Development and evaluation of prototype microneedle vaccine formulations against COVID-19

COVID-19 infection and related disorders affect both the patient and the whole world in terms of health, economy, social and psychological aspects. Since the beginning of the pandemic, there have been approximately 7 million deaths and 800 million cases. Ensuring herd immunity is very important for this infection. Many vaccine platforms have been developed for this purpose. However, the rapid mutation of variants and the ineffectiveness of vaccines developed against newly formed variants pose a great risk. Therefore, there is an urgent need to develop effective vaccine platforms against this infection. Polymeric nanoparticles help prevent the degradation of the antigen in the body in vaccines, thus prolonging the residence time of the antigen in the body and providing a longer immune response. In addition to being used in the formulation as a carrier, they have the ability to increase the effect of the immune response by acting as an adjuvant. Therefore, it is an interesting carrier system. In our study, polymeric nanoparticles were produced by solvent evaporation method using FDA approved PEG-b-PCL (polyethyleneglycol-block-poly(ε-caprolactone)) polymer. In nanoparticle formulation, firstly, preformulation studies were carried out using model protein. In the prepared nanoparticle formulations, parameters such as % concentration and amount of inner and outer phase, sonication time and power, mixing time were changed and the appropriate formula was selected by considering the encapsulation efficiency and particle size properties of the formulations. Then, the same characterization studies were carried out by loading the RBD antigen into this formula. Vaccine application with microneedles has been one of the interesting topics recently. This interest is increasing due to the high rate of immune cells in the skin, the fact that microneedles allow painless application due to their structure, the need for healthcare personnel is eliminated thanks to the possibility of self-administration, and there is no need for cold chain application. A dissolving microneedle formulation was developed in the thesis study because it leaves no residue after application, it is not possible to re-application after application, and thus reduces the risk of contamination. While developing the microneedle formulation, the best results were selected among the formulas with suitable morphology and hardness, and characterization studies were carried out. Our results show that the nanoparticle formulations are properly loaded with antigen and that the microneedles have sufficient strength and morphology to pierce the skin.