title: Liposomes with high encapsulation capacity for paclitaxel: Preparation, characterisation and in vivo anticancer effect.
abstract: Paclitaxel (PTX) is approved for the treatment of ovarian and breast cancer. The commercially available preparation of PTX, Cremophor EL(R) is associated with hypersensitivity reactions in spite of a suitable premedication. In general, the developed liposomal PTX formulations are troubled with low PTX encapsulation capacity (maximal content, 3 mol%) and accompanied by PTX crystallisation. The application of "pocket-forming" lipids significantly increased the encapsulation capacity of PTX in the liposomes up to 10 mol%. Stable lyophilised preparation of PTX (7 mol%) encapsulated in the liposomes composed of SOPC/POPG/MOPC (molar ratio, 60:20:20) doped with 5 mol% vitamin E had the size distribution of 180-190 nm (PDI, 0.1) with zeta-potential of -31 mV. Sucrose was found to be a suitable cryoprotectant at the lipid:sugar molar ratios of 1:5-1:10. This liposomal formulation did not show any evidence of toxicity in C57BL/6 mice treated with the highest doses of PTX (100 mg/kg administered as a single dose and 150 mg/kg as a cumulative dose applied in three equivalent doses in 48-h intervals). A dose-dependent anticancer effect was found in both hollow fibre implants and syngenic B16F10 melanoma mouse tumour models.
authors.affiliation: Department of Vaccinology and Immunotherapy, Veterinary Research Institute, Hudcova 70, 62100 Brno, Czech Republic.
authors.forename: Stepán
authors.initials: S
authors.lastname: Koudelka
authors.forename: Pavlína
authors.initials: P
authors.lastname: Turánek-Knötigová
authors.forename: Josef
authors.initials: J
authors.lastname: Masek
authors.forename: Zina
authors.initials: Z
authors.lastname: Korvasová
authors.forename: Michaela
authors.initials: M
authors.lastname: Skrabalová
authors.forename: Jana
authors.initials: J
authors.lastname: Plocková
authors.forename: Eliska
authors.initials: E
authors.lastname: Bartheldyová
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Turánek
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004339:Drug Compounding; D004355:Drug Stability; D005612:Freeze Drying; D008055:Lipids / Q000737:chemistry; D008081:Liposomes; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D036103:Nanotechnology; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity; D010316:Particle Size; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D008055:Lipids; D008081:Liposomes; D017239:Paclitaxel