Title

Thermosensitive Liposomes Encapsulating Nedaplatin and Picoplatin Demonstrate Enhanced Cytotoxicity against Breast Cancer Cells

Author's Department

Chemistry Department

All Authors

Sherif Ashraf Fahmy, Eduard Preis, Alice Abu Dayyih, Mohamed Alawak, Hassan Mohamed El-Said Azzazy, Udo Bakowsky, Tamer Shoeib

Document Type

Research Article

Publication Title

ACS Omega

Publication Date

Fall 11-7-2022

doi

https://doi.org/10.1021/acsomega.2c04525

Abstract

Thermosensitive liposomes (TSL) have been used for localized temperature-responsive release of chemotherapeutics into solid cancers, with a minimum of one invention currently in clinical trials (phase III). In this study, TSL was designed using a lipid blend comprising 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), cholesterol, and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[maleimide(polyethylene glycol)-2000] (DSPE-PEG-2000) (molar ratio of 88:9:2.8:0.2). Either nedaplatin (ND) or p-sulfonatocalix[4]arene-nedaplatin was encapsulated in the aqueous inner layer of TSL to form (ND-TSL) or p-SC4-ND-TSL, respectively. The hydrophobic platinum-based drug picoplatin (P) was loaded into the external lipid bilayer of the TSL to develop P-TSL. The three nanosystems were studied in terms of size, PDI, surface charge, and on-shelf stability. Moreover, the entrapment efficiency (EE%) and release % at 37 and 40 °C were evaluated. In a 30 min in vitro release study, the maximum release of ND, p-SC4-ND, and picoplatin at 40 °C reached 74, 79, and 75%, respectively, compared to approximately 10% at 37 °C. This demonstrated temperature-triggered drug release from the TSL in all three developed systems. The designed TSL exhibited significant in vitro anticancer activity at 40 °C when tested on human mammary gland/breast adenocarcinoma cells (MDA-MB-231). The cytotoxicity of ND-TSL, p-SC4-ND-TSL, and P-TSL at 40 °C was approximately twice those observed at 37 °C. This study suggests that TSL is a promising nanoplatform for the temperature-triggered release of platinum-based drugs into cancer cells.

First Page

42115

Last Page

42125

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