title: A lyophilized sterically stabilized liposome-containing docetaxel: in vitro and in vivo evaluation.
abstract: OBJECTIVE
  In this study, an improved lyophilized PEGylated liposomal formulation of docetaxel (DOC) has been developed.
  
  
  METHODS
  PEGylated docetaxel liposome (PL-DOC) was prepared by thin-film evaporation method and lyophilization. The effect of various components of the lipids and their compatibility with DOC on the entrapment efficiency (EE) of liposome was investigated. The lyophilized PL-DOC was characterized by morphology, particle size, zeta potential, EE, release in vitro and stability. Pharmacokinetics and biodistribution in vivo of lyophilized PL-DOC were also investigated.
  
  
  RESULTS
  The optimal liposome formulation was egg phosphatidylcholine (EPC):cholesterol (CH):DSPE-PEG2000:DOC = 56:40:4:4 (molar ratio). Sucrose and mannitol were chosen as cryoprotectant in the lyophilization (cryoprotectant-to-lipid (C/L) mass ratio  = 8:1). The size of lyophilized PL-DOC was 152.3 ± 1.0 nm with negative charge and the EE was 89.75 ± 1.79%. Compared with nonlyophilized PL-DOC, the lyophilized PL-DOC was more stable at 4 °C for six months. The lyophilized PL-DOC also showed the good stability after reconstituted by 5% glucose injection. In vitro release study of PL-DOC showed that PL-DOC had a sustained release effect. After i.v. administration at the dose of 10 mg/kg in rats, a significant increase in the AUC0-∞, MRT0-∞and t1/2was observed in PL-DOC group compared with conventional docetaxel liposome (CL-DOC) and DOC injection (DOC-I) group. Biodistribution studies in mice showed that PL-DOC significantly decreased the uptake by the organs of mononuclear phagocytic system (MPS), such as liver and spleen, while prolonging the retention time of DOC in the plasma.
  
  
  CONCLUSIONS
  Our PEGylated liposome formulation reported in this study could potentially produce viable clinical strategies for improved delivery of DOC for the treatment of human cancer.
authors.affiliation: a School of Chinese Materia Medica, Guangzhou University of Chinese Medicine , Guangzhou , China.
authors.forename: Yuchao
authors.initials: Y
authors.lastname: Chen
authors.affiliation: a School of Chinese Materia Medica, Guangzhou University of Chinese Medicine , Guangzhou , China.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: a School of Chinese Materia Medica, Guangzhou University of Chinese Medicine , Guangzhou , China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: a School of Chinese Materia Medica, Guangzhou University of Chinese Medicine , Guangzhou , China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Luo
authors.affiliation: a School of Chinese Materia Medica, Guangzhou University of Chinese Medicine , Guangzhou , China.
authors.forename: Pinjing
authors.initials: P
authors.lastname: Zheng
authors.affiliation: a School of Chinese Materia Medica, Guangzhou University of Chinese Medicine , Guangzhou , China.
authors.forename: Yidan
authors.initials: Y
authors.lastname: Tong
authors.affiliation: a School of Chinese Materia Medica, Guangzhou University of Chinese Medicine , Guangzhou , China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Li
mesh_terms: D000818:Animals; D000077143:Docetaxel; D008081:Liposomes / Q000032:analysis / Q000493:pharmacokinetics; D051379:Mice; D008815:Mice, Inbred Strains; D051381:Rats; D017207:Rats, Sprague-Dawley; D043823:Taxoids / Q000032:analysis / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D008081:Liposomes; D043823:Taxoids; D000077143:Docetaxel
keywords: Biodistribution; PEGylated; lyophilization; pharmacokinetic; stability