目的 通過(guò)調(diào)節(jié)納米骨架載藥系統(tǒng)（NDDS）中載體類型和比例實(shí)現(xiàn)對(duì)纈沙坦體外溶出和體內(nèi)生物利用度的調(diào)控。方法 以纈沙坦作為模型藥物，分別選取酸性敏感材料Eudragit E100（E100）、堿性敏感材料Eudragit L100-55（L100-55）作為載體材料，介孔二氧化硅Sylysia 350（S350）、Aerosil 200（A200）作為納米骨架，通過(guò)調(diào)節(jié)載體和骨架材料的類型和比例篩選出具有pH 1.2、6.8敏感釋放行為的納米骨架載體處方，考察纈沙坦在pH 1.2、6.8環(huán)境中釋放和在大鼠體內(nèi)的藥動(dòng)學(xué)行為特征。結(jié)果 篩選的pH 1.2敏感釋放纈沙坦NDDS處方纈沙坦、S350、E100比例為1∶3∶1，pH 6.8敏感釋放纈沙坦NDDS處方為纈沙坦、A200、L100-55比例為1∶1∶3。pH 6.8敏感釋放處方可調(diào)控纈沙坦在腸道pH 6.8條件下特異性溶出；pH 1.2敏感釋放處方在保持纈沙坦在pH 6.8高溶出特性的同時(shí)可特異性地提高胃部酸性條件下的藥物釋放。pH 1.2、6.8敏感釋放纈沙坦NDDS均一定程度上改善了纈沙坦的生物利用度，其中pH 6.8敏感釋放纈沙坦NDDS提高生物利用度的幅度更高，血藥濃度變化比較平緩。結(jié)論 NDDS可以調(diào)控纈沙坦的體外溶出和生物利用度，有望應(yīng)用于pH值敏感性難溶藥物的遞送。

Objective To control in vitro dissolution and in vivo bioavailability of valsartan (Val) by adjusting the carrier type and ratio in nano-matrix drug delivery system (NDDS). Methods Valsartan was used as the model drug, acid-sensitive material Eudragit E100 (E100) and alkali-sensitive material Eudragit L100-55 were selected as carrier materials, and mesoporous silica Sylysia 350 (S350) and Aerosil 200 were used as nano-framework. The nano-framework carrier formulations with pH 1.2 and 6.8 sensitive release behavior were screened out in different proportions, and the release of valsartan in pH 1.2 and 6.8 environment and the pharmacokinetic behavior characteristics in rats were investigated. Results The ratio of Val, S350, and E100 in the NDDS formulation of pH 1.2 sensitive release valsartan was 1:3:1, and the ratio of Val, A200, and L100-55 in the NDDS formulation of pH 6.8 sensitive release valsartan was 1:1:3. The pH 6.8 sensitive release formulation can control the specific dissolution of valsartan at pH 6.8 in the intestinal tract, and the pH 1.2 sensitive release formulation can specifically improve the dissolution rate of valsartan under the acidic gastric condition while maintaining the high dissolution characteristics of valsartan release at pH 6.8. Both pH 1.2 and 6.8 sensitive release valsartan NDDS improved the bioavailability of valsartan to a certain extent. Among them, pH 6.8 sensitive release valsartan NDDS improved the bioavailability more, and the blood concentration changed more gently. Conclusion NDDS can regulate the in vitro dissolution and bioavailability of valsartan, which is expected to be applied to the delivery of pH-sensitive insoluble drugs.

R927.1

國(guó)家重大科學(xué)研究計(jì)劃項(xiàng)目(2015CB932100)