School of Life Sciences, Northwest University, Xi'an, 710069, People's Republic of China.
Biomed Phys Eng Express. 2020 Jun 18;6(4):045020. doi: 10.1088/2057-1976/ab9ab2.
Some diseases could be treated by Tanshinone IIA (TA), which is an isolated component from the Chinese medicinal herb Tanshen (Salvia miltiorrhiza). However, the poor water solubility and low oral bioavailability of TA limited its clinical application. In this paper, TA was encapsulated by water - soluble chitosan/poly - γ - glutamic acid (WCS-γ-PGA) to improve its dissolution and oral bioavailability. The in vitro dissolution and in vivo metabolism of the encapsulated composite in rats were employed to evaluate the efficiency of the improvement. FTIR spectroscopy was applied to confirm the validity of encapsulation for TA by WCS-γ-PGA. The study's results showed that the optimal ratio of TA to drug carrier (WCS + γ-PGA) was 1:5.5 in weight with a reaction time of 1 h at room temperature for the encapsulation. The proper concentrations for WCS and TA in preparing the encapsulated composite using γ-PGA 0.125 mg ml were 6 mg ml and 1 mg ml, respectively; The encapsulation efficiency and drug loading efficiency of WCS-γ-PGA-TA composite were (93.99 ± 2.20)% and (10.73 ± 0.75)%, respectively. The cumulative release of TA from the WCS-γ-PGA-TA encapsulated composite reached to 81% within 60 min, which was 5.56 times of that of the original TA in vitro dissolution. The peak concentration C of TA from the encapsulated composite in rat blood as measured by an ultracentrifugation test of an intra - gastric administration was 4.43 times that of the original TA concentration, and the area under the drug-time curve AUC and AUC (p<0.01) of the WCS-γ-PGA-TA encapsulated composite were 4.56 and 4.20 times that of the original TA, respectively. It indicated that the encapsulation of TA with WCS-γ-PGA improved its solubility and bioavailability significantly.
一些疾病可以用丹参酮 IIA（TA）治疗，它是一种从中药丹参（Salvia miltiorrhiza）中分离出来的成分。然而，TA 的水溶性差和口服生物利用度低限制了其临床应用。本文采用水溶性壳聚糖/聚-γ-谷氨酸（WCS-γ-PGA）包封 TA，以提高其溶解度和口服生物利用度。采用大鼠体内外溶出度和代谢试验评价其改良效果。傅里叶变换红外光谱（FTIR）用于确认 WCS-γ-PGA 包封 TA 的有效性。研究结果表明，TA 与药物载体（WCS+γ-PGA）的最佳重量比为 1:5.5，室温下反应 1 小时。用 0.125mg/mlγ-PGA 制备包封复合物时，WCS 和 TA 的最佳浓度分别为 6mg/ml 和 1mg/ml；WCS-γ-PGA-TA 复合物的包封率和载药量分别为（93.99±2.20）%和（10.73±0.75）%。WCS-γ-PGA-TA 包封复合物在 60min 内的累积释放量达到 81%，是原 TA 体外溶出度的 5.56 倍。胃内给药后超速离心试验测定大鼠血中 TA 的峰浓度 C 是原 TA 浓度的 4.43 倍，WCS-γ-PGA-TA 包封复合物的药时曲线下面积 AUC 和 AUC （p<0.01）分别是原 TA 的 4.56 倍和 4.20 倍。结果表明，WCS-γ-PGA 包封 TA 可显著提高其溶解度和生物利用度。
