目的 制備高載藥量、小粒徑的槲皮素納米混懸劑, 并進行性質考察。方法 采用納米沉淀-高壓均質法制備, 以粒徑分布、藥載比、穩(wěn)定性為指標對處方和工藝進行優(yōu)化, 并對最優(yōu)處方進行體外性質考察。結果 以超聲注入聯(lián)合高壓均質法制備, 最佳處方為TPGS為穩(wěn)定劑、DMF為有機試劑, 藥載比為5:1;最佳工藝條件為低溫10 ℃超聲、200 MPa、循環(huán)5次。制備得到的槲皮素納米混懸劑粒徑為(173.21±0.90) nm, 電位為(-19.02±0.15) mV, 載藥量為(80.40±1.44)%, 包封率為(96.41±1.72)%。藥物在納米粒中以結晶狀態(tài)存在, 能夠體外緩釋36 h。結論 利用TPGS可制備高載藥量、小粒徑的槲皮素納米混懸劑, 其體外具有明顯緩釋作用, 解決了槲皮素水溶性差的難題, 具有較好的應用前景。

Objective To prepare Quercetin Nanosuspensions with high drug-loading capacity and small particle size, and study their behaviors in vitro. Methods Quercetin Nanosuspensions were prepared using nano-precipitation and high-pressure homogenization method. The formulation and preparation process were optimized using particle size distribution, drug loading capacity, and stability of samples as evaluating indicators, and then the properties in vitro of optimal sample were studied. Results Ultrasonic injection and high-pressure homogenization was selected as optimal method. The optimal prescription included using TPGS as the stabilizer with the drug-stabilizer ratio of 5:1, DMF as the organic reagent. The optimal preparation was as following: ultrasonic processing was under 10 ℃, the homogenization pressure was 200 MPa, and cycles were 5 times. The prepared Quercetin Nanosuspensions had average diameter (173.21 ± 0.90) nm and Zeta potential (-19.02 ± 0.15) mV. Drug-loading content was calculated to be (80.40±1.44) % and the entrapment efficiency was determined to be (96.41±1.72)%. Quercetin was in the same form of crystalline in Quercetin Nanosuspensions as in the bulk quercetin. Quercetin could release in a sustained release manner during 36 h. Conclusion Using the polymer TPGS, Quercetin Nanosuspensions with high drug-loading and small size sustained released are prepared, and it has obviously in vitro sustained released effect, which dissolves poor water solubility of quercetin, and has good prospect of application.

國家國際科技合作專項(2008DFA31070);黑龍江中醫(yī)藥大學重點實驗室開放課題(2013kf04)