Phospholipid/zein hybrid nanoparticles as promising carriers for the protection and delivery of all-trans retinoic acid

Highlights: • Zein and phospholipids were used to obtain hybrid nanosystems. • These hybrid nanosystems increased the photo-stability of all-trans retinoic acid (ATRA). • The addition of mannose and glucose promoted the long-term storage of the hybrid nanoparticles. • The hybrid nanosystems preserved the in vitro antitumor activity of ATRA. A totally biodegradable mixed system made up of phospholipids and zein was developed in order to effectively improve the photostability of all-trans retinoic acid (ATRA) preserving its pharmacological properties. Photon correlation spectroscopy showed that the formulation obtained using phospholipon 85G and zein at a ratio of 7:3 w/w was characterized by an average diameter of less than 200 nm, a narrow size distribution and a significant time- and temperature-dependent stability. The use of specific cryoprotectants such as mannose and glucose favoured the long-term storage of the nanocarriers after the freeze-drying procedure. The nanoparticles increased the stability of the ATRA against photochemical degradation with respect to the free drug and its antitumor effect was preserved as a consequence of the cell uptake of the colloidal systems. The results demonstrate the potential of the proposed hybrid nanosystems to provide a high level of stabilization for sensitive and labile antitumor compounds.