Cardinal Role of Intraliposome Doxorubicin-Sulfate Nanorod Crystal in Doxil Properties and Performance

ACS Omega
Xiaohui WeiYechezkel Barenholz

Abstract

The uniqueness of Doxil can be attributed, to a large extent, to its intraliposomal doxorubicin-sulfate nanorod crystal. We re-examine these nanocrystal features and their mechanism of the formation by studying pegylated liposomal doxorubicins (PLDs) of the same lipid composition, size distribution, and extraliposome medium that were prepared at different ammonium sulfate (AS) concentrations. This study includes a comparison of the thermotropic behavior, morphology, and in vitro ammonia-induced doxorubicin release (relevant to Doxil's in vivo performance) of these PLDs. In this study, we confirm that a transmembrane ammonium gradient is critical for doxorubicin remote loading, and we demonstrate that the intraliposomal concentration of sulfate counteranions and ammonium ions determine to a large extent the physical state and stability of the PLDs' remote loaded doxorubicin. "Fully-developed" intraliposome doxorubicin-sulfate nanorod crystals (as defined by cryogenic transmission electron microscopy imaging) develop only when the ammonium sulfate (AS) concentration used for PLD preparation is ≥150 mM. Less than 10% of PLDs prepared with 100 mM AS show fully developed nanorod crystals. Intraliposomal AS concentration ≥200 mM is r...Continue Reading

References

Nov 9, 1992·FEBS Letters·D D LasicT J McIntosh
Dec 1, 1990·Journal of Pharmaceutical Sciences·S AmselemY Barenholz
Jun 1, 1986·Chemistry and Physics of Lipids·D W Deamer, J Bramhall
Nov 1, 1995·Biochimica Et Biophysica Acta·D D LasicY Barenholz
Oct 12, 1994·Biochimica Et Biophysica Acta·V P TorchilinC A Gentry
Jul 1, 1993·Medicinal Research Reviews·Y BarenholzA Gabizon
Sep 13, 2002·Biochimica Et Biophysica Acta·Sheela Ann AbrahamMarcel B Bally
May 13, 2003·Clinical Pharmacokinetics·Alberto GabizonYechezkel Barenholz
May 1, 2010·The Journal of Physical Chemistry. B·Zoltán VargaAttila Bóta
Apr 10, 2012·Journal of Controlled Release : Official Journal of the Controlled Release Society·Yechezkel Barenholz
Jun 28, 2015·Nanomedicine : Nanotechnology, Biology, and Medicine·Lisa Silverman, Yechezkel Barenholz
Aug 28, 2015·Journal of Controlled Release : Official Journal of the Controlled Release Society·Kyle D FugitBradley D Anderson
Apr 24, 2016·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Xiaohui WeiYechezkel Barenholz

❮ Previous
Next ❯

Citations

Feb 6, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yaelle BavliKeren Turjeman
Jan 11, 2020·Frontiers in Bioengineering and Biotechnology·Oliver S Thomas, Wilfried Weber
Oct 16, 2019·Frontiers in Pharmacology·Ernest MolesXavier Fernàndez-Busquets
Jan 8, 2021·Chemistry and Physics of Lipids·Mehak RastogiSunil Kumar Dubey
Jan 19, 2021·Biochimica Et Biophysica Acta. General Subjects·Yaelle SchiltUri Raviv
Jan 9, 2021·Nature Chemical Biology·Ryan M WilliamsDaniel A Heller
May 23, 2020·Journal of Controlled Release : Official Journal of the Controlled Release Society·Clément GoubaultFabienne Gauffre
Jun 27, 2021·Advanced Drug Delivery Reviews·Marc-Phillip MastMatthias G Wacker
Nov 30, 2018·Molecular Pharmaceutics·Tang LiBen J Boyd
May 29, 2019·Molecular Pharmaceutics·Hassan TamamYoon Yeo

❮ Previous
Next ❯

Methods Mentioned

BETA
transmission
X-ray
differential scanning calorimetry
dynamic light scattering
light-scattering

Software Mentioned

Microcal LLC DSC workstation
MATLAB
Digital Micrograph

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V
Xiaohui WeiYechezkel Barenholz
The Journal of the Association of Nurses in AIDS Care : JANAC
D J Porche
© 2022 Meta ULC. All rights reserved