Preparation of gastrodin multivesicular liposomes based on microfluidic technology and evaluation of brain targeting
Objective Micro fluidic technology was used to prepare Gastrodin(GAS)multivesicular liposomes(GAS-MVLs),and to investigate the pharmacokinetic and brain targeting properties of GAS-MVLs in mice.Methods Using the formability as the evaluation index,a single-factor experiment was conducted to select the GAS-MVLs forming process;using the encapsulation rate as the index,the orthogonal experiment was conducted to optimize the GAS-MVLs formula with the variables of the ratio of GAS to lecithin,the ratio of cholesterol to lecithin,the ratio of lecithin to triolein,and the concentration of polyoxyethylene sorbitan monolaurate.The GAS-MVLs were characterized by encapsulation rate,particle size,polymer dispersion index(PDI),and morphology,and the in vitro cumulative release rate and initial stability were tested.The GAS concentration in the plasma and brain tissue of mice given GAS or GAS-MVLs(30 mg·kg-1)at 5,15,30,60,90,120,150,180,240,and 300 min was determined by HPLC,and the brain targeting of GAS-MVLs was evaluated by relative uptake rate(Re),targeting efficiency(Te)and peak concentration ratio(Ce).Results The optimized formula was a ratio of GAS to lecithin of 1∶2,a ratio of cholesterol to lecithin of∶:1,a ratio of lecithin to triolein of 1∶2,and a concentration of polyoxyethylene sorbitan monolaurate of 6％.The egg yolk was prepared by dissolving the specified amount of lecithin,cholesterol,and triolein in a chloroform-ethanol(2∶1)mixture as the lipid phase,and dissolving GAS in water as the internal aqueous phase.The internal aqueous phase was added to the lipid phase in a ratio of 2:3,and the mixture was sonicated for 3 minutes in an ice bath to form an emulsion.The external aqueous phase was prepared by adding 6％polyoxyethylene sorbitan monolaurate as the aqueous phase,and the emulsion and the external aqueous phase were injected from different inlets into a micro,by using a Y-type chip,the total volumetric flow rate(18.78 mL·h-1)and the volume flow ratio(external aqueous phase∶colloidal dispersion=23∶1)were set,and the organic solvent was removed by nitrogen,resulting in GAS-MVLs.The average particle size of GAS-MVLs was(2.09±0.14)μm,the PDI was(0.258±0.013),and the average encapsulation rate was(34.47±0.39)％.The distribution was uniform,the morphology was round and compact,and the structure was dense.GAS dissolved rapidly in the release medium,and the release amount after 6 hours was close to 90％.In the stability test,the average particle size of GAS-MVLs slowly increased,and the encapsulation rate slowly decreased.In the pharmacokinetics test,Re was 5.70,Te was 0.37,and Ce was 2.04.Conclusion The preparation of GAS-MVLs by microfluidic technology can significantly improve the degree of intracerebral enrichment of GAS,which lays the foundation for further development of GAS brain-targeted formulations.
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