Article

Design of nanoparticle-based dry powder pulmonary vaccines.

Graduate Program in Biophysics, Harvard University Faculty of Arts and Sciences, 40 Oxford Street, ESL 406, Cambridge, MA 02138, USA.
Expert Opinion on Drug Delivery (impact factor: 4.9). 12/2007; 4(6):651-63. DOI:10.1517/17425247.4.6.651
Source: PubMed

ABSTRACT The development of needle-less vaccination for pulmonary delivery may require dry forms of vaccines whose powder properties allow for a low cost, heat and freeze tolerance, efficient aerosolization, and the ability to target cells of the immune system. For each of these reasons, nanoparticles can play a critical role in the formulation, development and delivery of needle-less vaccination. This review aims to communicate present biomaterial design issues surrounding the incorporation of nanoparticles into pulmonary vaccines.

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  • Article: Pulmonary immunization of guinea pigs with diphtheria CRM-197 antigen as nanoparticle aggregate dry powders enhance local and systemic immune responses.
    Pavan Muttil, Brian Pulliam, Lucila Garcia-Contreras, John Kevin Fallon, Chenchen Wang, Anthony James Hickey, David A Edwards
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    ABSTRACT: This study establishes the immune response elicited in guinea pigs after pulmonary and parenteral immunizations with diphtheria CRM-197 antigen (CrmAg). Several spray-dried powders of formalin-treated/untreated CrmAg nanoaggregates with L-leucine were delivered to the lungs of guinea pigs. A control group consisting of alum with adsorbed CrmAg in saline was administered by intramuscular injection. Animals received three doses of powder vaccines containing 20 or 40 μg of CrmAg. The serum IgG titers were measured for 16 weeks after the initial immunization; IgA titers were measured at the time of sacrifice in the broncho-alveolar lavage fluid. Further, toxin neutralization tests in naïve guinea pigs were performed for a few select serum samples. Histopathology of the lung tissues was conducted to evaluate inflammation or injury to the lung tissues. While the highest titer of serum IgG antibody was observed in guinea pigs immunized by the intramuscular route, those animals immunized with dry powder formulation by the pulmonary route, and without the adjuvant alum, exhibited high IgA titers. A pulmonary administered dry powder, compared to parenteral immunization, conferred complete protection in the toxin neutralization test. Mild inflammation was observed in lung tissues of animals receiving dry powder vaccines by the pulmonary route. Thus, administering novel CrmAg as dry powders to the lungs may be able to overcome some of the disadvantages observed with the existing diphtheria vaccine which is administered by the parenteral route. In addition, these powders will have the advantage of eliciting a high mucosal immune response in the lungs without using traditional adjuvants.
    The AAPS Journal 09/2010; 12(4):699-707. · 5.09 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

critical role
 
efficient aerosolization
 
immune system
 
low cost
 
nanoparticles
 
needle-less vaccination
 
present biomaterial design issues
 
pulmonary delivery
 
pulmonary vaccines
 
reasons
 
target cells
 
vaccines
 

Brian Pulliam