime and reducing the risk of accidental infection by blood‐borne pathogens 17 . Also, intranasal vaccination with influenza antigen resembles natural infection and can elicit both systemic and local immune responses 18 , 19 , 20 . The local mucosal antibodies limit epithelial contact and protect mucosal surfaces from invading infectious agents 21 .…”

Section: Introductionmentioning

confidence: 99%

The mucosal and systemic immune responses elicited by a chitosan‐adjuvanted intranasal influenza H5N1 vaccine

Svindland

Jul-Larsen

Pathirana

et al. 2011

Influenza Resp Viruses

View full text Add to dashboard Cite

Please cite this paper as: Svindland et al. The mucosal and systemic immune responses elicited by a chitosan‐adjuvanted intranasal influenza H5N1 vaccine. Influenza and Other Respiratory Viruses DOI:10.1111/j.1750‐2659.2011.00271.x. Background Development of influenza vaccines that induce mucosal immunity has been highlighted by the World Health Organisation as a priority (Vaccine 2005;23:1529). Dose‐sparing strategies and an efficient mass‐vaccination regime will be paramount to reduce the morbidity and mortality of a future H5N1 pandemic. Objectives This study has investigated the immune response and the dose‐sparing potential of a chitosan‐adjuvanted intranasal H5N1 (RG‐14) subunit (SU) vaccine in a mouse model. Methods Groups of mice were intranasally immunised once or twice with a chitosan (5 mg/ml)‐adjuvanted SU vaccine [7·5, 15 or 30 μg haemagglutinin (HA)] or with a non‐adjuvanted SU vaccine (30 μg HA). For comparison, another group of mice were intranasally immunised with a whole H5N1 (RG‐14) virus (WV) vaccine (15 μg HA), and the control group consisted of unimmunised mice. Results The chitosan‐adjuvanted SU vaccine induced an immune response superior to that of the non‐adjuvanted SU vaccine. Compared with the non‐adjuvanted SU group, the chitosan‐adjuvanted SU vaccine elicited higher numbers of influenza‐specific antibody‐secreting cells (ASCs), higher concentrations of local and systemic antibodies and correspondingly an improved haemagglutination inhibition (HI) and single radial haemolysis (SRH) response against both the homologous vaccine strain and drifted H5 strains. We measured a mixed T‐helper 1/T‐helper 2 cytokine response in the chitosan‐adjuvanted SU groups, and these groups had an increased percentage of virus‐specific CD4+ T cells producing two Thelper 1 (Th1) cytokines simultaneously compared with the non‐adjuvanted SU group. Overall, the WV vaccine induced higher antibody concentrations in sera and an HI and SRH response similar to that of the chitosan‐adjuvanted SU vaccine. Furthermore, the WV vaccine formulation showed a stronger bias towards a T‐helper 1 profile than the SU vaccine and elicited the highest frequencies of CD4+ Th1 cells simultaneously secreting three different cytokines (INFγ+, IL2+ and INFα+). As expected, two immunisations gave a better immune response than one in all groups. The control group had very low or not detectable results in the performed immunoassays. Conclusion The cross‐clade serum reactivity, improved B‐ and T‐cell responses and dose‐sparing potential of chitosan show that a chitosan‐adjuvanted intranasal influenza vaccine is a promising candidate vaccine for further preclinical development.

show abstract

“…37 Vibrational milling was for 15 minutes with milling speeds of 450 rpm, repeated three times at intervals of 3 minutes per grinding cycle. Milled powders were sieved with 300, 125, and 45 µm sieves.…”

Section: Preparation Of the Chi-tre-inactivated Nanoparticlesmentioning

confidence: 99%

Induction of mucosal immune responses and protection of cattle against direct-contact challenge by intranasal delivery with foot-and-mouth disease virus antigen mediated by nanoparticles

Pan¹,

Zhang²,

Lv³

et al. 2014

IJN

View full text Add to dashboard Cite

The aim of this study was to enhance specific mucosal, systemic, and cell-mediated immunity and to induce earlier onset of protection against direct-contact challenge in cattle by intranasal delivery of a nanoparticle-based nasal vaccine against type A foot-and-mouth disease (FMD). In this study, two kinds of nanoparticle-based nasal vaccines against type A FMD were designed: (1) chitosan-coated poly(lactic-co-glycolic acid) (PLGA) loaded with plasmid DNA (Chi-PLGA-DNA) and (2) chitosan-trehalose and inactivated foot-and-mouth disease virus (FMDV) (Chi-Tre-Inactivated). Cattle were immunized by an intranasal route with nanoparticles and then challenged for 48 hours by direct contact with two infected donor cattle per pen. Donors were inoculated intradermally in the tongue 48 hours before challenge, with 0.2 mL cattle-passaged FMDV. Serological and mucosal antibody responses were evaluated, and virus excretion and the number of contact infections were quantified. FMDV-specific secretory immunoglobulin (Ig)A (sIgA) antibodies in nasal washes were initially detected at 4 days postvaccination (dpv) with two kinds of nanoparticles. The highest levels of sIgA expression were observed in nasal washes, at 10 dpv, from animals with Chi-PLGA-DNA nanoparticles, followed by animals immunized once by intranasal route with a double dose of Chi-Tre-Inactivated nanoparticles and animals immunized by intranasal route three times with Chi-Tre-Inactivated nanoparticles ( P <0.05). FMDV-specific IgA antibodies in serum showed a similar pattern. All animals immunized by intranasal route developed low levels of detectable IgG in serum at 10 dpv. Following stimulation with FMDV, the highest levels of proliferation were observed in splenocytes harvested from Chi-PLGA-DNA-immunized animals, followed by proliferation of cells harvested from Chi-Tre-Inactivated nanoparticle-immunized animals ( P <0.05). Higher protection rates were associated with the highest sIgA antibody responses induced in the Chi-PLGA-DNA nanoparticle-immunized group. Only one animal was clinically affected with mild signs after 7 days of contact challenge, after a delay of 2–3 days compared with the clinically affected negative-control group. Of the five animals directly challenged that were vaccinated by intranasal route with a double dose of Chi-Tre-Inactivated, four were clinically infected; however, the degree of severity of disease in this group was lower than in control cattle. The number of viral RNA copies in nasal swabs from the vaccinated, severely infected group was significantly higher than in swabs from the vaccinated, clinically protected group. These data suggested that intranasal delivery of Chi-PLGA-DNA nanoparticles resulted in higher levels of mucosal, systemic, and cell-mediated immunity than did of Chi-Tre-Inactivated nanoparticles. In conclusion, although intranasal delivery with FMDV antigen mediated by nanoparticles did not provide complete clinical protection, it reduced disease severity and...

show abstract

Formulation of a dry powder influenza vaccine for nasal delivery

Cited by 41 publications

References 42 publications

Micronization of a Soft Material: Air-Jet and Micro-Ball Milling

Micronization of a Soft Material: Air-Jet and Micro-Ball Milling

The mucosal and systemic immune responses elicited by a chitosan‐adjuvanted intranasal influenza H5N1 vaccine

Induction of mucosal immune responses and protection of cattle against direct-contact challenge by intranasal delivery with foot-and-mouth disease virus antigen mediated by nanoparticles

Contact Info

Product

Resources

About