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Molecules (Basel, Switzerland) Mar 2022A series of double-chain quaternary ammonium salt surfactants -['[3-(gluconamide)] propyl-'-alkyl]propyl-,-dimethyl--alkyl ammonium bromide (CDDGPB, where n represents a...
A series of double-chain quaternary ammonium salt surfactants -['[3-(gluconamide)] propyl-'-alkyl]propyl-,-dimethyl--alkyl ammonium bromide (CDDGPB, where n represents a hydrocarbon chain length of 8, 10, 12, 14 and 16) were successfully synthesized from D (+)-glucose δ-lactone, ,-dimethyldipropylenetriamine, and bromoalkane using a two-step method consisting of a proamine-ester reaction and postquaternization. Their surface activity, adsorption, and aggregation behavior in aqueous solution were investigated via measurements of dynamic/static surface tension, contact angle, dynamic light scattering, and transmission electron microscopy. An analysis of their application performance in terms of wettability, emulsifying properties, toxicity, and antibacterial properties was conducted. The results show that with increasing the carbon chain length of the CDDGPB surfactants, their critical micelle concentration (CMC) increased and the pC and efficiency in the interface adsorption of the target product gradually decreased. Moreover, the influence of the hydrophobic carbon chain length on the surface of polytetrafluoroethylene (PTFE) was even greater for the wetting effect, reducing the contact angle to 32° within the length range of C8-C14. The results of the contact angle change and the wettability experiments proved that CDDGPB exhibited the best wettability. The liquid paraffin and soybean oil emulsification ability of CDDGPB showed an upward trend followed by a downward trend with the growth of the carbon chain, with CDDGPB exhibiting the best emulsification performance. The D/D ratio was far lower than 1, which indicates mixed-kinetic adsorption. The surfactants formed spherical micelles and showed a unique aggregation behavior in aqueous solution, which showed an increase-decrease-increase trend with the change in concentration. A cell toxicity and acute oral toxicity experiment showed that the CDDGPB surfactants were less toxic than the commonly used surfactant dodecyldimethylbenzyl ammonium chloride (1227). In addition, at a concentration of 150 ppm, CDDGPB exhibited the same bacteriostatic effect as 1227 at a concentration of 100 ppm. The results demonstrate that sugar-based amide cationic surfactants are promising as environmentally friendly disinfection products.
Topics: Adsorption; Carbon; Micelles; Surface Tension; Surface-Active Agents; Water
PubMed: 35408549
DOI: 10.3390/molecules27072149 -
Molecules (Basel, Switzerland) Jul 2023Multistep one-pot polycondensation reactions synthesized amphiphilic diblock polyphosphoesters containing lactic acid units in the polymer backbone. At the first step...
Multistep one-pot polycondensation reactions synthesized amphiphilic diblock polyphosphoesters containing lactic acid units in the polymer backbone. At the first step was synthesized poly[poly(ethylene glycol) H-phosphonate--poly(ethylene glycol)lactate H-phosphonate] was converted through one pot oxidation into poly[alkylpoly(ethylene glycol) phosphate--alkylpoly(ethylene glycol)lactate phosphate]s. They were characterized by H, C {H},P NMR, and size exclusion chromatography (SEC). The effects of the polymer composition on micelle formation and stability, and micelle size were studied via dynamic light scattering (DLS). The hydrophilic/hydrophobic balance of these polymers can be controlled by changing the chain lengths of hydrophobic alcohols. Drug loading and encapsulation efficiency tests using Sudan III and doxorubicin revealed that hydrophobic substances can be incorporated inside the hydrophobic core of polymer micelles. The micelle size was 72-108 nm when encapsulating Sudan III and 89-116 nm when encapsulating doxorubicin. Loading capacity and encapsulation efficiency depend on the length of alkyl side chains. Changing the alkyl side chain from 8 to 16 carbon atoms increased micelle-encapsulated Sudan III and doxorubicin by 1.6- and 1.1-fold, respectively. The results obtained indicate that these diblock copolymers have the potential as drug carriers.
Topics: Micelles; Lactic Acid; Polyethylene Glycols; Polymers; Drug Carriers; Doxorubicin
PubMed: 37446904
DOI: 10.3390/molecules28135243 -
Biomaterials Jun 2021In atherosclerosis, resident vascular smooth muscle cells (VSMCs) in the blood vessels become highly plastic and undergo phenotypic switching from the quiescent,...
In atherosclerosis, resident vascular smooth muscle cells (VSMCs) in the blood vessels become highly plastic and undergo phenotypic switching from the quiescent, contractile phenotype to the migratory and proliferative, synthetic phenotype. Additionally, recent VSMC lineage-tracing mouse models of atherosclerosis have found that VSMCs transdifferentiate into macrophage-like and osteochondrogenic cells and make up to 70% of cells found in atherosclerotic plaques. Given VSMC phenotypic switching is regulated by microRNA-145 (miR-145), we hypothesized that nanoparticle-mediated delivery of miR-145 to VSMCs has the potential to mitigate atherosclerosis development by inhibiting plaque-propagating cell types derived from VSMCs. To test our hypothesis, we synthesized miR-145 micelles targeting the C-C chemokine receptor-2 (CCR2), which is highly expressed on synthetic VSMCs. When miR-145 micelles were incubated with human aortic VSMCs in vitro, >90% miR-145 micelles escaped the lysosomal pathway in 4 hours and released the miR cargo under cytosolic levels of glutathione, an endogenous reducing agent. As such, miR-145 micelles rescued atheroprotective contractile markers, myocardin, α-SMA, and calponin, in synthetic VSMCs in vitro. In early-stage atherosclerotic ApoE mice, one dose of miR-145 micelles prevented lesion growth by 49% and sustained an increased level of miR-145 expression after 2 weeks post-treatment. Additionally, miR-145 micelles inhibited 35% and 43% plaque growth compared to free miR-145 and PBS, respectively, in mid-stage atherosclerotic ApoE mice. Collectively, we present a novel therapeutic strategy and cell target for atherosclerosis, and present miR-145 micelles as a viable nanotherapeutic that can intervene atherosclerosis progression at both early and later stages of disease.
Topics: Animals; Atherosclerosis; Cell Proliferation; Cells, Cultured; Mice; Micelles; MicroRNAs; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Phenotype
PubMed: 33892346
DOI: 10.1016/j.biomaterials.2021.120810 -
Chemical Reviews Nov 2021Self-assembly is promising for construction of a wide variety of supramolecular assemblies, whose 1D/2D/3D structures are typically relevant to their functions. In-depth... (Review)
Review
Self-assembly is promising for construction of a wide variety of supramolecular assemblies, whose 1D/2D/3D structures are typically relevant to their functions. In-depth understanding of their structure-function relationships is essential for rational design and development of functional molecular assemblies. Microscopic imaging has been used as a powerful tool to elucidate structures of individual molecular assemblies with subnanometer to millimeter resolution, which is complementary to conventional spectroscopic techniques that provide the ensemble structural information. In this review, we highlight the representative examples of visualization of molecular assemblies by use of electron microscopy, atomic force microscopy, confocal microscopy, and super-resolution microscopy. This review comprehensively describes imaging of supramolecular nanofibers/gels, micelles/vesicles, coacervate droplets, polymer assemblies, and protein/DNA assemblies. Advanced imaging techniques that can address key challenges, like evaluation of dynamics of molecular assemblies, multicomponent self-assembly, and self-assembly/disassembly in complex cellular milieu, are also discussed. We believe this review would provide guidelines for deeper structural analyses of molecular assemblies to develop the next-generation materials.
Topics: Electrons; Micelles; Microscopy, Atomic Force; Microscopy, Confocal; Nanofibers
PubMed: 33942610
DOI: 10.1021/acs.chemrev.0c01334 -
European Journal of Pharmaceutical... Sep 2023Pazopanib (PZ) is a multikinase inhibitor, which is mainly used in the treatment of soft tissue sarcoma and advanced renal cancer. However, because of its water...
Pazopanib (PZ) is a multikinase inhibitor, which is mainly used in the treatment of soft tissue sarcoma and advanced renal cancer. However, because of its water insolubility, oral bioavailability is poor. At the same time, photo lability and high dose oral administration lead to severe hepatotoxicity, which is limited in clinical application. In this paper, the novel pazopanib-fumarate disodium glycyrrhizinate nanocrystalline micelles are successfully prepared by liquid-assisted ball milling. The prepared cocrystals and nanocrystalline micelle structures are systematically characterized by X-ray diffraction (XRD), differential scanning calorimetry (DSC) and Fourier Transform Infrared Spectrometer (FTIR) analysis. In vitro solubility and dissolution experiments show that the solubility and dissolution of nanocrystalline micelles are significantly improved under different simulated physiological conditions. The accelerated stabilization experiments show that the nanocrystalline micelles have good physical and chemical stability and showed excellent stability in water (Zeta potential was 62.39 mV). In addition, the in vivo bioavailability of nanocrystalline micelles is 3 times higher than that of PZ, and the therapeutic threshold (> 20 μg/mL) is up to 30 h. This new strategy provides a feasible solution to the undesirable properties of PZ.
Topics: Micelles; Fumarates; Solubility; Calorimetry, Differential Scanning; Glycyrrhetinic Acid; Water; X-Ray Diffraction; Biological Availability; Spectroscopy, Fourier Transform Infrared
PubMed: 37459902
DOI: 10.1016/j.ejps.2023.106530 -
Biochimica Et Biophysica Acta Jul 2016The structure and stability of membrane proteins can vary widely in different detergents and this variability has great practical consequences for working with membrane...
The structure and stability of membrane proteins can vary widely in different detergents and this variability has great practical consequences for working with membrane proteins. Nevertheless, the mechanisms that operate to alter the behavior of proteins in micelles are poorly understood and not predictable. Atomic simulations could provide considerable insight into these mechanisms. Building protein-micelle complexes for simulation is fraught with uncertainty, however, in part because it is often unknown how many detergent molecules are present in the complex. Here, we describe several convenient ways to employ Micelle Builder in CHARMM-GUI to rapidly construct protein-micelle complexes and performed simulations of the isolated voltage-sensor domain of voltage-dependent potassium-selective channel and an antimicrobial peptide papiliocin with varying numbers of detergents. We found that once the detergent number exceeds a threshold, protein-detergent interactions change very little and remain very consistent with experimental observations. Our results provide a platform for future studies of the interplays between protein structure and detergent properties at the atomic level. This article is part of a Special Issue entitled: Membrane Proteins edited by J.C. Gumbart and Sergei Noskov.
Topics: Biomimetic Materials; Detergents; Membrane Lipids; Membrane Proteins; Micelles; Models, Chemical; Molecular Dynamics Simulation; Protein Conformation; Software; Structure-Activity Relationship
PubMed: 26679426
DOI: 10.1016/j.bbamem.2015.12.012 -
Colloids and Surfaces. B, Biointerfaces Oct 2014Polymeric prodrug micelles for delivery of acyclovir (ACV) were synthesized. First, ACV was used directly to initiate ring-opening polymerization of ɛ-caprolactone to...
Polymeric prodrug micelles for delivery of acyclovir (ACV) were synthesized. First, ACV was used directly to initiate ring-opening polymerization of ɛ-caprolactone to form ACV-polycaprolactone (ACV-PCL). Through conjugation of hydrophobic ACV-PCL with hydrophilic methoxy poly(ethylene glycol) (MPEG) or chitosan, polymeric micelles for drug delivery were formed. (1)H NMR, FTIR, and gel permeation chromatography were employed to show successful conjugation of MPEG or chitosan to hydrophobic ACV-PCL. Through dynamic light scattering, zeta potential analysis, transmission electron microscopy, and critical micelle concentration (CMC), the synthesized ACV-tagged polymeric micelles were characterized. It was found that the average size of the polymeric micelles was under 200nm and the CMCs of ACV-PCL-MPEG and ACV-PCL-chitosan were 2.0mgL(-1) and 6.6mgL(-1), respectively. The drug release kinetics of ACV was investigated and cytotoxicity assay demonstrates that ACV-tagged polymeric micelles were non-toxic.
Topics: Acyclovir; Antiviral Agents; Chromatography, Gel; Drug Carriers; Micelles; Microscopy, Electron, Transmission; Polymers; Proton Magnetic Resonance Spectroscopy; Spectroscopy, Fourier Transform Infrared
PubMed: 25193154
DOI: 10.1016/j.colsurfb.2014.08.011 -
International Journal of Nanomedicine 2022Kidney-type glutaminase (KGA) has been an important anti-tumor drug target, and KGA allosteric inhibitors attracted much interest for their superior enzymatic...
INTRODUCTION
Kidney-type glutaminase (KGA) has been an important anti-tumor drug target, and KGA allosteric inhibitors attracted much interest for their superior enzymatic specificity with good drug safety profiles. For glutaminase allosteric inhibitors such as BPTES, CB-839 and Selen derivatives, the low solubility remains as the main factor that limits in vivo efficacy. The 1,3,4-Selenadiazole compound CPD 23 showed improved in vivo efficacy but worse solubility; however, the graft polymer polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol (PVCap-PVA-PEG), Soluplus (SOL) stood out as an excellent delivery carrier for CPD 23.
METHODS
The CPD 23@SOL micelles were prepared, optimized and evaluated through on the basis of solubility improvement and loading capacity. Characterizations of particle size and Zeta potential by dynamic light scattering, morphology by transmission electron microscopy and solid state by X-ray powder diffraction were closely conducted. The biological studies included the tumor cell growth inhibition, blood and liver microsomal stability, in vivo pharmacokinetics and tissue biodistribution.
RESULTS
At 1:20 ratio of CPD 23:SOL, CPD 23@SOL micelles were well-dispersed, spherical and stable, with size less than 200 nm with encapsulation efficiency of more than 90%. This SOL micellar system significantly increased the aqueous solubility of CPD 23 by 15,000 folds. Particularly, CPD 23@SOL micelles demonstrated higher stability in blood and liver microsomes, showing approximately 86% remaining at 2 h incubation and about 66% at 4 h, respectively. In addition, with or without micellar formulation, CPD 23 maintained essentially the same inhibitory activity in tumor cells. Interestingly, CPD 23@SOL micelles significantly improved the pharmacokinetic exposure, prolonged the in vivo circulation and dramatically changed tissue biodistributions of CPD 23.
CONCLUSION
The current work provided an encouraging and practical delivery system for novel Selenadiazoles and glutaminase allosteric inhibitors whose poor water-soluble characteristic has been a bottleneck for the field.
Topics: Drug Carriers; Glutaminase; Micelles; Polyethylene Glycols; Polymers; Solubility; Tissue Distribution
PubMed: 35058693
DOI: 10.2147/IJN.S346596 -
Methods in Enzymology 2022Biochemical analyses of membrane receptor kinases have been limited by challenges in obtaining sufficient homogeneous receptor samples for downstream structural and...
Biochemical analyses of membrane receptor kinases have been limited by challenges in obtaining sufficient homogeneous receptor samples for downstream structural and biophysical characterization. Here, we report a suite of methods for the efficient expression, purification, and visualization by cryo-electron microscopy (cryo-EM) of near full-length Human Epidermal Growth Factor Receptor 3 (HER3), a receptor tyrosine pseudokinase, in the unliganded state. Through transient mammalian cell expression, a two-step purification with detergent exchange into lauryl maltose neopentyl glycol (LMNG), and freezing devoid of background detergent micelle, we obtained ~6Å reconstructions of the ~60kDa fully-glycosylated unliganded extracellular domain of HER3 from just 30mL of suspension culture. The reconstructions reveal previously unappreciated extracellular domain dynamics and glycosylation sites.
Topics: Animals; Cryoelectron Microscopy; Detergents; Humans; Mammals; Micelles
PubMed: 35525556
DOI: 10.1016/bs.mie.2022.03.048 -
Advanced Science (Weinheim,... Apr 2022The cancer drug delivery process involves a series of biological barriers, which require the nanomedicine to exhibit different, even opposite properties for high...
The cancer drug delivery process involves a series of biological barriers, which require the nanomedicine to exhibit different, even opposite properties for high therapeutic efficacy. The prevailing design philosophy, i.e., integrating these properties within one nanomedicine via on-demand property transitions such as PEGylation/dePEGylation, complicates nanomedicines' composition and thus impedes clinical translation. Here, polyzwitterionic micelles of poly(tertiary amine-oxide)-block-poly(ε-caprolactone) (PTAO-PCL) amphiphiles that enable all the required functions are presented. The zwitterionic nature and unique cell membrane affinity confer the PTAO micelles long blood circulation, efficient tumor accumulation and penetration, and fast cellular internalization. The mitochondrial targeting capability allows drug delivery into the mitochondria to induce mitochondrial dysfunction and overcome tumor multidrug resistance. As a result, the PTAO/drug micelles exhibit potent anticancer efficacy. This simple yet multipotent carrier system holds great promise as a generic platform for potential clinical translation.
Topics: Amines; Antineoplastic Agents; Humans; Micelles; Neoplasms; Oxides
PubMed: 35187868
DOI: 10.1002/advs.202200173