In-vitro cytotoxicity, in-vivo biodistribution and anti-tumour effect of PEGylated liposomal topotecan.

In attempt to increase the accumulation of topotecan in tumours and improve its anti-cancer activity, PEGylated liposome (H-PEG) containing topotecan was prepared. The in-vitro cytotoxicity, in-vivo biodistribution pattern and anti-tumour effect of H-PEG were studied systemically. Compared with free topotecan or conventional liposome (H-Lip), H-PEG improved the cytotoxic effect of topotecan against human ovarian carcinoma A2780 and human colon carcinoma HCT-8 cells. The IC50 value (concentration leading to 50% cell-killing) of H-PEG decreased 5 fold (P<0.01) and 9 fold (P<0.01) against A2780 and HCT-8 cells compared with H-Lip, respectively. The results of biodistribution studies in sarcoma S(180) tumour-bearing mice showed that liposomal encapsulation increased the concentration of total topotecan and the ratio of lactone form in plasma. H-PEG resulted in a 70-fold and 3.7-fold increase in AUC(0-->24 h) compared with free topotecan and H-Lip, respectively. Moreover, H-PEG increased the accumulation of topotecan in tumours and the relative tumour uptake ratio compared with free topotecan was 5.2, and higher than that of H-Lip. The anti-cancer effect studies in murine heptocarcinoma H(22) tumour-bearing mice showed that H-PEG improved the therapeutic efficiency of topotecan and decreased the toxicity of topotecan to a certain extent compared with H-Lip. These results indicated that PEG-modified liposome might be an efficient carrier of topotecan.
AuthorsYan-Li Hao, Ying-Jie Deng, Yan Chen, Ke-Zhan Wang, Ai-Jun Hao, Yong Zhang
JournalThe Journal of pharmacy and pharmacology (J Pharm Pharmacol) Vol. 57 Issue 10 Pg. 1279-87 (Oct 2005) ISSN: 0022-3573 [Print] England
PMID16259756 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antineoplastic Agents
  • Liposomes
  • Polyethylene Glycols
  • Topotecan
  • Animals
  • Antineoplastic Agents (pharmacokinetics, pharmacology, therapeutic use)
  • Area Under Curve
  • Biological Availability
  • Bone Marrow (chemistry, drug effects, metabolism)
  • Cell Line, Tumor
  • Cell Survival (drug effects)
  • Drug Compounding (methods)
  • Drug Stability
  • Female
  • Humans
  • Inhibitory Concentration 50
  • Liposomes (chemistry, pharmacokinetics)
  • Liver (drug effects, metabolism)
  • Lung (chemistry, drug effects, metabolism)
  • Male
  • Mice
  • Mice, Inbred ICR
  • Neoplasms, Experimental (drug therapy, metabolism)
  • Polyethylene Glycols (chemistry, pharmacokinetics)
  • Spleen (drug effects, metabolism)
  • Tissue Distribution (drug effects)
  • Topotecan (chemistry, pharmacokinetics, pharmacology)
  • Xenograft Model Antitumor Assays (methods)

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