Preparation And Evaluation Of GA-BSA Microparticles

Objective As one of the main active ingredients in Glycyrrhiza uralensis Fisch, Glycyrrhetinic acid(GA) has been proven to be effective for the treatment of various liver diseases. However, GA is poorly soluble in water and its short biological half-time presents obstacles for its clinical efficacy. Based on the existing disadvantages of GA, the aim of the present study was to prepare the Glycyrrhetinic acid-Bovine serum albumin(GA-BSA) microparticle with an appropriate size, high drug encapsulation and drug loading capacity, sustained-release and liver-targeted properties.Method The formulation of GA nanosuspension was optimized based on particle size and preliminary stability. Using GA nanosuspension and GA-BSA nanoparticles as material respectively, the GA-BSA microparticle was prepared and the process method was optimized. The influence of different stabilizers, BSA concentration and crosslinkers amount were systematically investigated based on particle size distribution, drug loading capacity and drug encapsulation. The formulation was optimized by single factor test. The surface morphology of the microparticles was observed by transmission electron microscopy(TEM). The crystalline state of GA in different samples was investigated by X-ray powder diffraction analysis(XRD). The potential interaction between GA and BSA was assessed using a FTIR spectrophotometer and Differential scanning calorimetry(DSC). In vitro dissolution study was also studied to explore the mechanism of drug release. The tissue distribution in mice was carried out to research the liver-targeted properties of GA-BSA microparticles.Result The optimized GA nanosuspension formulation was obtained while TPGS-SDS was chosen as the composite stabilizer and PVP K30 as steric stabilizer and prepared by a simple anti-solvent precipitation method. The GA nanosuspensions with a quite small particle size(54 nm, PDI=0.370) and a good storage stability.The obtained GA-BSA nanosuspensions were further assembled into microparticles using zinc chloride as ionic crosslinker and glutaraldehyde as covalent crosslinker. When the concentration of BSA is 7.5 mg/mL, the amount of 25 % zinc chloride and 0.1 % glutaraldehyde is 10 ?L/mg BSA and 4 ?L/mg BSA, respectively. The obtained GA-BSA microparticles displayed a reasonable EE of(75.0 ± 2.36) % and DL of(30.2 ± 1.18) % and with an approximate size of 2 ?m. In vitro dissolution study demonstrated a typical sustained-release pattern for 24 h with a burst of 28.1 % at the first 0.5 h, which fitted well by Higuchi model. DSC, XRD and FTIR spectrophotometer suggested that GA was highly embedded and dispersed in the BSA matrix.The tissue distribution after intravenous administration into mice indicated that, the microparticle formulation remained a higher drug level than the solution formulation in blood and liver for more than 18 h, showed a significant liver-targeting capability.Conclusion The GA-BSA microparticles were obtained by a simple anti-solvent precipitation followed by cross-linked method exhibited as spherical particles with size about 2 ?m, high encapsulation efficiency and drug loading capacity, sustained-release behavior and liver-targeted properties. These results indicated that the potential benefit of using the prepared albumin microparticles as a promising delivery model for enhanced bioavailability of poorly water-soluble drug.