2024 AIChE Annual Meeting

(489a) Flame-Made Fractal-like Nanoparticles As Drug Carriers

Author

Sotiriou, G. A. - Presenter, Karolinska Institutet
Biologics (proteins, peptides, nucleotides) dominate the novel therapeutics market. A major obstacle in their employment, however, is their enzymatic degradation in vivo demanding high doses that result in side-effects [1,2]. One way to avoid degradation of biologics is to encapsulate them in nanocarriers, such as lipid-based nanoparticles. An alternative approach is to use biocompatible inorganic nanoparticles, such as calcium phosphate (CaP). CaP nanoparticles have been explored as drug nanocarriers for biologics and as adjuvants in nanovaccines. In this study, we aim to improve the drug loading capacities of biologics by utilizing inorganic CaP nanoaggregates made by flame aerosol technology, with fractal-like morphology and high specific surface area [3]. We use flame spray pyrolysis, a technique which allows tuning of NPs properties like composition, size, crystallinity. These parameters are critical as they determine the mode of cellular uptake. We optimize the loading of CaP nanoaggreates with biologics, targeting two distinct applications: as antimicrobial peptide delivery carriers and as adjuvants for vaccination. The performance of the developed particles is benchmarked with the state-of-the-art lipid-based nanoparticles for biologic drug delivery.We have synthesized amorphous CaP NPs with varying silica content totune hydrodynamic size, biologic loading capacity, and cell cytotoxicity. We obtain a high specific surface area of greater 150 m2/g for all these NPs. Upon loading ovalbumin, a model protein antigen, we achieved loading capacity values of up to 400 μg/mg NPs. None of these particles showed cytotoxicity on human lung epithelial cells. We further use ovalbumin loaded CaP NPs as a model system to optimize the antigen uptake and tune the inflammatory response by immune cells. The flame-made CaP nanoaggrates developed on this study exhibit advantageous properties for their employment in biologics delivery with high loading values and minimal cytotoxicity.

References

[1] Pati, R., et al. (2018). Frontiers in immunology, 9, 2224.

[2] Lin, Y., et al (2017). Expert review of vaccines, 16(9), 895-906.

[3] Tsikourkitoudi, V., et al. (2020) Molecules, 25(7), 1747.