Preparation, characterization and in-vitro anti-cholestatic activity of swertiamarin-loaded galactosylated solid lipid nanoparticle

Background: Cholestatic liver injury (CLI) is a rapidly progressive liver disorder characterized by the accumulation of bile acids (BA). The therapeutic effects of current medicines used to treat CLI are unsatisfactory. Objectives: This study aimed to prepare galactosylated solid lipid nanoparticle (SLN) with swertiamarin (STM) by using a galactosylated lipid, N-hexadecyl lactobionamide (N-HLBA) and evaluate its anti-cholestasis effect in-vitro. Methods: The galactosyl-lipid N-HLBA was prepared via the lactone form intermediates of lactobionic acid and synthesized by anchoring galactose to hexadecylamine lipid. The STM-loaded galactosylated SLN (STM-GalSLN) was successfully prepared by a melt-emulsification-ultrasound method. The prescription was optimized by orthogonal test. The morphology was observed by transmission electron microscope. The particle size and zeta potential were determined by laser granularity equipment. The encapsulation efficiency (EE) and drug loading capacity (DL) were determined by ultrafiltration, centrifugation and HPLC method. Results: The optimized prescription was as follows: 50 mg of STM, 20 mg of N-HLBA, 500 mg of glyceryl behenate, 400 mg of soybean lecithin, 200 mg of poloxamer188 and 500 mg of Tween 80. The STM-GalSLN was spherical in shape and its particle size, zeta potential, EE and DL were 164.40±4.68 nm, -14.53±3.20 mV, 82.41±2.88 % and 0.32±0.02 %, respectively, and the EE of STM-GalSLN did not change significantly over 30 days at 4°C. Furthermore, STM-GalSLN alleviated cholestatic liver injury (CLI) in a concentration-dependent manner in-vitro. Conclusion: The findings from this study indicated that the melt-emulsification-ultrasound method was rational and reliable, which provided an experimental basis for developing a new nano preparation of STM for CLI.