title: Pegylated liposomal mitoxantrone is more therapeutically active than mitoxantrone in L1210 ascitic tumor and exhibits dose-dependent activity saturation effect.
abstract: Our previous studies have proved that encapsulation of mitoxantrone into pegylated SUVs (plm60-s) could enhance its antineoplastic efficacy (Li et al., 2008b). However, why plm60-s is more therapeutically active than free mitoxantrone (MIT), and whether pharmacokinetics and activity of plm60-s exhibits dose-dependency are left unknown. In studies with L1210 ascitic tumor-bearing mice in which the dose of MIT was elevated from 2 to 8mg/kg, a saturation of antineoplastic efficacy was observed after plm60-s, and not after free MIT therapy. Total MIT concentrations in plasma, liver and ascitic fluids after plm60-s increased linearly with escalated doses. The released MIT concentrations in ascitic fluid increased continuously before reaching the peak at a dose of 6mg/kg and then decreased. In vitro release experiments using ascitic fluid as release medium revealed that at high concentrations of plm60-s the release of drug was inhibited. At a dose of 4mg/kg, the areas under the curve (AUC) of released MIT in ascitic fluid after plm60-s were higher than those after free MIT, which might be responsible for the enhanced efficacy of plm60-s. These observations may be used to choose a dose regimen of plm60-s to ensure optimal efficacy and to expound the reasons why plm60-s was more therapeutically active.
authors.affiliation: School of Pharmacy, Hebei Medical University, Shijiazhuang, PR China; CSPC ZhongQi Pharmaceutical Technology (Shijiazhuang) Co., Ltd, Shijiazhuang, PR China; Hebei Pharmaceutical Engineering & Technology Research Center, Shijiazhuang, PR China; State Key Lab of Novel Pharmaceutical Preparations and Excipients, Shijiazhuang, PR China. Electronic address: lcllib@hotmail.com.
authors.forename: Chunlei
authors.initials: C
authors.lastname: Li
authors.affiliation: CSPC ZhongQi Pharmaceutical Technology (Shijiazhuang) Co., Ltd, Shijiazhuang, PR China; Hebei Pharmaceutical Engineering & Technology Research Center, Shijiazhuang, PR China; State Key Lab of Novel Pharmaceutical Preparations and Excipients, Shijiazhuang, PR China.
authors.forename: Xi
authors.initials: X
authors.lastname: Zhao
authors.affiliation: CSPC ZhongQi Pharmaceutical Technology (Shijiazhuang) Co., Ltd, Shijiazhuang, PR China; Hebei Pharmaceutical Engineering & Technology Research Center, Shijiazhuang, PR China; State Key Lab of Novel Pharmaceutical Preparations and Excipients, Shijiazhuang, PR China.
authors.forename: Chenxin
authors.initials: C
authors.lastname: Deng
authors.affiliation: CSPC ZhongQi Pharmaceutical Technology (Shijiazhuang) Co., Ltd, Shijiazhuang, PR China; Hebei Pharmaceutical Engineering & Technology Research Center, Shijiazhuang, PR China; State Key Lab of Novel Pharmaceutical Preparations and Excipients, Shijiazhuang, PR China.
authors.forename: Caixia
authors.initials: C
authors.lastname: Wang
authors.affiliation: CSPC ZhongQi Pharmaceutical Technology (Shijiazhuang) Co., Ltd, Shijiazhuang, PR China; Hebei Pharmaceutical Engineering & Technology Research Center, Shijiazhuang, PR China; State Key Lab of Novel Pharmaceutical Preparations and Excipients, Shijiazhuang, PR China.
authors.forename: Na
authors.initials: N
authors.lastname: Wei
authors.affiliation: School of Pharmacy, Hebei Medical University, Shijiazhuang, PR China. Electronic address: cjxlib@hotmail.com.
authors.forename: Jingxia
authors.initials: J
authors.lastname: Cui
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D001202:Ascitic Fluid / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007939:Leukemia L1210 / Q000188:drug therapy* / Q000378:metabolism; D008081:Liposomes; D008297:Male; D051379:Mice; D008942:Mitoxantrone / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; D011092:Polyethylene Glycols; D008942:Mitoxantrone
keywords: Biodistribution; Dose dependency; Efficacy; Mitoxantrone; Pegylated liposomes; Pharmacokinetics