Elucidation of Spatial Distribution of Hydrophobic Aromatic Compounds Encapsulated in Polymer Micelles by Anomalous Small-Angle X-ray Scattering

Sasaki, Shota; Machida, Ginpei; Nakanishi, Ryosuke; Kinoshita, Masaki; Akiba, Isamu

doi:10.3390/polym10020180

Cited by 6 publications

(4 citation statements)

References 17 publications

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“…The utilization of a conventional two-phase sphere modeling approach could not fully realize the micellar structure with high precision. There were more reports utilizing a two-phase sphere modeling approach [32,33,34] but the outcomes of the analyses were faced with a reoccurring lack of precision. Recently, a more quantitative analysis based on a three-phase ellipsoid modeling approach was introduced to examine polymer micelles [35].…”

Section: Introductionmentioning

confidence: 99%

Micelle Structure Details and Stabilities of Cyclic Block Copolymer Amphiphile and Its Linear Analogues

2019

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In this study, we investigate structures and stabilities of the micelles of a cyclic amphiphile (c-PBA-b-PEO) composed of poly(-n-butyl acrylate) (PBA) and poly(ethylene oxide) (PEO) blocks and its linear diblock and triblock analogues (l-PBA-b-PEO and -l-PBA--b-PEO-b-PBA) by using synchrotron X-ray scattering and quantitative data analysis. The comprehensive scattering analysis gives details and insights to the micellar architecture through structural parameters. Furthermore, this analysis provides direct clues for structural stabilities in micelles, which can be used as a good guideline to design highly stable micelles. Interestingly, in water, all topological polymers are found to form ellipsoidal micelles rather than spherical micelles; more interestingly, the cyclic polymer and its linear triblock analog make oblate-ellipsoidal micelles while the linear diblock analog makes a prolate-ellipsoidal micelle. The analysis results collectively inform that the cyclic topology enables more compact micelle formation as well as provides a positive impact on the micellar structural integrity.

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Section: Introductionmentioning

confidence: 99%

Micelle Structure Details and Stabilities of Cyclic Block Copolymer Amphiphile and Its Linear Analogues

2019

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“…The varying temperatures may affect sol-gel transition but did not correspond with the viscosity and rheology of the polymeric micelles in FPM7 and FPM8 ( Figure 2 B). Hydrophilic or amphiphilic block copolymers (such as P407 and SPA) undergo self-assembly into polymeric micelles, with insoluble drugs [ 7 ] inside a hydrophobic core, surrounded by hydrate shell layers [ 30 ]. Sol-gel transition did not occur due to the character of the polymeric micelles and concentration of polymers in FPM7 and FPM8.…”

Section: Resultsmentioning

confidence: 99%

Polymeric Micelles Enhance Mucosal Contact Time and Deposition of Fluocinolone Acetonide

et al. 2022

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This study used polymeric micelles to improve quality by increasing drug solubility, extending mucosal drug retention time, enhancing mucoadhesiveness, and promoting drug permeation and deposition. Fluocinolone acetonide (FA) was loaded into polymeric micelles (FPM), which were composed of poloxamer 407 (P407), sodium polyacrylate (SPA), and polyethylene glycol 400, and their physicochemical properties were examined. Small-angle X-ray scattering (SAXS) revealed a hexagonal micellar structure at all temperatures, and the concentrations of P407 and SPA were shown to significantly affect the solubility, mucoadhesion, release, and permeation of FPMs. The characteristics of FPM7 and FPM8 revealed crystalline states inside the micelles, which was consistent with the morphology and nano-hexagonal structure. The results of ex vivo experiments using focal plane array (FPA)-based Fourier transform infrared (FTIR) imaging showed that FPM7 penetrated quickly through the epithelium, lamina propria, and submucosa, and remained in all layers from 5–30 min following administration. In contrast, FPM8 penetrated and passed through all layers. FPMs with extended mucoadhesion, improved drug–mucosal retention time, and increased FA permeation and deposition were successfully developed, and could be a promising innovation for increasing the efficiency of mouth rinses, as well as other topical pharmaceutical and dental applications.

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“…It can dramatically affect many characteristics, for instance, the extent of solubilization, the drug-loading stability, and the release kinetics of the encapsulated drugs in the delivery systems. 1,2 On the basis of many experimental methodologies, such as UV absorption spectroscopy, 3 nuclear magnetic resonance (NMR), 4 smallangle X-ray 5,6 or neutron scattering, 7 and theoretical considerations, 1 it has been proposed that the hydrophobic core of the micelles serves as a solubilization location of hydrophobic drugs most of the time, and sometimes the palisade region. However, it is noteworthy that all studies described above are focused on the single micellar system composed of a single polymer (PMs), which are not suitable for polymeric mixed micellar systems (PMMs), composed of amphiphilic polymers or polymer surfactants, which can realize functional synergism and higher solubilization capacity, improved stability, and better-controlled drug release performance, superior to the individual component.…”

Section: ■ Introductionmentioning

confidence: 99%

“…In recent years, there has been significant interest in the solubilization region within polymer micelles, which is expected to be of key importance. It can dramatically affect many characteristics, for instance, the extent of solubilization, the drug-loading stability, and the release kinetics of the encapsulated drugs in the delivery systems. , On the basis of many experimental methodologies, such as UV absorption spectroscopy, nuclear magnetic resonance (NMR), small-angle X-ray , or neutron scattering, and theoretical considerations, it has been proposed that the hydrophobic core of the micelles serves as a solubilization location of hydrophobic drugs most of the time, and sometimes the palisade region.…”

Section: Introductionmentioning

confidence: 99%

Understanding the Synergistic Correlation between the Spatial Distribution of Drug-Loaded Mixed Micellar Systems and In Vitro Behavior via Experimental and Computational Approaches

et al. 2021

Mol. Pharmaceutics

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To better promote the application of polymeric mixed micelles (PMMs), a coarse-grained molecular dynamics simulation (CGMD) has been employed to investigate the factors controlling the spatial distribution within the PMMs and predict their drug-loading properties, meanwhile, combined with experimental methods to validate and examine it. In this study, the snapshots obtained from CGMD and the results of proton nuclear magnetic resonance (1H NMR) and transmission electron microscopy (TEM) provide new insights into the distribution principle that the spatial distribution depends on the hydrophobic compatibility of drugs with the regions within PMMs. Docetaxel (DTX) is located within the interior or near the core–corona interface of the HS15 hydrophobic core inside FS/PMMs (PMMs fabricated from a nonionic triblock copolymer (F127)) and a nonionic surfactant (HS15), and therefore, the system with a high HS15 ratio, such as system I, is more suitable for loading DTX. In contrast, the more water-soluble puerarin (PUE) is more likely to be solubilized in the “secondary hydrophobic area,” mainly formed by the hydrophobic part of F127 within FS/PMMs. However, when the initial feeding concentration of the drug is increased or the FS mixing ratios are changed, an inappropriate distribution would occur and hence influence the drug-loading stability. Also, this impact was further elucidated by the calculated parameters (solvent-accessible surface area (SASA), the radius of gyration (R g), and energy landscape), and the analysis of the drug leakage, concluding that inappropriate distribution of the drug would lower the stability of the drug in the PMMs. These results combined together provide new insights into the distribution principle that the spatial distribution of drugs within PMMs depends on the hydrophobic compatibility of drugs with the regions formed by micellar materials. Additionally, in vitro drug release yielded a consistent picture with the above conclusions and provides evidence that both the location of the drug within the systems and the stability of the drug-loading system have a great influence on the drug release behavior. Accordingly, this work demonstrates that we can tune the drug-loading stability and drug release behavior via the drug–PMM interaction and drug location study, and CGMD technology would be a step forward in the search for suitable drug-delivery PMMs.

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Elucidation of Spatial Distribution of Hydrophobic Aromatic Compounds Encapsulated in Polymer Micelles by Anomalous Small-Angle X-ray Scattering

Cited by 6 publications

References 17 publications

Micelle Structure Details and Stabilities of Cyclic Block Copolymer Amphiphile and Its Linear Analogues

Micelle Structure Details and Stabilities of Cyclic Block Copolymer Amphiphile and Its Linear Analogues

Polymeric Micelles Enhance Mucosal Contact Time and Deposition of Fluocinolone Acetonide

Understanding the Synergistic Correlation between the Spatial Distribution of Drug-Loaded Mixed Micellar Systems and In Vitro Behavior via Experimental and Computational Approaches

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