目的 研究β-环糊精(β-CD)、羟丙基-β-环糊精(HP-β-CD)和磺丁基醚-β-环糊精(SBE-β-CD)对姜黄素离体角膜渗透作用的影响.方法 采用改良Franz扩散池,以离体角膜扩散实验考察不同质量分数的3种环糊精对姜黄素角膜渗透性的影响.结果 β-CD质量分数为0.02%、0.04%、0.06%、0.08%时,姜黄素的角膜表观渗透系数分别增加了1.06、1.03、1.00、0.95倍,同质量分数的HP-β-CD分别增加了1.16、1.19、1.17、1.12倍,质量分数为0.04%、0.06%时,与对照组相比有显著差异(P< 0.05);同质量分数的SBE-β-CD分别增加了1.06、1.23、1.08、0.90倍,质量分数为0.04%时,与对照组相比有显著差异(P< 0.05).以质量分数为0.06%的SBE-β-CD作为促渗剂,姜黄素释放曲线符合零级释放方程(r=0.997 8);角膜水化平均为81.7%.结论 HP-β-CD质量分数为0.04%、0.06%,分别增加表观渗透系数1.19、1.17倍(P< 0.05);SBE-β-CD为0.04%时,增加1.23倍(P< 0.05).SBE-β-CD作为眼用促渗剂使药物的释放过程更加安全有效;3种环糊精促渗剂对角膜无刺激.

Objective To study the effects of β-cyclodextrin (β-CD), hydroxypropyl-β-CD (HP-β-CD), and sulfobutyl-ether-β-CD (SBE-β-CD) on in vitro corneal penetration of curcumin. Methods Improved Franz-cells were used for the corneal diffusion test and the cumulative permeation quantity of curcumin in the corneal was determined by HPLC. Results β-CD at 0.02%, 0.04%, 0.06%, and 0.08% improved the apparent permeability coefficient as much as 1.06, 1.03, 1.00, and 0.95 times. HP-β-CD at 0.02%, 0.04%, 0.06%, and 0.08% improved the apparent permeability coefficient as much as 1.16, 1.19, 1.17, and 1.12 times; HP-β-CD at 0.04% and 0.06% there was a significant deference compared with the control group (P < 0.05). SBE-β-CD at 0.02%, 0.04%, 0.06%, and 0.08% improved apparently the permeability coefficient as much as 1.06, 1.23, 1.08, and 0.90 times. SBE-β-CD at 0.04% there was a significant deference compared with the control group (P < 0.05). SBE-β-CD at 0.06% as penetration enhancer, release curve accorded with zero order release equation (r = 0.997 8). The average of the corneal hydration is 81.7%. Conclusion HP-β-CD at 0.04% and 0.06% could improve the apparent permeability coefficient as much as 1.19 and 1.17 times (P < 0.05). SBE-β-CD at 0.04% could improve the apparent permeability coefficient as much as 1.23 times (P < 0.05). SBE-β-CD as corneal penetration enhancers can release safely and effectively. As corneal penetration enhancers, those three kinds of cyclodextrin are without irritation to corneal.

国家自然科学基金资助项目(81303142);高等学校博士学科点专项科研基金项目(20121210120001);天津市应用基础与前沿技术研究计划(14JCQNJC13100)