以不同嵌段比例mPEG-PLA为载体制备番茄红素胶束及其对番茄红素各异构体的增溶控释作用研究

Preparation of Lycopene Micelles with Different Block Ratios of mPEG-PLA as Carriers and the Solubilization and Controlled Release

以三种不同嵌段比例的聚乙二醇单甲醚-聚乳酸(mPEG-PLA)共聚物为载体,通过乳化-溶剂挥发法制备了番茄红素胶束(M-LYC),采用高效液相色谱法(HPLC)测定M-LYC中番茄红素(LYC)各异构体的含量,计算其包封率(EE)和载药量(DL),采用动态光散射纳米粒径分析仪测定粒径及Zeta电位,并通过透析法测定M-LYC在不同释放介质中的体外释放度,以筛选包载LYC的最佳嵌段比例的mPEG-PLA共聚物。结果表明,mPEG_(45)-PLA_(36)-M-LYC、mPEG_(114)-PLA_(90)-M-LYC、mPEG_(114)-PLA_(180)-M-LYC中总LYC的EE分别为65.04%、71.73%、23.62%,DL分别为3.96%、4.43%、1.39%,粒径分别为164.6、190.1、210.3 nm,Zeta电位分别为-15.38、-9.43、-10.96 mV。mPEG_(114)-PLA_(90)-M-LYC中各异构体及总LYC的EE最高,其次为mPEG_(45)-PLA_(36)-M-LYC,三种胶束中各顺式异构体包封率大小顺序均为5Z>9Z>13Z;mPEG_(45)-PLA_(36)-M-LYC在三种胶束中粒径最小且Zeta电位绝对值最大,说明其稳定性最好。LYC原料在不同释放介质中均未检测到LYC释放出来,三种胶束中,mPEG_(45)-PLA_(36)-MLYC的总LYC在不同释放介质中72 h累积释放百分率均最高,分别为42.35%(pH6.8)和60.82%(pH7.4);三种胶束在pH7.4释放介质中的累积释放百分率均高于pH6.8;三种胶束中全反式番茄红素(All-E)72 h累积释放百分率比总LYC略高,5Z在初期无释放,经过72 h后累积释放百分率高于All-E。综上所述,mPEG_(45)-PLA_(36)对LYC的包载效果较佳,以其为载体制备的M-LYC在三种胶束中粒径最小、Zeta电位绝对值最大、稳定性最好,且72 h总LYC的累积释放百分率最高,是一种极具潜力的包载LYC的高分子聚合物载体材料,并有望提高脂溶性营养物质在体内的生物利用度。

By applying three different block ratios of polyethylene glycol monomethyl ether-polylactic acid(mPEG-PLA)copolymers as carriers,the lycopene micelles(M-LYC)were created by emulsification-solvent evaporation method.The content of each isomer of lycopene(LYC)in M-LYC was determined by high performance liquid chromatography(HPLC),and the encapsulation rate(EE)and drug loading capacity(DL)of micelles were calculated.To screen the mPEG-PLA copolymers for the ideal block ratio of encapsulating LYC,the particle size and zeta potential were evaluated using a dynamic light scattering nano-particle size analyzer,and the in vitro release of M-LYC in different release media was assessed using dialysis method.The results showed that the EE of Total LYC in mPEG45-PLA36-M-LYC,mPEG114-PLA90-M-LYC,and mPEG114-PLA180-M-LYC were 65.04%,71.73%and 23.62%,respectively,with DL of 3.96%,4.43%and 1.39%,particle sizes of 164.6,190.1 and 210.3 nm,and zeta potential of−15.38,−9.43 and−10.96 mV,respectively.The EE of each isomer and Total-LYC in mPEG114-PLA90-M-LYC was the highest,followed by mPEG45-PLA36-M-LYC.The order of encapsulation rate of each cis-isomer in the three micelles was 5Z>9Z>13Z.The mPEG45-PLA36-M-LYC had the smallest particle size and the largest absolute value of zeta potential among the three micelles,indicating that it had the best stability.The release of LYC in LYC feedstock was not detected in different release media.Among the three micelles,the mPEG45-PLA36-M-LYC had the highest cumulative release percentage of Total LYC within 72 h in different release media,with 42.35%(pH6.8)and 60.82%(pH7.4),respectively.The cumulative release percentages of all three micelles in the pH7.4 release medium were higher than those in the pH6.8 condition,and the cumulative release percentages of all-trans lycopene(All-E)were slightly higher than those of Total LYC within 72 h.5Z had the higher cumulative release percentages than All-E after 72 h,with no initial release.In conclusion,the mPEG45-PLA36 has a better effect on the encapsulation of LYC than other copolymers.The M-LYC prepared with its carrier has the smallest particle size,the largest absolute zeta potential,the best stability and the highest cumulative release percentage of 72 h Total LYC among the three micelles,which is a promising polymeric carrier material for encapsulating LYC and is expected to improve the in vivo bioavailability of fat-soluble nutrients.