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Formulation of adjuvanted PLGA nanoparticles for pandemic influenza vaccine delivery

ContributorsMarmy, Aurélie
Master program titleMaster en Pharmacie
Defense date2020-12-25
Abstract

An Influenza gets to the pandemic stage when caused by a new viral strain against which the human population has little or no immunity and thus becomes a global outbreak that can last multiple months or years. This new strain can be harmless or deadly and could target any type of population. A pandemic always leads to important economic losses and intensive utilization of some key economic sectors such as health or food supply, as observed during the pandemic caused by Sars-CoV-2 virus. Several things must be set in place in order to prepare for an eventual pandemic flu, research for vaccine as well as its commercialization and access has a key role in this regard. Researches are, currently, being carried out on H5N1 virus strain, known to be one of the deadliest. Studies showed that a large antigen dose or multiple doses had to be administered in order to guarantee protection, though the ideal would be to be in possession of a vaccine that can be efficient in a single shot in case of a pandemic. In order to increase the efficiency level of a vaccine, combining it with adjuvants is one of the possibilities as those directly increase the immune system response. Those adjuvants can be immunostimulants interacting with the immune system or vehicles helping to present the antigen or other substances to the immune system cells such as antigens presenting cells (APCs). The aim of this project was to formulate PLGA nanoparticles (NPs) containing a combination of two immunostimulant adjuvants, a saponin and a NOD2 receptor agonist. Two saponins were investigated being tomatine and solanine, and one NOD2 receptor ligand, SG101. First of all, nanoprecipitation method used, in order to create empty PLGA NPs, was optimized. Centrifugation parameters were determined in order to obtain a better yield: 24’000 rpm style, 4 °C temperature, 10 minutes duration and 2 mL tube’s volume. Sucrose at a 2 % concentration was chosen as cryoprotectant for the freeze-drying stage. Then, saponins were encapsulated through three methods: Nanoprecipitation, microfluidics and simple emulsion. Formulations with and without cholesterol were tested. Simple emulsion was assessed as the method of choice for tomatine’s encapsulation. A hemolytic toxicity test was carried out to evaluate the hemolytic activity of both solanine and tomatine. Tomatine turned out to be more toxic than solanine. The addition of cholesterol in the formulation removed tomatine’s hemolytic activity and probably this would apply for solanine. Selected samples allowed to show a stability of PLGA NPs after a 6 to 10 weeks storage at 4 °C after freeze drying. To conclude, single or combined immunostimulants were successfully formulated in PLGA NPs. However, it will be necessary to optimize formulation in order to increase the active small drugs concentrations in PLGA NPs and to be able to further test the in vitro and in vivo activities of formulated adjuvanted PLGA NPs.

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Citation (ISO format)
MARMY, Aurélie. Formulation of adjuvanted PLGA nanoparticles for pandemic influenza vaccine delivery. 2020.
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Master thesis
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  • PID : unige:160450
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