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Molecules (Basel, Switzerland) Sep 2022Using a novel strategy, amphiphilic polyphosphoesters based on poly(oxyethylene H-phosphonate)s (POEHP) with different poly(ethylene glycol) segment lengths and...
Using a novel strategy, amphiphilic polyphosphoesters based on poly(oxyethylene H-phosphonate)s (POEHP) with different poly(ethylene glycol) segment lengths and aliphatic alcohols with various alkyl chain lengths were synthesized using polycondensation reactions. They were characterized by H NMR, C {H} NMR P NMR, IR, and size exclusion chromatography (SEC). The effects of the polymer structure on micelle formation and stability, micelle size, and critical micelle temperature were studied via dynamic light scattering (DLS). The hydrophilic/hydrophobic balance of these polymers can be controlled by changing the chain lengths of hydrophilic PEG and hydrophobic alcohols. A solubilizing test, using Sudan III, revealed that hydrophobic substances can be incorporated inside the hydrophobic core of polymer associates. Loading capacity depends on the length of alkyl side chains. The results obtained indicate that these structurally flexible polymers have the potential as drug carriers.
Topics: Drug Carriers; Micelles; Organophosphonates; Polyethylene Glycols; Polymers
PubMed: 36144742
DOI: 10.3390/molecules27186006 -
Biochimica Et Biophysica Acta May 2016Isothermal titration calorimetry (ITC) is a general technique that allows for precise and highly sensitive measurements. These measurements may provide a complete and... (Review)
Review
BACKGROUND
Isothermal titration calorimetry (ITC) is a general technique that allows for precise and highly sensitive measurements. These measurements may provide a complete and accurate thermodynamic description of association processes in complex systems such as colloidal mixtures.
SCOPE OF THE REVIEW
This review will address uses of ITC for studies of surfactant aggregation to form micelles, with emphasis on the thermodynamic studies of homologous surfactant series. We will also review studies on surfactant association with polymers of different molecular characteristics and with colloidal particles.
GENERAL SIGNIFICANCE
ITC studies on the association of different homologous series of surfactants provide quantitative information on independent contribution from their apolar hydrocarbon chains and polar headgroups to the different thermodynamic functions associated with micellization (Gibbs energy, enthalpy and entropy). Studies on surfactant association to polymers by ITC provide a comprehensive description of the association process, including examples in which particular features revealed by ITC were elucidated by using ancillary techniques such as light or X-ray scattering measurements. Examples of uses of ITC to follow surfactant association to biomolecules such as proteins or DNA, or nanoparticles are also highlighted. Finally, recent theoretical models that were proposed to analyze ITC data in terms of binding/association processes are discussed.
MAJOR CONCLUSIONS
This review stresses the importance of using direct calorimetric measurements to obtain and report accurate thermodynamic data, even in complex systems. These data, whenever possible, should be confirmed and associated with other ancillary techniques that allow elucidation of the nature of the transformations detected by calorimetric results, providing a complete description of the process under scrutiny.
Topics: Calorimetry; Colloids; DNA; Hydrophobic and Hydrophilic Interactions; Micelles; Nanoparticles; Proteins; Static Electricity; Surface-Active Agents; Temperature; Thermodynamics
PubMed: 26459003
DOI: 10.1016/j.bbagen.2015.10.003 -
Journal of Pharmaceutical Sciences Mar 2023Multi-injection pharmaceutical products such as insulin must be formulated to prevent aggregation and microbial contamination. Small-molecule preservatives and nonionic...
Multi-injection pharmaceutical products such as insulin must be formulated to prevent aggregation and microbial contamination. Small-molecule preservatives and nonionic surfactants such as poloxamer 188 (P188) are thus often employed in protein drug formulations. However, mixtures of preservatives and surfactants can induce aggregation and even phase separation over time, despite the fact that all components are well dissolvable when used alone in aqueous solution. A systematic study is conducted here to understand the phase behavior and morphological causes of aggregation of P188 in the presence of the preservatives phenol and benzyl alcohol, primarily using small-angle x-ray scattering (SAXS). Based on SAXS results, P188 remains as unimers in solution when below a certain phenol concentration. Upon increasing the phenol concentration, a regime of micelle formation is observed due to the interaction between P188 and phenol. Further increasing the phenol concentration causes mixtures to become turbid and phase-separate over time. The effect of benzyl alcohol on the phase behavior is also investigated.
Topics: Poloxamer; Micelles; Scattering, Small Angle; X-Rays; X-Ray Diffraction; Surface-Active Agents; Water; Preservatives, Pharmaceutical; Phenols; Benzyl Alcohols; Solutions
PubMed: 36150467
DOI: 10.1016/j.xphs.2022.09.019 -
International Journal of Nanomedicine 2022We designed a novel isoliquiritigenin (ISL) loaded micelle prepared with DSPE-PEG as the drug carrier modified with the brain-targeting polypeptide angiopep-2 to improve...
Long-Circulation and Brain Targeted Isoliquiritigenin Micelle Nanoparticles: Formation, Characterization, Tissue Distribution, Pharmacokinetics and Effects for Ischemic Stroke.
PURPOSE
We designed a novel isoliquiritigenin (ISL) loaded micelle prepared with DSPE-PEG as the drug carrier modified with the brain-targeting polypeptide angiopep-2 to improve the poor water solubility and low bioavailability of ISL for the treatment of acute ischemic stroke.
METHODS
Thin film evaporation was used to synthesize the ISL micelles (ISL-M) modified with angiopep-2 as the brain targeted ligands. The morphology of the micelles was observed by the TEM. The particle size and zeta potential were measured via the nanometer particle size analyzer. The drug loading, encapsulation and in vitro release rates of micelles were detected by the HPLC. The UPLC-ESI-MS/MS methods were used to measure the ISL concentrations of ISL in plasma and main tissues after intravenous administration, and compared the pharmacokinetics and tissue distributions between ISL and ISL-M. In the MCAO mice model, the protective effects of ISL and ISL-M were confirmed via the behavioral and molecular biology experiments.
RESULTS
The results showed that the drug loading of ISL-M was 7.63 ± 2.62%, the encapsulation efficiency was 68.17 ± 6.23%, the particle size was 40.87 ± 4.82 nm, and the zeta potential was -34.23 ± 3.35 mV. The in vitro release experiments showed that ISL-M had good sustained-release effect and pH sensitivity. Compared with ISL monomers, the ISL-M could significantly prolong the in vivo circulation time of ISL and enhance the accumulation in the brain tissues. The ISL-M could ameliorate the brain injury induced by the MCAO mice via inhibition of cellular autophagy and neuronal apoptosis. There were no the cellular structural damages and other adverse effects for ISL-M on the main tissues and organs.
CONCLUSION
The ISL-M could serve as a promising and ideal drug candidate for the clinical application of ISL in the treatment of acute ischemic stroke.
Topics: Animals; Brain; Chalcones; Ischemic Stroke; Mice; Micelles; Nanoparticles; Tandem Mass Spectrometry; Tissue Distribution
PubMed: 35999993
DOI: 10.2147/IJN.S368528 -
Annual Review of Food Science and... Feb 2017In lipid dispersions, the ability of reactants to move from one lipid particle to another is an important, yet often ignored, determinant of lipid oxidation and its... (Review)
Review
In lipid dispersions, the ability of reactants to move from one lipid particle to another is an important, yet often ignored, determinant of lipid oxidation and its inhibition by antioxidants. This review describes three putative interparticle transfer mechanisms for oxidants and antioxidants: (a) diffusion, (b) collision-exchange-separation, and (c) micelle-assisted transfer. Mechanism a involves the diffusion of molecules from one particle to another through the intervening aqueous phase. Mechanism b involves the transfer of molecules from one particle to another when the particles collide with each other. Mechanism c involves the solubilization of molecules in micelles within the aqueous phase and then their transfer between particles. During lipid oxidation, the accumulation of surface-active lipid hydroperoxides (LOOHs) beyond their critical micelle concentration may shift their mass transport from the collision-exchange-separation pathway (slow transfer) to the micelle-assisted mechanism (fast transfer), which may account for the transition from the initiation to the propagation phase. Similarly, the cut-off effect governing antioxidant activity in lipid dispersions may be due to the fact that above a certain hydrophobicity, the transfer mechanism for antioxidants changes from diffusion to collision-exchange-separation. This hypothesis provides a simple model to rationalize the design and formulation of antioxidants and dispersed lipids.
Topics: Antioxidants; Diffusion; Lipid Peroxides; Lipids; Micelles; Models, Chemical; Oxidation-Reduction; Surface-Active Agents
PubMed: 28125349
DOI: 10.1146/annurev-food-030216-025812 -
Journal of Controlled Release :... Mar 2022The size of polymeric micelles crucially affects their tumor accumulation, penetration and antitumor efficacy. In the present study, micelles were formed based on...
The size of polymeric micelles crucially affects their tumor accumulation, penetration and antitumor efficacy. In the present study, micelles were formed based on amphiphilic poly(N-2-hydroxypropyl methacrylamide)-block-poly(N-2-benzoyloxypropyl methacrylamide) (p(HPMAm)-b-p(HPMAm-Bz)) via the solvent extraction method, and factors impacting micelle size were systematically studied, including the molecular weight of the polymers, homopolymer content, and processing methods (i.e., batch process versus continuous microfluidics). The formation of core-shell structured micelles was demonstrated by light scattering, sedimentation velocity and electron microscopy analysis. Micellar size and aggregation number increased with decreasing the molecular weight ratio of the hydrophilic/hydrophobic block. The presence of hydrophobic p(HPMAm-Bz) homopolymer and high copolymer concentration increased micelle size, while the presence of hydrophilic p(HPMAm) homopolymer did not affect micellar size. Regarding processing conditions, it was found that the use of tetrahydrofuran and acetone as solvents for the polymers resulted in larger micelles, likely due to their relatively high water-solvent interaction parameters as compared to other solvents tested, i.e., dimethylformamide, dimethylacetamide, and dimethyl sulfoxide. Among the latter, only dimethylformamide led to micelles with a narrow polydispersity. Addition of dimethylformamide to an aqueous solvent and faster mixing of two solvents using microfluidics favored the formation of smaller micelles. In conclusion, our results show that the size of all-HPMA polymeric micelles can be easily tailored from 40 to 120 nm by varying the formulation properties and processing parameters.
Topics: Dimethylformamide; Methacrylates; Micelles; Polyethylene Glycols; Polymers; Solvents
PubMed: 35104571
DOI: 10.1016/j.jconrel.2022.01.042 -
Biomedicine & Pharmacotherapy =... Mar 2024Interest in multifunctional polymer nanoparticles for targeted delivery of anti-cancer drugs has grown significantly in recent years. In this study, tumor-targeting...
Interest in multifunctional polymer nanoparticles for targeted delivery of anti-cancer drugs has grown significantly in recent years. In this study, tumor-targeting echogenic polymer micelles were prepared from poly(ethylene glycol) methyl ether-alkyl carbonate (mPEG-AC) derivatives, and their potential in cancer therapy was assessed. Various mPEG derivatives with carbonate linkages were synthesized via an alkyl halide reaction between mPEG and alkyl chloroformate. Micelle formation using polymer amphiphiles in aqueous media and the subsequent carbon dioxide (CO) gas generation from the micelles was confirmed. Their ability to target neuroblastoma was substantially enhanced by incorporating the rabies virus glycoprotein (RVG) peptide. RVG-modified gas-generating micelles significantly inhibited tumor growth in a tumor-bearing mouse model owing to CO gas generation within tumor cells and resultant cytolytic effects, showing minimal side effects. The development of multifunctional polymer micelles may offer a promising therapeutic approach for various diseases, including cancer.
Topics: Animals; Mice; Polymers; Micelles; Carbon Dioxide; Polyethylene Glycols; Neuroblastoma; Peptides; Carbonates; Formates
PubMed: 38354570
DOI: 10.1016/j.biopha.2024.116272 -
Biomacromolecules Jun 2023Self-sorting in functionalized dipeptide systems can be driven by the chirality of a single amino acid, both at a high pH in the micellar state and at a low pH in the...
Self-sorting in functionalized dipeptide systems can be driven by the chirality of a single amino acid, both at a high pH in the micellar state and at a low pH in the gel state. The structures formed are affected to some degree by the relative concentrations of each component showing the complexity of such an approach. The structures underpinning the gel network are predefined by the micellar structures at a high pH. Here, we describe the systems prepared from two dipeptide-based gelators that differ only by the chirality of one of the amino acids. We provide firm evidence for self-sorting in the micellar and gel phases using small-angle neutron scattering and cryo-transmission electron microscopy (cryo-TEM), showing that complete self-sorting occurs across a range of relative concentrations.
Topics: Dipeptides; Microscopy, Electron, Transmission; Micelles; Cryoelectron Microscopy; Amino Acids
PubMed: 37257089
DOI: 10.1021/acs.biomac.3c00246 -
CPT: Pharmacometrics & Systems... May 2023Although single-dose ivermectin has been widely used in mass-drug administration programs for onchocerciasis and lymphatic filariasis for many years, ivermectin may have... (Review)
Review
Although single-dose ivermectin has been widely used in mass-drug administration programs for onchocerciasis and lymphatic filariasis for many years, ivermectin may have utility as an endectocide with mosquito-lethal effects at dosages greater and longer than those used to treat helminths. The final physiologically-based pharmacokinetic (PBPK) model for ivermectin described here was able to capture, with reasonable accuracy, observed plasma drug concentration-time profiles and exposures of ivermectin after a single oral dose of the drug in healthy male (dose range 6-30 mg) and female subjects, in both fasted and fed states, in African patients with onchocerciasis (150 μg/kg) and in African children. The PBPK model can be used for further work on lactation, pediatric dosing (considering CYP3A4 and Pg-p ontogenies), and pregnancy, especially if nonstandard doses will be used. The key findings of our study indicate that absorption of ivermectin may be highly dependent on bile micelle-mediated solubility. The drug is highly lipophilic and permeable, and its plasma exposure appears to be associated with the body mass index of an individual. These are all factors that need to be considered when extrapolating to more complex oral formulations or alternative routes of administration. Administering lower doses over a longer period may attenuate the dependence on bile micelle-mediated solubility. With relevant inputs, the verified PBPK model developed here could be used to simulate plasma exposures following administration of ivermectin by complex generics in development.
Topics: Animals; Humans; Male; Female; Child; Ivermectin; Onchocerciasis; Micelles; Administration, Oral; Models, Biological
PubMed: 36840414
DOI: 10.1002/psp4.12950 -
The Journal of Physical Chemistry. B Jun 2015Several membrane proteins and numerous membrane-active peptides have been studied in detergent micelles by solution NMR. However, the detailed structure of these...
Several membrane proteins and numerous membrane-active peptides have been studied in detergent micelles by solution NMR. However, the detailed structure of these complexes remains unknown. We propose a modeling approach that treats the protein and detergent in atomistic detail and the solvent implicitly. The model is based on previous work on dodecylphosphocholine micelles, adapted for use with the CHARMM36 force field and extended to sodium dodecyl sulfate micelles. Solvation parameters were slightly adjusted to reproduce experimental data on aggregation numbers and critical micelle concentrations. To test the approach, several membrane-active peptides and three β-barrel membrane proteins were subjected to molecular dynamics simulations in the presence of a large number of detergent molecules. Their experimentally determined secondary structure was maintained and the RMSD values were less than 2 Å. Deformations were commonly observed in the N or C termini. The atomistic view of the protein-micelle systems that this approach provides could be useful in interpreting biophysical experiments carried out in the presence of detergent.
Topics: Detergents; Micelles; Molecular Dynamics Simulation; Nuclear Magnetic Resonance, Biomolecular; Phosphorylcholine; Protein Multimerization; Protein Structure, Secondary; Proteins; Sodium Dodecyl Sulfate; Solvents; Water
PubMed: 26035001
DOI: 10.1021/acs.jpcb.5b00171