title: Preparation, characterization, pharmacokinetics and tissue distribution of solid lipid nanoparticles loaded with tetrandrine.
abstract: Tetrandrine (TET) is a poorly water-soluble bisbenzylisoquinoline alkaloid. In this study, TET solid lipid nanoparticles (SLNs) were prepared by a melt-emulsification and ultrasonication technique. Precirol(®) ATO 5, glyceryl monostearate, and stearic acid were used as the lipid matrix for the SLNs, while Lipoid E80, Pluronic F68, and sodium deoxycholate were used as emulsifying and stabilizing agents. The physicochemical characteristics of the TET-SLNs were investigated when it was found that the mean particle size and zeta potential of the TET-SLNs were 134 ± 1.3 nm and -53.8 ± 1.7 mV, respectively, and the entrapment efficiency (EE) was 89.57% ± 0.39%. Differential scanning calorimetry indicated that TET was in an amorphous state in SLNs. TET-SLNs exhibited a higher release rate at a lower pH and a lower release rate at a higher pH. The release pattern of the TET-SLNs followed the Weibull model. The pharmacokinetics of TET-SLNs after intravenous administration to male rats was studied. TET-SLN resulted in a higher plasma concentration and lower clearance. The biodistribution study indicated that TET-SLN showed a high uptake in reticuloendothelial system organs. In conclusion, TET-SLNs with a small particle size, and high EE, can be produced by the method described in this study. The SLN system is a promising approach for the intravenous delivery of tetrandrine.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, People's Republic of China.
authors.forename: Su
authors.initials: S
authors.lastname: Li
authors.forename: Zhaoshuai
authors.initials: Z
authors.lastname: Ji
authors.forename: Meijuan
authors.initials: M
authors.lastname: Zou
authors.forename: Xin
authors.initials: X
authors.lastname: Nie
authors.forename: Yijie
authors.initials: Y
authors.lastname: Shi
authors.forename: Gang
authors.initials: G
authors.lastname: Cheng
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000493:pharmacokinetics; D044182:Benzylisoquinolines / Q000008:administration & dosage / Q000493:pharmacokinetics; D002152:Calorimetry, Differential Scanning / Q000379:methods; D003840:Deoxycholic Acid / Q000737:chemistry; D004075:Diglycerides / Q000737:chemistry; D045703:Emulsifying Agents / Q000737:chemistry; D005079:Excipients / Q000737:chemistry; D005989:Glycerides / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007275:Injections, Intravenous; D008055:Lipids / Q000008:administration & dosage / Q000737:chemistry; D008297:Male; D051379:Mice; D046529:Microscopy, Electron, Transmission / Q000379:methods; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D020442:Poloxamer / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D013229:Stearic Acids / Q000737:chemistry; D014018:Tissue Distribution; D014465:Ultrasonics / Q000379:methods
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D044182:Benzylisoquinolines; D004075:Diglycerides; D045703:Emulsifying Agents; D005079:Excipients; D005989:Glycerides; D008055:Lipids; D013229:Stearic Acids; D003840:Deoxycholic Acid; D020442:Poloxamer; C048159:glyceryl monostearate; C009438:tetrandrine; C031183:stearic acid; C009032:precirol