Preparation and in vivo pharmacokinetics of polyethylene glycol-modified myricitrin solid lipid nanoparticles
AIM To prepare polyethylene glycol-modified myricitrin solid lipid nanoparticles,and to investigate their in vivo pharmacokinetics.METHODS High-pressure homogenization method was adopted in the preparation of polyethylene glycol-modified solid lipid nanoparticles,after which the encapsulation efficiency,drug loading,particle size and Zeta potential were determined,the formulation was optimized by single factor test,the crystalline form analysis was performed by XRPD,and the in vitro drug release and stability were investigated.Twenty-four rats were randomly assigned into four groups and given intragastric administration of the 0.5%CMC-Na suspensions of myricitrin,myricitrin solid lipid nanoparticles,myricitrin solid lipid nanoparticles+polyethylene glycol stearate and polyethylene glycol-modified myricitrin solid lipid nanoparticles(150 mg/kg),respectively,after which blood collection was made at different time points,HPLC was adopted in the plasma concentration determination of myricitrin,and main pharmacokinetic parameters were calculated.RESULTS The optimal formulation was determined to be 1 ∶ 15 for drug-lipid ratio,10 ∶ 1 for glyceryl monostearate-polyethylene glycol stearate ratio,0.8%for Poloxamer 188 concentration,and 8 times for homogenization frequency,the encapsulation efficiency,drug loading,particle size,PDI and Zeta potential were 81.75%,5.04%,207.56 nm,0.092 and-14.79 mV,respectively.Myricitrin existed in the polyethylene glycol-modified solid lipid nanoparticles in an amorphous state,whose accumulative release rate was 64.71%within 18 h,along with good stability within 2 h in simulated gastric juice and within 12 h in simulated intestinal juice.Compared with raw medicine and solid lipid nanoparticles,the polyethylene glycol-modified solid lipid nanoparticles displayed prolonged tmax(P<0.05)and increased Cmax,AUC0-t,AUC0-∞(P<0.05,P<0.01),the relative bioavailability was enhanced to 4.60 times as compared with that of raw medicine.CONCLUSION Polyethylene glycol-modified solid lipid nanoparticles can improve the stability of myricetin and promote its oral absorption.
myricitrinsolid lipid nanoparticlespolyethylene glycolpreparationin vivo pharmacokineticshigh-pressure homogenization methodHPLC
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维普
