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A Study of Liposomal Formulations to Improve the Delivery of Aquated Cisplatin to a Multidrug Resistant Tumor

A Study of Liposomal Formulations to Improve the Delivery of Aquated Cisplatin to a Multidrug Resistant Tumor
A Study of Liposomal Formulations to Improve the Delivery of Aquated Cisplatin to a Multidrug Resistant Tumor

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.

aquated cisplatin, cisplatin, long circulating liposome, multidrug resistant tumor
0724-8741
3261-3268
Zhao, Yucheng
3e90ac1b-e89c-46d0-891b-79a2e97e2408
May, Jonathan P.
b54a262b-9f32-4435-8866-3b9c495294f3
Chen, I. Wen
126099ac-25f3-467e-8ab9-4a09cabef339
Undzys, Elijus
226e7879-8bef-4715-9e72-d405e59d6dcb
Li, Shyh Dar
9a960896-36e7-4eb8-bd39-55580c60e36d
Zhao, Yucheng
3e90ac1b-e89c-46d0-891b-79a2e97e2408
May, Jonathan P.
b54a262b-9f32-4435-8866-3b9c495294f3
Chen, I. Wen
126099ac-25f3-467e-8ab9-4a09cabef339
Undzys, Elijus
226e7879-8bef-4715-9e72-d405e59d6dcb
Li, Shyh Dar
9a960896-36e7-4eb8-bd39-55580c60e36d

Zhao, Yucheng, May, Jonathan P., Chen, I. Wen, Undzys, Elijus and Li, Shyh Dar (2015) A Study of Liposomal Formulations to Improve the Delivery of Aquated Cisplatin to a Multidrug Resistant Tumor. Pharmaceutical Research, 32 (10), 3261-3268. (doi:10.1007/s11095-015-1702-6).

Record type: Article

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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More information

Accepted/In Press date: 22 April 2015
Published date: 26 October 2015
Keywords: aquated cisplatin, cisplatin, long circulating liposome, multidrug resistant tumor

Identifiers

Local EPrints ID: 455575
URI: http://eprints.soton.ac.uk/id/eprint/455575
ISSN: 0724-8741
PURE UUID: b77449af-f67c-4f01-9d51-57ac6ed426b9
ORCID for Jonathan P. May: ORCID iD orcid.org/0000-0003-1651-130X

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Date deposited: 28 Mar 2022 16:38
Last modified: 18 Mar 2024 03:49

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Contributors

Author: Yucheng Zhao
Author: Jonathan P. May ORCID iD
Author: I. Wen Chen
Author: Elijus Undzys
Author: Shyh Dar Li

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