Preserving the Integrity of Liposomes Prepared by Ethanol Injection upon Freeze-Drying: Insights from Combined Molecular Dynamics Simulations and Experimental Data

Pharmaceutics
Silvia FranzèFrancesco Cilurzo

Abstract

The freeze-drying of complex formulations, such as liposomes, is challenging, particularly if dispersions contain residual organic solvents. This work aimed to investigate the effects of possible protectants, namely sucrose, trehalose and/or poly(vinyl pyrrolidone) (PVP), on the main features of the dried product using a 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC)-based liposomal dispersion prepared by ethanol injection and containing ethanol up to 6%, as a model. The interactions among vesicles and protectants were preliminary screened by Molecular Dynamics (MD) simulations, which have been proved useful in rationalizing the selection of protectant(s). The freeze-drying protocol was based on calorimetric results. Overall data suggested a stronger cryo-protectant effect of trehalose, compared with sucrose, due to stronger interactions with the DPPC bilayer and the formation of highly ordered clusters around the lipids. The effect further improved in the presence of PVP. Differently from the other tested protectants, the selected trehalose/PVP combination allows to preserve liposome size, even in the presence of 6% ethanol, as demonstrated by Nanoparticle Tracking Analysis (NTA). Nevertheless, it should be also underlined...Continue Reading

References

Feb 19, 2002·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Dirk L Teagarden, David S Baker
Nov 5, 2002·Journal of Molecular Graphics & Modelling·Alessandro PedrettiGiulio Vistoli
Feb 27, 2003·Journal of Liposome Research·Andreas WagnerHermann Katinger
Mar 23, 2004·Pharmaceutical Research·Xiaolin Tang, Michael J Pikal
Jun 11, 2005·The Journal of Chemical Physics·Sau Lawrence LeeJeffrey R Errington
Oct 14, 2005·Journal of Computational Chemistry·James C PhillipsKlaus Schulten
Feb 14, 2006·Biochimica Et Biophysica Acta·Satoshi OhtakeJuan J de Pablo
Nov 23, 2006·Advanced Drug Delivery Reviews·Wassim AbdelwahedHatem Fessi
May 18, 2011·Circulation·Diane E HandyJoseph Loscalzo
Apr 30, 1998·The Journal of Physical Chemistry. B·A D MacKerellM Karplus
Jan 2, 2016·International Journal of Pharmaceutics·Félix SauvageJuliette Vergnaud-Gauduchon
Mar 28, 2017·Journal of Pharmaceutical Sciences·Sajal Manubhai PatelShailaja Rambhatla Gupta
Apr 2, 2017·International Journal of Pharmaceutics·Irene OddoneRoberto Pisano
Apr 15, 2017·Molecular Pharmaceutics·Silvia FranzéFrancesco Cilurzo
Jun 20, 2017·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Paolo RoccoAlessandro Pedretti
Aug 23, 2017·The Journal of Physical Chemistry. B·Andrea Arsiccio, Roberto Pisano
Mar 13, 2018·Physical Chemistry Chemical Physics : PCCP·Andrea Arsiccio, Roberto Pisano
Apr 13, 2018·Journal of Pharmaceutical Sciences·Claudia Kunz, Henning Gieseler
Apr 28, 2018·Pharmaceutical Research·Andrea Arsiccio, Roberto Pisano
Aug 30, 2018·Pharmaceutics·Silvia FranzéFrancesco Cilurzo

❮ Previous
Next ❯

Citations

May 31, 2021·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Eduard Trenkenschuh, Wolfgang Friess

❮ Previous
Next ❯

Methods Mentioned

BETA
dynamic light scattering
Differential

Software Mentioned

MOPAC
VEGA ZZ
CHARMM
Windows
CUDA
Star e System
NAMD

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.