Transfer of MPEG(1900)-DSPE from micellar phase to pre-formed liposomes imparts long in vivo circulation half-life to an otherwise rapidly cleared lipid composition. MPEG(1900)-DSPE transfers efficiently and quickly in a time and temperature dependent manner. There is negligible content leakage and a strong correlation between assayed mol% MPEG(1900)-DSPE, liposome diameter increase, and pharmacokinetic parameters such as distribution phase half-life. Since a biological attribute (liposome clearance rate) can be modified by the insertion process, it suggests a simple and economical way to impart site-specific targeting to a variety of liposome delivery systems. This method is also a convenient way to measure the 'brush' thickness of such conjugates directly.
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http://dx.doi.org/10.1016/0014-5793(96)00452-8 | DOI Listing |
Mol Ther Nucleic Acids
September 2024
Department of Chemistry, Carleton University, Ottawa, ON K1S 5B6, Canada.
A neuropathological hallmark of Parkinson's disease (PD) is the aggregation and spreading of misfolded α-synuclein (αSyn) protein. In this study, a selection method was developed to identify aptamers that showed affinity for monomeric αSyn and inhibition of αSyn aggregation. Aptamer exhibited strong inhibition of αSyn aggregation by transmission electron microscopy and Thioflavin T fluorescence.
View Article and Find Full Text PDFCell Death Discov
July 2024
CNRS, Université de Bordeaux, UMR 5095, IBGC, Bordeaux, France.
Membrane insertion of the pro-apoptotic protein Bax was investigated by setting up cell-free synthesis of full-length Bax in the presence of pre-formed nanodiscs. While Bax was spontaneously poorly inserted in nanodiscs, co-synthesis with the mitochondrial receptor Tom22 stimulated Bax membrane insertion. The initial interaction of Bax with the lipid bilayer exposed the hydrophobic GALLL motif in Hα1 leading to Bax precipitation through hydrophobic interactions.
View Article and Find Full Text PDFAdv Healthc Mater
August 2024
John A. Paulson School of Engineering and Applied Sciences, Harvard University, 150 Western Ave, Allston, MA, 02134, USA.
Molecules
March 2024
Laboratory of Pharmaceutical Technology, Department of Pharmacy, School of Health Sciences, University of Patras, 26510 Rio Patras, Greece.
With the aim to develop novel scaffolds for the sustained release of drugs, we initially developed an easy approach for the synthesis of α,ω-homobifunctional mercaptoacyl poly(alkyl oxide)s. This was based on the esterification of the terminal hydroxyl groups of poly(alkyl oxide)s with suitably -4-methoxytrityl (Mmt)-protected mercapto acids, followed by the removal of the acid labile -Mmt group. This method allowed for the efficient synthesis of the title compounds in high yield and purity, which were further used in the development of a thioether cross-linked liposome scaffold, by thia-Michael reaction of the terminal thiol groups with pre-formed nano-sized liposomes bearing maleimide groups on their surface.
View Article and Find Full Text PDFAdv Drug Deliv Rev
May 2024
Department of Pharmacy, University of Naples Federico II, Via D. Montesano, 49 80131 Naples, Italy. Electronic address:
Among non-viral vectors, lipid nanovectors are considered the gold standard for the delivery of RNA therapeutics. The success of lipid nanoparticles for RNA delivery, with three products approved for human use, has stimulated further investigation into RNA therapeutics for different pathologies. This requires decoding the pathological intracellular processes and tailoring the delivery system to the target tissue and cells.
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