Back to Search Start Over

Estrone-targeted liposomes for mitoxantrone delivery via estrogen receptor: In vivo targeting efficacy, antitumor activity, acute toxicity and pharmacokinetics.

Authors :
Xu G
Tang H
Chen J
Zhu M
Xie Y
Li Y
Hao Q
Sun Y
Cong D
Meng Q
Ren Z
Li Q
Bao H
Lv Z
Li Y
Pei J
Source :
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences [Eur J Pharm Sci] 2021 Jun 01; Vol. 161, pp. 105780. Date of Electronic Publication: 2021 Mar 02.
Publication Year :
2021

Abstract

Estrogen receptor (ER) is a potential target receptor for ER-positive cancer therapy including breast cancers, gastric cancers, and human acute myeloblastic leukaemia. In order to reduce the side-effects of mitoxantrone (MTO), estrone-targeted liposomes for MTO delivery via ER were designed for selectively targeting cancer cells. In previous studies, MTO-loaded estrogen receptor targeted and sterically stabilized liposome (ES-SSL-MTO; ES: estrone, is known to bind the ER) had been synthesized and showed a very high antiproliferative effect with IC <subscript>50</subscript> value of 0.7 ng/mL. Based on these, further studies including in vivo targeting efficacy and antitumor activity, acute toxicity and pharmacokinetics of MTO liposomes were carried out. The results showed SSL (sterically stabilized liposome, PEGylated liposome, PEG: Polyethylene Glycol) could reduce drug metabolism, improve the stability of liposomes, prolong in vivo circulation time of drugs, reduce the toxicity of MTO. But SSL could not be enriched in tumor tissues. However, estrone (ES)-targeted liposomes could be delivered to tumor sites. ES-SSL could effectively enter into ER-expressing tumor cellsand be accumulated, prolong the circulation time in vivo, reduce side effects of drug. ES-SSL-MTO could provide higher bioavailability than MTO, enhance the anti-tumor effect and the safety of MTO, reduce the toxicity and side effects of MTO and improve the therapeutic effect of MTO. These facts proved ES-SSL is a useful tumor-targeting drug delivery system for MTO.<br /> (Copyright © 2021. Published by Elsevier B.V.)

Details

Language :
English
ISSN :
1879-0720
Volume :
161
Database :
MEDLINE
Journal :
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
Publication Type :
Academic Journal
Accession number :
33667664
Full Text :
https://doi.org/10.1016/j.ejps.2021.105780