Micellar nanocarriers assembled from doxorubicin-conjugated amphiphilic macromolecules (DOX-AM)

Macromolecular Bioscience
Leilani S del RosarioKathryn E Uhrich

Abstract

Amphiphilic macromolecules (AMs) have unique branched hydrophobic domains attached to linear PEG chains. AMs self-assemble in aqueous solution to form micelles that are hydrolytically stable in physiological conditions (37 degrees C, pH 7.4) over 4 weeks. Evidence of AM biodegradability was demonstrated by complete AM degradation after 6 d in the presence of lipase. Doxorubicin (DOX) was chemically conjugated to AMs via a hydrazone linker to form DOX-AM conjugates that self-assembled into micelles in aqueous solution. The conjugates were compared with DOX-loaded AM micelles (i.e., physically loaded DOX) on DOX content, micellar sizes and in vitro cytotoxicity. Physically encapsulated DOX loading was higher (12 wt.-%) than chemically bound DOX (6 wt.-%), and micellar sizes of DOX-loaded AMs (approximately 16 nm) were smaller than DOX-AMs (approximately 30 nm). In vitro DOX release from DOX-AM conjugates was faster at pH 5.0 (100%) compared to pH 7.4 (78%) after 48 h, 37 degrees C. Compared to free DOX and physically encapsulated DOX, chemically bound DOX had significantly higher cytotoxicity at 10(-7) M DOX dose against human hepatocellular carcinoma cells after 72 h. Overall, DOX-AM micelles showed promising characteristics as ...Continue Reading

References

Dec 1, 1992·Canadian Journal of Microbiology·A Fonseca
Feb 1, 1995·Pharmaceutical Research·G S KwonK Kataoka
Aug 1, 1998·Journal of Controlled Release : Official Journal of the Controlled Release Society·M YokoyamaT Okano
Sep 19, 1998·Journal of Controlled Release : Official Journal of the Controlled Release Society·V OmelyanenkoJ Kopecek
Sep 2, 1999·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·M Jones, J Leroux
Jan 21, 2000·Journal of Controlled Release : Official Journal of the Controlled Release Society·K KataokaG S Kwon
Mar 4, 2000·Journal of Controlled Release : Official Journal of the Controlled Release Society·H MaedaK Hori
Sep 7, 2000·Journal of Controlled Release : Official Journal of the Controlled Release Society·H S YooT G Park
Feb 13, 2001·Journal of Controlled Release : Official Journal of the Controlled Release Society·H S Yoo, T G Park
May 5, 2001·Journal of Controlled Release : Official Journal of the Controlled Release Society·T EtrychK Ulbrich
Jan 5, 2002·Journal of Controlled Release : Official Journal of the Controlled Release Society·Fukashi KohoriTeruo Okano
Feb 22, 2002·Cancer Chemotherapy and Pharmacology·Terence Kin-Wah LeeIrene Oi-Lin Ng
Apr 12, 2002·Journal of Controlled Release : Official Journal of the Controlled Release Society·Ondrej HovorkaB Ríhová
May 16, 2002·Bioconjugate Chemistry·Henrik R IhreJean M J Fréchet
Jul 11, 2002·Journal of Controlled Release : Official Journal of the Controlled Release Society·Hyuk Sang YooTae Gwan Park
Feb 5, 2003·Advanced Drug Delivery Reviews·Richard B GreenwaldCharles D Conover
Mar 6, 2003·Journal of Controlled Release : Official Journal of the Controlled Release Society·K UlbrichB Ríhová
Mar 6, 2003·Journal of Controlled Release : Official Journal of the Controlled Release Society·Keith D JensenJindrich Kopecek
Mar 12, 2003·Advanced Drug Delivery Reviews·R J Christie, D W Grainger
May 17, 2003·Nature Reviews. Drug Discovery·Ruth Duncan
Dec 23, 2003·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·A DavidJ Kopecek
May 26, 2004·International Journal of Pharmaceutics·K UlbrichB Rihova
May 26, 2004·International Journal of Pharmaceutics·K HosteE Schacht
Sep 24, 2004·Journal of Controlled Release : Official Journal of the Controlled Release Society·M KovárB Ríhová
Jan 18, 2005·Journal of Controlled Release : Official Journal of the Controlled Release Society·Zhong-Gao GaoNatalya Rapoport
Feb 16, 2005·Journal of Controlled Release : Official Journal of the Controlled Release Society·Martin HrubýKarel Ulbrich
Mar 15, 2005·Journal of Controlled Release : Official Journal of the Controlled Release Society·Eun Seong LeeYou Han Bae
Mar 17, 2005·Bioconjugate Chemistry·Elizabeth R Gillies, Jean M J Fréchet
Jan 13, 2006·Journal of Colloid and Interface Science·Li Tao, Kathryn E Uhrich
Aug 8, 2006·Journal of Controlled Release : Official Journal of the Controlled Release Society·Refika I PakunluTamara Minko
Nov 1, 2006·Proceedings of the National Academy of Sciences of the United States of America·Cameron C LeeFrancis C Szoka
Nov 17, 2006·Pharmaceutical Research·V P Torchilin
Mar 1, 2007·Biomacromolecules·Yong HuChangzheng Yang
Sep 18, 2007·Journal of Controlled Release : Official Journal of the Controlled Release Society·A MaluginJ Kopecek
Sep 21, 2007·Journal of Pharmaceutical Sciences·Myrra G CarstensWim E Hennink
Nov 13, 2007·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Fu-Qiang HuHong Yuan
Dec 22, 2007·International Journal of Pharmaceutics·Yi-Qing YeHe-Yong Yu
Feb 29, 2008·Journal of Controlled Release : Official Journal of the Controlled Release Society·P ChytilK Ulbrich

❮ Previous
Next ❯

Citations

Jun 6, 2012·Journal of Controlled Release : Official Journal of the Controlled Release Society·Qihang SunYouqing Shen
Oct 2, 2015·Journal of Controlled Release : Official Journal of the Controlled Release Society·Yingyue ZhangKathryn E Uhrich
Dec 14, 2015·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Mengni HeQianwang Chen
Jan 16, 2013·Chemical Communications : Chem Comm·Sandra Binauld, Martina H Stenzel
May 10, 2020·Current Drug Delivery·Panagiotis Theodosis-NobelosMaria Rikkou-Kalourkoti
Jun 15, 2012·Molecular Pharmaceutics·Katarzyna RudzkaJulián L Viota
Aug 21, 2014·Accounts of Chemical Research·Li GuKathryn Uhrich

❮ Previous
Next ❯

Related Concepts

Related Feeds

Carcinoma, Hepatocellular

Hepatocellular Carcinoma is a malignant cancer in liver epithelial cells. Discover the latest research on Hepatocellular Carcinoma here.