Encapsulation of Valproate-Loaded Hydrogel Nanoparticles in Intact Human Erythrocytes: A Novel Nano-cell Composite for Drug Delivery

Abstract

A novel drug delivery system possessing prolonged release behavior is introduced to the field of carrier erythrocytes and nanotechnology-based drug delivery. Encapsulation of valproate-loaded nanogels inside human erythrocytes as a novel nanocell composite was the objective of the study to obtain a model novel drug delivery system with an intravenous sustained drug delivery characteristic. "Ionotropic gelation" was used for the fabrication of hydrogel nanoparticles. The nanoparticles obtained were evaluated in vitro (particle size, transmitting electron microscopy, zeta potential, Fourier transform infrared spectroscopy, etc.). "Hypotonic dialysis" was used to obtain nanoparticle-loaded erythrocytes. Finally, in vitro characterization tests were performed on nanoparticle-loaded erythrocytes. Number- and volume-based sizes, loaded amount (mg), loading ratio (%), and loading efficiency (%) of nanoparticles were, respectively, 61 ± 2 and 74 ± 2 nm, 20.6 ± 1.02 mg, 31.58 ± 1.86%, and 6.86 ± 0.41%. Spherical structure and slightly negative zeta potential of nanoparticles were confirmed. Erythrocytes were loaded by valproate-loaded nanoparticles (entrapment efficiency of 42.07 ± 3.6%). Carrier erythrocytes showed acceptable properties in vitro and demonstrated a prolonged drug release behavior over 3 weeks. This approach opens new horizons beyond the current applications of carrier erythrocytes for future investigations.