ABSTRACT
OBJECTIVE To prepare and characterize curcumin nanomicelles （hereinafter referred to as Cur/mPEG-PBLA micelles）， and to evaluate the in vitro hepatoprotective activity against alcohol liver disease （ALD）. METHODS Cur/mPEG-PBLA micelles were prepared with the dialysis method using methoxy-poly（ethylene glycol）-poly（β-benzyl-L-aspartate） （mPEG-PLGA） as the carrier. The appearance and microscopic morphology of Cur/mPEG-PBLA micelles were observed， and particle size， polydispersity index， Zeta potential， encapsulation efficiency and drug loading content were all detected. The in vitro release， pH stability， thermal stability， dilution stability， storage stability， plasma stability tests， and hemolysis experiments were all performed. The cell model of ALD was established with anhydrous ethanol intervention using human liver cancer cells and normal liver cells as objects， Cur reference solution as reference， to evaluate in vitro preventive and ameliorative effects of Cur/mPEG- PBLA micelles on ALD. RESULTS The prepared Cur/mPEG-PBLA micelles exhibited a pale-yellow milky light， with a spherical shape and uniform distribution. The average particle size was about 140 nm， and the polydispersity index was less than 0.3. Zeta potential was （－8.15±0.05） mV； the encapsulation efficiency was （73.26±3.16）%， and the drug loading content was （4.87± 0.42）%. The cumulative release of Cur reference substance was close to 80% at 10 h； the cumulative release of Cur/mPEG-PBLA micelles at 8 h was 28.94% and only 48.25% at 48 h. pH stability and thermal stability of Cur/mPEG-PBLA micelles were better than those of Cur reference solution； Cur/mPEG-PBLA micelles showed good dilution stability， storage stability and plasma stability， and would not cause hemolysis. Cur reference solution and Cur/mPEG-PBLA micelles had varying degrees of in vitro preventive and ameliorative effects on ALD in two types of cells； after 48 h of application， the above effects of Cur/mPEG-PBLA micelles were significantly better than those of Cur reference solution at the same mass concentration （P＜0.05）. CONCLUSIONS Cur/mPEG-PBLA micelles can improve pH stability and thermal stability of Cur， delayits degradation rate， and have better in vitro hepatoprotective activity against ALD.
ABSTRACT
Objective To design and synthesize a different molecular mass block copolymer of poly(L-phenylalanine)-b-poly (L-aspartic acid)(PPA-PAA). Methods The L-phenylalanine and L-aspartic acid were used as raw materials to synthesize L-phenyl?alanine N-carboxy-ɑ-amino acid anhydride and L-aspartic acid-β-benzylester N-carboxy-ɑ-amino acid anhydride. The target com?pounds of amphiphilic block copolymer of PPA-PAA were synthesized by ring-opening polymerization. The critical micelle concentra?tion of the amphiphilic polymer was determined by pyrene fluorescence probe method. Results The copolymers of hydrophobic chain segment 500,2000,and 4000 were synthesized and the structures were confirmed by hydrogen nuclear magnetic resonance and Fouri?er transformed infrared. The critical micelle concentration of polymers changed with adjusting the feed ratio of PPA to PAA. Conclu?sion The results show that the longer the hydrophobic chain segment of PPA is,the smaller the critical micelle concentration of poly?mers. The results lay the groundwork for further studying the stabilizing effect of the drug polymer nanoparticles with different proper?ties.