Preparation, statistical optimization, in vitro characterization, and in vivo pharmacological evaluation of solid lipid nanoparticles encapsulating propolis flavonoids: a novel treatment for skin edema

Propolis is a natural resinous product and exerts anti-inflammatory properties. The aim of this study is formulation and characterization of solid lipid nanoparticles (SLNs) encapsulating propolis flavonoids (PFs), intended for topical treatment of skin edema. The nanoparticles were prepared and statistically optimized using Box-Behnken response surface methodology. The in vitro release profile of the optimized nanoparticles was investigated. Cytotoxicity of nanoparticles on HSF-PI 18 cell line was determined. Permeation and penetration of nanoparticles across the incised skin were measured. Finally, the nanoparticles were incorporated into a pharmaceutical hydrogel formulation and the in vivo efficacy in reduction of skin edema was determined. The size, PdI, zeta potential, entrapment efficiency (EE%) and loading efficiency (LE %) of the optimized nanoparticles were 111.3 ± 19.35 nm, 0.34 ± 0.005, -24.17 ± 3.3 mV, 73.5 ± 0.86%, and 3.2 ± 0.27%, respectively. Data obtained through in vitro release study suggested a burst release followed by a prolonged release behavior up to 24 h post incubation time interval. The prepared SLNs exhibited no cytotoxicity on HSF-PI 18 cell line. Ex vivo permeation and penetration study of nanoparticles across the incised skin showed approximately a 2.5-fold and a 3-fold increase in cumulative amount of transport and cumulative amount of skin penetration, respectively. Finally, in vivo studies in rat models, showed a threefold reduction in volume of the edema in animals treated with SLNs. The obtained data revealed that the prepared SNs entrapping PFs, exert high skin targeting effects, prolonged anti-inflammatory properties and therefore high efficiency in treatment of skin edema.

Keywords: Box–Behnken response surface methodology; Propolis flavonoids; skin penetration; skin permeation; solid lipid nanoparticles (SLNs); topical anti-inflammatory properties.