Abstract | PURPOSE: This study was aimed at exploring the use of liposomes to deliver aquated cisplatin (ACP), a metabolite of CDDP, with increased potency and toxicity. Three liposomal formulations were compared for delivery of ACP to a multidrug resistant tumor. METHODS: Three different liposomes ( DMPC, DPPC and DSPC as the main lipid components) were loaded with ACP by the thin-film hydration method. In vitro drug release was assessed over 72 h at 37°C in PBS. The pharmacokinetics of free CDDP and the three ACP liposomes was determined using ICP-AES and their efficacy against EMT6-AR1 multidrug resistant murine breast tumor was compared. RESULTS: The DSPC formulation, composed of a C18 acyl chain lipid, exhibited the slowest drug release (~2%) after 72 h at 37°C, compared to the other two formulations with decreased carbon chain lengths (C16 and C14; 7 and 25% release respectively). The pharmacokinetic profile was improved with all liposomal formulations relative to free CDDP, with clearance reduced by 500-fold for DSPC, 200-fold for DPPC and 130-fold for DMPC. The DSPC formulation displayed the highest drug accumulation in the tumor with 2-fold, 3-fold and 100-fold increases compared to DPPC, DMPC and free CDDP respectively. The DSPC formulation significantly inhibited the EMT6-AR1 tumor growth by ~90%, while the other formulations displayed no statistically significant improved activity compared to saline. CONCLUSION: These results suggest that the DSPC liposomal formulation is a promising formulation for MDR tumor therapy over DMPC and DPPC formulations and free drug.
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Authors | Yucheng Zhao, Jonathan P May, I-Wen Chen, Elijus Undzys, Shyh-Dar Li |
Journal | Pharmaceutical research
(Pharm Res)
Vol. 32
Issue 10
Pg. 3261-8
(Oct 2015)
ISSN: 1573-904X [Electronic] United States |
PMID | 25964047
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Drug Carriers
- Liposomes
- Phosphatidylcholines
- Cisplatin
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Topics |
- Animals
- Cell Proliferation
(drug effects)
- Chemistry, Pharmaceutical
(methods)
- Cisplatin
(chemistry, pharmacology)
- Drug Carriers
(chemistry)
- Drug Resistance, Neoplasm
(drug effects)
- Female
- Liposomes
(chemistry)
- Mice
- Mice, Inbred BALB C
- Neoplasms
(drug therapy)
- Phosphatidylcholines
(chemistry)
- Tissue Distribution
(drug effects)
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