Novel Delivery Systems for Nasal Adminstration of Anthrax Vaccine
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Wang, Sheena Hailin. Novel Delivery Systems for Nasal Adminstration of Anthrax Vaccine. 2010. https://doi.org/10.17615/18xs-cz14APA
Wang, S. (2010). Novel Delivery Systems for Nasal Adminstration of Anthrax Vaccine. https://doi.org/10.17615/18xs-cz14Chicago
Wang, Sheena Hailin. 2010. Novel Delivery Systems for Nasal Adminstration of Anthrax Vaccine. https://doi.org/10.17615/18xs-cz14- Last Modified
- March 22, 2019
- Creator
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Wang, Sheena Hailin
- Affiliation: Eshelman School of Pharmacy, Division of Pharmacoengineering and Molecular Pharmaceutics
- Abstract
- There is current biodefense interest in protection against Anthrax. The inhaled form of anthrax is difficult to diagnose and can be fatal without prompt antibiotic intervention. Prophylactic vaccination has become a critical measure for protection of individuals at risk of exposure. This thesis makes the efforts to develop a new generation of stable, effective and affordable anthrax vaccine. This project studies the immune response elicited by rPA with a mast cell activator, Compound 48/80 as adjuvant. The vaccine formulation was prepared in a dry powder form by spray-freeze-drying (SFD) under optimized conditions to produce particles with a target size of 25[mu]m median diameter, suitable for rabbit nasal delivery. Physicochemical properties of the powder vaccines were characterized in order to assess the powder delivery and storage potentials. Structural stability of PA after the SFD process and storage were confirmed by two spectroscopic techniques (CD and ATR-FTIR), while functional stability of both the antigen and adjuvant were monitored via cell-based assays. Animal studies were performed to evaluate the in vivo efficacy of the powder vaccines rabbits using a Unitdose powder device. Results showed that C48/80 is an effective mucosal adjuvant in rabbits. SFD powder formulations freshly prepared or stored for over two years at room temperature were able to elicit a significant serum anti-body and functional titer comparable to IM injection. An in-situ formed hydrogel delivery was proposed as a compliment to the moisture sensitive dry powder formulation, which would offer flexibility in terms of dosing. The hydrogel precursor, a small peptide derivative, was prepared and purified. In vitro experiments demonstrated hydrogel formation in the presence of reconstituted powder formulation. Rheology studies showed instant hydrogel formation and in vivo mucoadhesive behavior is expected given successful enzymatic conversion. In vitro release studies have shown that the formulation is suitable for nasal delivery of soluble antigen rPA. Powder hydrogel combined formulation is feasible as nasal product. Initial animal study has been conducted, yet future work is needed to identify optimal conditions for the hydrogel-powder combined formulation.
- Date of publication
- August 2010
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- In Copyright
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- ... in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Division of Molecular Pharmaceutics.
- Advisor
- Hickey, Anthony J.
- Degree granting institution
- University of North Carolina at Chapel Hill
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