Key Laboratory of Marine Drugs of Ministry of Education, Shandong Provincial Key Laboratory of Glycoscience and Glycoengineering, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.
Marine Biomedical Research Institute of Qingdao, Qingdao 266071, China.
Int J Mol Sci. 2021 Apr 15;22(8):4077. doi: 10.3390/ijms22084077.
A self-nanoemulsifying drug delivery system (SNEDDS) was developed to enhance the absorption of heparin after oral administration, in which heparin was compounded with phospholipids to achieve better fat solubility in the form of heparin-phospholipid (HEP-Pc) complex. HEP-Pc complex was prepared using the solvent evaporation method, which increased the solubility of heparin in -octanol. The successful preparation of HEP-Pc complex was confirmed by differential scanning calorimetry (DSC), Fourier-transform infrared (FT-IR) spectroscopy, NMR, and SEM. A heparin lipid microemulsion (HEP-LM) was prepared by high-pressure homogenization and characterized. HEP-LM can enhance the absorption of heparin after oral administration, significantly prolong activated partial thromboplastin time (APTT) and thrombin time (TT) in mice, and reduce fibrinogen (FIB) content. All these outcomes indicate that HEP-LM has great potential as an oral heparin formulation.
研制了一种自微乳药物传递系统（SNEDDS）以增强肝素经口服给药后的吸收，其中肝素与磷脂复合以肝素-磷脂（HEP-Pc）复合物的形式实现更好的脂溶性。HEP-Pc 复合物采用溶剂蒸发法制备，提高了肝素在正辛醇中的溶解度。差示扫描量热法（DSC）、傅里叶变换红外（FT-IR）光谱、NMR 和 SEM 证实了 HEP-Pc 复合物的成功制备。通过高压匀质法制备了肝素脂质微乳（HEP-LM）并对其进行了表征。HEP-LM 可增强肝素经口服给药后的吸收，显著延长小鼠活化部分凝血活酶时间（APTT）和凝血酶时间（TT），并降低纤维蛋白原（FIB）含量。所有这些结果表明，HEP-LM 作为口服肝素制剂具有巨大的潜力。
