Development of Oral Influenza Vaccine Delivery System Utilizing pH Responsive Pored Microparticles

• Author / Creator

  Kumar, Ankit

• Influenza is a major respiratory disease caused by influenza virus. Recent spread of the extremely pathogenic avian and swine influenza viruses paint a morbid picture of the emergence of a more lethal influenza virus in future. Currently, hypodermic needles are being dominantly employed in vaccination worldwide. However, inherent limitations such as the need for highly skilled healthcare workers, high cost (production and administration), and safety concerns over needle reuse render it undesirable in developing nations. As an alternative, solid oral vaccines have emerged as a promising platform due to potential advantages like generation of both mucosal and systemic humoral immune responses, no biohazardous waste (i.e., needles), no prerequisite for cold supply chain for transportation/storage, convenient stockpiling due to solid formulation, long shelf life, and the ability to self-administer. Despite these potential advantages of oral vaccines, they are still elusive to commercialization due to their instability in the gastric environment. Our research goal is to develop a novel oral vaccine delivery vehicle, which can sense pH change of the environment. To this end, we successfully fabricated a Microparticle-based vaccine delivery system, which can protect and release vaccines in response to different pH environments of the stomach and small intestine, respectively. In this research, comprehensive methodology to fabricate microparticles has been reported. As a systematic approach, concept testing was performed to identify any potential design problems or challenges associated with MPs prior to their incorporation of real vaccine. Briefly, MPs were synthesized in oil-in-water (O/W) emulsion method using Poly (methyl methacrylate) (PMAA)-based Food and Drug Administration (FDA) approved anionic copolymer. Combined effects of temperature and solvent composition/evaporation conditions on MPs characteristics were investigated to find key process parameters to make optimally functioning pH-responsive MPs. Morphological change of the MPs was shown to be important to maintain high level of antigenic stability from in vitro experiments using model drugs (100 nm polystyrene nanoparticles and sulforhodamine b). Morphology and size of MPs were examined with scanning electron microscopy (SEM) and dynamic light scattering (DLS) at gastric/intestine pH conditions. Quantitative analysis of the loading efficiency and time dependent release profile of model drugs were performed using a plate reader and fluorescence microscope. Furthermore, for detailed surface characterization of MPs, FTIR, NMR and DSC analysis were performed. Although these efforts were majorly aimed at the demonstration of concept in vitro, this work is expected to contribute to development of a universal platform for oral vaccines.

• Subjects / Keywords

  • Microparticles
  • Oral Vaccine
  • Advanced Drug Delivery
  • Influenza

• Graduation date

  Fall 2015

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/R3GQ6RG9F

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.