Tunable assembly of mixed PLGA-lipid nanoparticles via monoolein with improved reactive oxygen species cell protection

Oxidative stress leads to pathologies such as photodamaged skin, psoriasis, and hyperpigmentation. Polymeric nanoparticles based on Poly-lactic-co-glicolic acid (PLGA) containing Idebenone improve its penetration into target skin cells reducing the level of free radicals. Despite these advantages, the lack of knowledge of endogenous barriers hinders the design of nanoparcticles. To address this problem, hybrid polymeric nanoparcticles with lipid components can improve stability and cellular internalization, increasing the antioxidant amount inside the cell. In this work, we designed and tested new mixed nanoformulations based on PLGA to deliver Idebenone using two lipid stabilizers as Monoolein (MO) and 2-distearoyl-sn-glycero-3-phosphoethanol-amine-polyethylene glycol-2000 (DSPE-PEG2000). Atomic Force Microscopy and Dynamic Light Scattering noted the crucial role of the monoolein concentration in defining the size and the shape of the nanoparcticles. Small-angle X-ray Scattering and Molecular Dynamics simulations evidenced the interactions between monoolein and Idebenone to lead to a homogeneous arrangement at the nanoscale. The Electron Paramagnetic Resonance together with Density Functional Theory confirmed protection rate of nanoformulations against OH. radicals. Cytotoxicity and flow cytometry confirmed that nanoparcticles with high and low monoolein concentrations scavenge reactive oxygen species (ROS) with greater efficacy than Idebenone alone. This scavenging ability indicates that the presence of nanoparcticles enhances the Idebenone’s adsorption and cell protection from oxidative stress.