Abstract |
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.
|
Authors | Yan-Li Hao, Ying-Jie Deng, Yan Chen, Ke-Zhan Wang, Ai-Jun Hao, Yong Zhang |
Journal | The Journal of pharmacy and pharmacology
(J Pharm Pharmacol)
Vol. 57
Issue 10
Pg. 1279-87
(Oct 2005)
ISSN: 0022-3573 [Print] England |
PMID | 16259756
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Antineoplastic Agents
- Liposomes
- Polyethylene Glycols
- Topotecan
|
Topics |
- 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)
|