Flame-Made Fractal-Like Inorganic Nanoaggregates as Drug Carriers

Biologics (proteins, peptides, nucleotides) dominate the novel therapeutics market. A major obstacle in their employment, however, is their enzymatic degradation and poor stability in vivo demanding high doses that result in side-effects. 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 [1-3].<br/><br/>To produce the nanocarriers, we employ flame spray pyrolysis, a technique which allows tuning of NPs properties like composition, size, crystallinity. Most importantly, the as-produced nanoparticles self-assemble into larger sub-micron aggregates with a characteristic fractal-like morphology. These parameters are critical as they determine the mode of cellular uptake. We optimize the loading of CaP nanoaggreates with biologics and other organic molecules. The performance of the developed particles is benchmarked with the state-of-the-art assays.<br/><br/>We have synthesized amorphous CaP and SiO₂ nanpoaggregates with varying silica content totune hydrodynamic size, biologic loading capacity, and cell cytotoxicity. We obtain a high specific surface area of greater 200 m²/g for all these NPs. Upon loading model biological drugs and polyphenols, we achieved high loading capacity values when compared to the literature. None of these particles showed cytotoxicity on human lung epithelial cells.<br/><br/>As a conclusion, the flame-made nanoaggrates developed on this study exhibit advantageous properties for their employment in drug delivery with high loading values and minimal cytotoxicity.<br/><br/>References<br/>[1] V. Tsikourkitoudi, J. Karlsson, P. Merkl, E. Loh, B. Henriques-Normark & <b><u>G. A. Sotiriou</u></b>*. “Flame-made calcium phosphate nanoparticles with high drug loading for delivery of biologics” <b>Molecules </b>25, 1747 (2020).<br/>[2] <b><u>G. A. Sotiriou</u></b>, C. O. Blattmann & Y. Deligiannakis*. “Nanoantioxidant-driven plasmon enhanced proton-coupled electron transfer” <b>Nanoscale</b> 8, 796-803 (2016).<br/>[3] Y. Deligiannakis*, <b><u>G. A. Sotiriou</u></b> & S. E. Pratsinis. “Antioxidant and antiradical SiO2 nanoparticles covalently functionalized with gallic acid” <b>ACS Applied Materials & Interfaces</b> 4, 6609-6617 (2012).