Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

Liposomal delivery of hydrophobic RAMBAs provides good bioavailability and significant enhancement of retinoic acid signalling in neuroblastoma tumour cells

Bilip, Maja, Shah, Shreya, Mathiyalakan, Mayuran, Tagalakis, Aristides, Hart, Stephen L., Maeshima, Ruhina, Eaton, Simon, Orford, Michael, Irving, Elsa, Di Florio, Alessia, Simons, Claire and Stoker, Andrew W 2020. Liposomal delivery of hydrophobic RAMBAs provides good bioavailability and significant enhancement of retinoic acid signalling in neuroblastoma tumour cells. Journal of Drug Targeting 28 (6) , pp. 643-654. 10.1080/1061186X.2019.1710157

[img]
Preview
PDF - Accepted Post-Print Version
Download (1MB) | Preview

Abstract

Retinoid treatment is employed during residual disease treatment in neuroblastoma, where the aim is to induce neural differentiation or death in tumour cells. However, although therapeutically effective, retinoids have only modest benefits and suffer from poor pharmacokinetic properties. In vivo, retinoids induce CYP26 enzyme production in the liver, enhancing their own rapid metabolic clearance, while retinoid resistance in tumour cells themselves is considered to be due in part to increased CYP26 production. Retinoic acid metabolism blocking agents (RAMBAs), which inhibit CYP26 enzymes, can improve retinoic acid pharmacokinetics in pre-clinical neuroblastoma models. Here we demonstrate that in cultured neuroblastoma tumour cells, RAMBAs enhance retinoic acid action as seen by morphological differentiation, AKT signalling and suppression of MYCN protein. Although active as retinoid enhancers, these RAMBAs are highly hydrophobic and their effective delivery in humans will be very challenging. Here we demonstrate that such RAMBAs can be loaded efficiently into cationic liposomal particles, where the RAMBAs achieve good bioavailability and activity in cultured tumour cells. This demonstrates the efficacy of RAMBAs in enhancing retinoid signaling in neuroblastoma cells and shows for the first time that liposomal delivery of hydrophobic RAMBAs is a viable approach, providing novel opportunities for their delivery and application in humans.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Pharmacy
Publisher: Informa Healthcare
ISSN: 1061-186X
Date of First Compliant Deposit: 6 January 2020
Date of Acceptance: 26 December 2019
Last Modified: 20 Jan 2021 01:59
URI: http://orca.cardiff.ac.uk/id/eprint/128235

Citation Data

Cited 1 time in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item

Downloads

Downloads per month over past year

View more statistics