Low-Density Lipoproteins and Human Serum Albumin as Carriers of Squalenoylated Drugs: Insights from Molecular Simulations.

Mol Pharm

Institut Galien Paris-Sud, UMR 8612, CNRS, Univ Paris-Sud, Université Paris-Saclay, Faculté de Pharmacie , 5 rue Jean-Baptiste Clément, F-92296 Châtenay-Malabry Cedex, France.

Published: February 2018

We have studied the interaction of three clinically promising squalenoylated drugs (gemcitabine-squalene, adenine-squalene, and doxorubicin-squalene) with low-density lipoproteins (LDL) by means of atomistic molecular dynamics simulations. It is shown that all studied squalenoylated drugs accumulate inside the LDL particles. This effect is promoted by the squalene moiety, which acts as an anchor and drives the hydrophilic drugs into the hydrophobic core of the LDL lipid droplet. Our data suggest that LDL particles could be a universal carriers of squalenoylated drugs in the bloodstream. Interaction of gemcitabine-squalene with human serum albumin (HSA) was also studied by ensemble of docking simulations. It is shown that HSA could also act as a passive carrier of this bioconjugate. It should be noted that the binding of squalene moiety to HSA was unspecific and did not occur in the binding pockets devoted to fatty acids.

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.molpharmaceut.7b00952DOI Listing

Publication Analysis

Top Keywords

squalenoylated drugs
16
low-density lipoproteins
8
human serum
8
serum albumin
8
carriers squalenoylated
8
simulations studied
8
ldl particles
8
squalene moiety
8
drugs
5
lipoproteins human
4

Similar Publications

We explored the potential of overcoming the dense interstitial barrier in pancreatic cancer treatment by enhancing the uptake of hydrophilic chemotherapeutic drugs. In this study, we synthesized the squalenoyl-chidamide prodrug (SQ-CHI), linking lipophilic squalene (SQ) with the hydrophilic antitumor drug chidamide (CHI) through a trypsin-responsive bond. Self-assembled nanoparticles with sigma receptor-bound aminoethyl anisamide (AEAA) modification, forming AEAA-PEG-SQ-CHI NPs (A-C NPs, size 116.

View Article and Find Full Text PDF

Intracellular distribution of doxorubicin (DOX) and its squalenoylated (SQ-DOX) nanoparticles (NPs) form in murine lung carcinoma M109 and human breast carcinoma MDA-MB-231 cells was investigated by Raman microspectroscopy. Pharmacological data showed that DOX induced higher cytotoxic effect than SQ-DOX NPs. Raman data were obtained using single-point measurements and imaging on the whole cell areas.

View Article and Find Full Text PDF

(Poly-cyanoacrylate) nanomedicines for cancer and beyond: Lessons learned.

J Control Release

June 2021

Institut Galien Paris-Sud, UMR 8612, CNRS, Univ Paris-Sud, Université Paris-Saclay, Faculté de Pharmacie, 5 rue Jean-Baptiste Clément, F-92296 Châtenay-Malabry, Cedex, France.. Electronic address:

This « Magnum Opus » emphasizes that serendipity is a corner stone in research. The paths of discovery and innovation often result from the interdisciplinarity of scientific areas that are a priori disconnected from each other. In the 1970s, fundamental discoveries in cell biology led to unexpected advances in galenic pharmacy with the emergence of nanotechnologies for the intracellular delivery of non diffusing molecules.

View Article and Find Full Text PDF

Charcot-Marie-Tooth disease type 1 A (CMT1A) lacks an effective treatment. We provide a therapy for CMT1A, based on siRNA conjugated to squalene nanoparticles (siRNA PMP22-SQ NPs). Their administration resulted in normalization of Pmp22 protein levels, restored locomotor activity and electrophysiological parameters in two transgenic CMT1A mouse models with different severity of the disease.

View Article and Find Full Text PDF

Self-Assembled Amphiphilic Starch Based Drug Delivery Platform: Synthesis, Preparation, and Interactions with Biological Barriers.

Biomacromolecules

February 2021

Kusudama Therapeutics, Parque Científico y Tecnológico de Gipuzkoa, Donostia-San, Sebastián 20014, Spain.

Core-shell structured nanoparticles (NPs) render the simultaneous coloading capacity of both hydrophobic and hydrophilic drugs and may eventually enhance therapeutic efficacy. In this study, we employed a facile squalenoylation technology to synthesize a new amphiphilic starch derivative from partially oxidized starch, which self-assembled into core-shell starch NPs (StNPs) only at a squalenyl degree of substitution (DoS) of ∼1%. The StNPs characteristics could be tuned as the functions of the polymer molecular weight, DoS, and NPs concentration.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!