title: Preparation, pharmacokinetics, biodistribution, antitumor efficacy and safety of Lx2-32c-containing liposome.
abstract: Lx2-32c is a novel taxane that has been demonstrated to have robust antitumor activity against different types of tumors including several paclitaxel-resistant neoplasms. Since the delivery vehicles for taxane, which include cremophor EL, are all associated with severe toxic effects, liposome-based Lx2-32c has been developed. In the present study, the pharmacokinetics, biodistribution, antitumor efficacy and safety characteristics of liposome-based Lx2-32c were explored and compared with those of cremophor-based Lx2-32c. The results showed that liposome-based Lx2-32c displayed similar antitumor effects to cremophor-based Lx2-32c, but with significantly lower bone marrow toxicity and cardiotoxicity, especially with regard to the low ratio of hypersensitivity reaction. In comparing these two delivery modalities, targeting was superior using the Lx2-32c liposome formulation; it achieved significantly higher uptake in tumor than in bone marrow and heart. Our data thus suggested that the Lx2-32c liposome was a novel alternative formulation with comparable antitumor efficacy and a superior safety profiles to cremophor-based Lx2-32c, which might be related to the improved pharmacokinetic and biodistribution characteristics. In conclusion, the Lx2-32c liposome could be a promising alternative formulation for further development.
authors.affiliation: Key Laboratory of Molecular Pharmacology and Drug Evaluation (Ministry of Education of China), School of Pharmacy, Yantai University, Yantai, China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Wang
authors.affiliation: Key Laboratory of Molecular Pharmacology and Drug Evaluation (Ministry of Education of China), School of Pharmacy, Yantai University, Yantai, China.
authors.forename: Jianqiao
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Molecular Pharmacology and Drug Evaluation (Ministry of Education of China), School of Pharmacy, Yantai University, Yantai, China.
authors.forename: Guangyao
authors.initials: G
authors.lastname: Lv
authors.affiliation: Department of clinical medicine, Binzhou Medical College, Yantai, China.
authors.forename: Jinbo
authors.initials: J
authors.lastname: Ma
authors.affiliation: Key Laboratory of Molecular Pharmacology and Drug Evaluation (Ministry of Education of China), School of Pharmacy, Yantai University, Yantai, China.
authors.forename: Pengkai
authors.initials: P
authors.lastname: Ma
authors.affiliation: Key Laboratory of Molecular Pharmacology and Drug Evaluation (Ministry of Education of China), School of Pharmacy, Yantai University, Yantai, China.
authors.forename: Guangying
authors.initials: G
authors.lastname: Du
authors.affiliation: Key Laboratory of Molecular Pharmacology and Drug Evaluation (Ministry of Education of China), School of Pharmacy, Yantai University, Yantai, China.
authors.forename: Zongliang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Key Laboratory of Molecular Pharmacology and Drug Evaluation (Ministry of Education of China), School of Pharmacy, Yantai University, Yantai, China; State Key Laboratory of Long-acting and Targeting Drug Delivery Technologies (Luye Pharma Group Ltd.), Yantai, China.
authors.forename: Jingwei
authors.initials: J
authors.lastname: Tian
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Weishuo
authors.initials: W
authors.lastname: Fang
authors.affiliation: Key Laboratory of Molecular Pharmacology and Drug Evaluation (Ministry of Education of China), School of Pharmacy, Yantai University, Yantai, China.
authors.forename: Fenghua
authors.initials: F
authors.lastname: Fu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use* / Q000633:toxicity; D008081:Liposomes; D008297:Male; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity; D017207:Rats, Sprague-Dawley
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; C532167:Lx2-32c compound; D017239:Paclitaxel