The University of Southampton
University of Southampton Institutional Repository

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.

This record has no associated files available for download.

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

Catalogue record

Date deposited: 28 Mar 2022 16:38
Last modified: 21 Jun 2022 01:52

Export record

Altmetrics

Contributors

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

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×