Design and characterization of biocompatible perfluorocarbon nanodroplets for theragnostic application

We have developed stable emulsions (≥ 3 months) made of nanodroplets (nD) of perfluorocarbon (PFC) dispersed in water to serve as theragnostic agent. nD are stabilized by in house fluorinated surfactants, named FTAC, which chemical structure can be modified to tune their properties. We have characterized nD size distributions (mean diameters from 200 to 600 nm), density, adiabatic compressibility, interfacial tension. US properties of the emulsions have been investigated such as attenuation. Lastly, ultrasonic signals backscattered by nanoemulsions were studied and compared with water to extract signal to noise ratio (SNR), by emitting single negative pulses at ≈40 MHz. At similar mean/mode diameters, we showed a strong dependence in SNR values (i) with size distribution, altered by the nature of the surfactant or by a centrifugation/filtration process, (ii) with core nature, and (iii) with nD volume fraction. Besides, hydrophobic drugs such as a thalidomide derivative (with anti-angiogenic properties), have been encapsulated by addition of 10% of triacetin in the nD core. So as to study drug release from nD, a dedicated setup of US cavitation was designed. Cavitation was generated in controlled conditions using a 1 MHz focused transducer (US bursts: 12-22 MPa peak) in a thin wall container immersed in water which temperature and degassed level were kept constant. The generation of cavitation in nD solutions resulted in a strong and reproducible SNR decrease.