醋酸钙梯度主动载药法制备芦丁纳米脂质体

Loading rutin into nanoliposomes by forming calcium acetate gradient and its quality evaluation

目的:采用主动载药法制备芦丁纳米脂质体,提高包封率,增加药物在体外的释放。方法:利用醋酸钙梯度造成主动载药的驱动力,HPLC测定芦丁含量,离心超滤法测定脂质体包封率,激光粒度仪测定粒径分布和电位,考察单因素对包封率及粒径的影响,并进一步研究芦丁纳米脂质体在4℃的稳定性和体外释放。结果:空白脂质体10倍体积的30 g/L蔗糖、透析3次可高效建立醋酸钙梯度,20 g/L PVP作为溶解介质可有效增加芦丁的包封率和稳定性,在最佳制备工艺条件(磷脂浓度40 g/L、磷脂∶胆固醇质量比为5∶1、药脂质量比1∶30、50℃孵育15 min,包封率达80.3%)下成品脂质体平均粒径为185 nm,电位-1.2 m V,28 d稳定性良好,体外释放较完全。结论:醋酸钙梯度主动载药法可制备高包封率、释药较完全的芦丁纳米脂质体。

Aim：To prepare nanoliposomes with high entrapment efficiencies （ EE） by active loading drug method for improving absorption of rutin in the body .Methods：The gradient of calcium acetate was used to produce the driving force of loading drug .HPLC, centrifugal ultrafiltration and laser particle size analyzer were employed to determined rutin con -tent, EE, size distribution and zeta potential , respectively .The influence of various factors on the EE and size was investi-gated.Furthermore, the release behavior in vitro and stability under 4℃were studied.Results：The conditions of genera-ting calcium acetate gradient were determined as 10 volumes of 30 g/L sucrose to dialyze three times .The EE and stability of liposomes were enhanced by 20 g/L PVP solubilizing rutin .Under the optimized preparation conditions （ phospholipid con-centration 40 g/L, phospholipid：cholesterol 5：1, drug-lipid ratio 1：30, 50 ℃ incubation foe 15 min）, the EE a-chieved 80.3%.Rutin was nanosized with an average size of 185 nm, a zeta potential of -1.2 mV.Also, the preparation was stable within 28 days and more drug was released compared with native rutin .Conclusion：Active loading druy method of calcium acetate gradient can prepare rutin nanoliposomes with high EE and better release .