title: Optimization of the process variables of tilianin-loaded composite phospholipid liposomes based on response surface-central composite design and pharmacokinetic study.
abstract: Tilianin is attracting considerable attention because of its antihypertensive, anti-atherogenic and anticonvulsive efficacy. However, tilianin has poor oral bioavailability. Thus, to improve the oral bioavailability of tilianin, composite phospholipid liposomes were adopted in this work as a novel nanoformulation. The aim was to develop and formulate tilianin composite phospholipid liposomes (TCPLs) through ethanol injection and to apply the response surface-central composite design to optimize the tilianin composite phospholipid liposome formulation. The independent variables were the amount of phospholipids (X1), amount of cholesterol (X2) and weight ratio of phospholipid to drug (X3); the depended variables were particle size (Y1) and encapsulation efficiency (EE) (Y2) of TCPLs. Results indicated that the optimum preparation conditions were as follows: phospholipid amount, 500 mg, cholesterol amount, 50mg and phospholipid/drug ratio, 25. These variables were also the major contributing variables for particle size (101.4 ± 6.1 nm), higher EE (90.28% ± 1.36%), zeta potential (-18.3 ± 2.6 mV) and PDI (0.122 ± 0.027). Subsequently, differential scanning calorimetry techniques were used to investigate the molecular interaction in TCPLs, and the in vitro drug release of tilianin and TCPLs was investigated by the second method of dissolution in the Chinese Pharmacopoeia (Edition 2015). Furthermore, pharmacokinetics in Sprague Dawley rats was evaluated using a rat jugular vein intubation tube. Results demonstrated that the Cmax of TCPLs became 5.7 times higher than that of tilianin solution and that the area under the curve of TCPLs became about 4.6-fold higher than that of tilianin solution. Overall, our results suggested that the prepared tilianin composite phospholipid liposome formulations could be used to improve the bioavailability of tilianin after oral administration.
authors.affiliation: Institute of Traditional Chinese Medicine, Xinjiang Medical University, Urumqi 830054, PR China; Xinjiang Institute of Materia Medica, Urumqi 830004, PR China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Zeng
authors.affiliation: Department of pharmacy, The Sixth Affiliated Hospital of Xinjiang Medical University, Urumqi 830002, PR China.
authors.forename: Wen
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Xinjiang Institute of Materia Medica, Urumqi 830004, PR China.
authors.forename: Meie
authors.initials: M
authors.lastname: Tan
authors.affiliation: Xinjiang Institute of Materia Medica, Urumqi 830004, PR China.
authors.forename: Xiaoyi
authors.initials: X
authors.lastname: Yang
authors.affiliation: Xinjiang Institute of Materia Medica, Urumqi 830004, PR China.
authors.forename: Chenghui
authors.initials: C
authors.lastname: He
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of Pharmaceutics, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China. Electronic address: huangwei@imm.ac.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.affiliation: Xinjiang Institute of Materia Medica, Urumqi 830004, PR China. Electronic address: xjguodd@163.com.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Xing
mesh_terms: D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning / Q000379:methods; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002784:Cholesterol / Q000378:metabolism; D065546:Drug Liberation; D005419:Flavonoids / Q000737:chemistry* / Q000493:pharmacokinetics*; D006027:Glycosides / Q000737:chemistry* / Q000493:pharmacokinetics*; D008081:Liposomes / Q000737:chemistry* / Q000493:pharmacokinetics*; D008297:Male; D010316:Particle Size; D010743:Phospholipids / Q000737:chemistry* / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D005419:Flavonoids; D006027:Glycosides; D008081:Liposomes; D010743:Phospholipids; C426884:tilianin; D002784:Cholesterol
keywords: Cholesterol (PubChem CID: 5997); Composite phospholipid liposomes; In vitro drug release; Lecithin Hydrogenated (PubChem CID: 10,147,142); Pharmacokinetic; Phosphatidylcholine (PubChem CID: 45,266,626); Response surface-central composite design; Tilianin; Tilianin (PubChem CID: 5,321,954)