Silymarin is the main constituent of the extract from seeds of Silybum marianum L. Gaertn. and has been used for decades as hepatoprotectant. Recently it has been proposed to be beneficial in type 2 diabetes patients. However, silymarin is a poorly water soluble drug with limited oral bioavailability [1]. Nanoparticles-based delivery systems resulted a promising strategy to resolve these issues. In this work, nanostructured lipid carriers (NLCs) with two different lipid combinations were prepared through emulsion/evaporation/solidifying method [2]. Stearic acid:Capryol 90 (NLCs-SA) and cetyl palmitate:Lauroglycol 90 (NLCs-CP) were selected as lipid mixtures. Brij S20 was used as surfactant. The optimized formulations were of 210-270 nm in particle size and with zeta potential between -31 and -35 mV. Surface morphology was determined by TEM. NLCs showed good encapsulation efficiencies (80% for NLCs-SA and 93% for NLCs-CP). No degradation phenomena were observed in simulated gastrointestinal fluids. Storage stability of suspensions and lyophilized products was also investigated. Glucose and mannitol were selected as cryoprotectant agents for freeze drying and it was observed that glucose was superior to mannitol especially with regard to the physical stability. About 60% of silymarin was released in 24 h in PBS. Invitropermeation experiments with artificial membranes and Caco-2 cells revealed that both NLCs enhanced the permeation of entrapped compound. Cellular uptake studies indicated that active processes are involved in the internalization of developed formulations.
Acknowledgments:Financial support was granted by Ente Cassa di Risparmio di Firenze 2016, financing n. 2016.0802.
References:
[1] Bilia AR, et al. Improving on Nature: The Role of Nanomedicine in the Development of Clinical Natural Drugs. Planta Med 2017; 83: 366-381.
[2] Graverini G, Piazzini V, et al . Solid lipid nanoparticles for delivery of andrographolide across the blood-brain barrier: in vitro and in vivo evaluation. Colloid Surf B Biointerfaces 2018; 161: 302-313.