Phospholipid complex as an approach for bioavailability enhancement of echinacoside
Phospholipid complex as an approach for bioavailability enhancement of echinacoside
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DOI：
10.3109/03639045.2015.1004183
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发表时间：
2015-11-02
影响因子：
3.4
通讯作者：
Zhang, Chunfeng
中科院分区：
文献类型：
--
作者：
Li, Fei;Yang, Xiaolin;Zhang, Chunfeng
内容：松果菊苷（Echinacoside，ECH）具有多种药理活性，但口服ECH吸收差，生物利用度低，不能发挥其治疗作用。因此，迫切需要开发一种新的口服剂型，以增强其肠道吸收，提高生物利用度。目的：将ECH制成磷脂复合物（phytosome，PHY）来增强ECH在体内的肠吸收和口服生物利用度。采用溶剂挥发法制备了PHY，并通过差示扫描量热法（DSC）和红外光谱（IR）对其进行了表征，结果：正辛醇/水分配系数（P）的测定结果表明，与物理混合物（MIX）和ECH相比，PHY的形成显著增强了ECH的亲脂性。因此，肠吸收率（K-a）提高到2.82倍，有效渗透系数（P-eff）增加到3.39倍。采用高效液相色谱法测定大鼠口服PHY后不同时间血浆中ECH的浓度。大鼠体内的药动学参数分别为Tmax =1.500h、Cmax =3.170mg/mL、AUC（0-infinity）=9.375mg/Lh、AUC（0-24）=7.712mg/Lh。
Context: Echinacoside (ECH) has been shown to possess a multitude of pharmacological activities, however, oral administered ECH failed to fulfill its therapeutic potential due to poor absorption and low bioavailability. Thus, there is a pressing need to develop a new oral dosage form to enhance its intestinal absorption and improve bioavailability.Objective: The aim of this study was to formulate ECH into phospholipid complex (phytosome, PHY) to enhance intestinal absorption and oral bioavailability of ECH in vivo.Methods: The PHY was prepared by a solvent evaporation method and was characterized by differential scanning calorimetry (DSC) and infrared spectroscopy (IR), and then the physicochemical properties, intestinal absorption and bioavailability of the PHY were investigated.Results: Compared with the physical mixture (MIX) or ECH alone, the n-octanol/water partition coefficient (P) determination results showed that the lipophilicity of ECH was significantly enhanced by formation of PHY. Accordingly, the intestinal absorption rate (K-a) was improved to 2.82-fold and the effective permeability coefficient (P-eff) increased to 3.39-fold. The concentrations of ECH in rat plasma at different times after oral administration of PHY were determined by HPLC. Pharmacokinetic parameters of the PHY in rats were T-max=1.500h, C-max=3.170mg/mL, AUC(0-infinity)=9.375mg/Lh and AUC(0-24)=7.712mg/Lh, respectively.Conclusions: Compared with ECH alone or the MIX group, the relative bioavailability of ECH was increased significantly after formulation into PHY (p