(T1430-02-13) Roles of Protein Corona in Physicochemical Properties and Stability of pH-Triggering Self-Assembled Nanoparticles of Drug-Myristic Acid Conjugate

Purpose: To investigate the effect of human serum albumin as a protein corona on the physicochemical properties and stability of self-assembled drug-myristic acid conjugate nanoparticles (QMN).

Methods: QMN was obtained from drug-myristic acid conjugate (QMC) by pH-triggered self-assembly method at pH 1.2 without surfactants. The adsorption of albumin on QMN was performed by drop-wisely adding 1 mL QMN (50 mg/mL) to 10 mL albumin solution in phosphate-buffered saline 0.01 M (PBS), pH 7.4 (20 mg/mL) under the stirring condition (1000 rpm) at room temperature. The amount of QMC and hard corona albumin in the albumin-coated QMN was quantitatively determined by HPLC-UV method and bicinchoninic acid assay, respectively. Physicochemical properties and stability of QMN and albumin-coated QMN were characterized. Drug release in PBS containing 0.5% tween 80 using a dialysis method and cell viability tests in mouse myoblast cells (C2C12) were also performed for albumin-coated QMN in comparison with the bare QMN.

Results: The albumin adsorption on the spherical QMN surface increased particle size from around 180 to 220 nm as a function of time and protein concentration, along with a surface charge reversal from approximately +60 to -16 mV. Quantitatively, hard corona albumin accounted for about 10% (w/w) of the albumin-coated QMN. Albumin was adsorbed on the surface of QMN initially by electrostatic force and later by hydrophobic interaction via the conformation change of albumin confirmed by fluorescent and circular dichroism spectra. The albumin-coated QMN remained stable in different ionic strength (0.005-0.5 M) and in both FBS/PBS 10% and FBS over 96 h at 37^oC, while QMN was aggregated in low ionic strength (0.005 M NaCl) and serum protein conditions. Albumin-coated QMN improved the drug release profile with a sustained release of around 45% QMC in one month and showed no toxicity to myoblast cells.

Conclusion: The pre-formation of protein corona on the surface of QMN using albumin could modify the physicochemical properties (particle size and surface charge), resulting in the improved stability, drug release and biocompatibility of QMN for a potential long-acting drug delivery system.

Acknowledgements: Supported by a grant from the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (RS-2023-00208240), Republic of Korea.