Synthesis, optimization, physicochemical characterization, and in vitro evaluation of Solid Lipid Nanoparticles for the improved delivery of Polyphenols across a phospholipid bilayer model

Abstract

Polyphenols are one of the most common phytochemicals, with a high relevance on human diet due to its wide presence on edible plants. Particularly, quercetin and curcumin stands out for its beneficial bioactivities, mostly related to their antioxidant and anti-inflammatory effects. However, its therapeutical potential is not fully exploited due to their low bioavailability and poor water solubility, being rapidly excreted from the body or metabolized. To overcome those drawbacks, the objective of this research project is to evaluate and optimize the incorporation of those compounds into nanoparticle formulations. For those purposes, Solid Lipid Nanoparticles (SLN) made of Cetyl palmitate and Tween® 80 were synthetized. The optimization process allowed synthetize quercetin- or curcumin-loaded SLN with diameter and size below 200 nm and 0.2, respectively, which in first instance allows the system to be a suitable candidate for delivery applications. SLN zeta-potential of loaded SLN was also measured, with -3.5756 ± 0.6577 and -4.1089 ± 0.5921 mV for quercetin- and curcumin-loaded SLN, respectively. Next, a Multilamellar Vesicle (MLV) model from 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and cholesterol were synthetized to mimic the properties of the cellular lipid membrane and to calculate the delivery efficiency of quercetin and curcumin-loaded SLN, giving a respective 16 and 81%. Finally, the safety of the SLN system was addressed by means of cytotoxicity assays on HDFA cells, which showed no inhibition of cell viability among all the unloaded SLN treatments, with a maximum of 14.51 mg/mL. Quercetin- and curcumin-loaded SLN showed cytotoxicity at 150 and 245 μM, respectively. The system showed proper physicochemical characteristics suitable for delivery applications, and its proved safety allows to perform further research focused on a specific target tissues and diseases.