Efficient Strategy for Determining the Atomic-Resolution Structure of Micro- and Nanocrystalline Solids within Polymeric Microbeads: Domain-Edited NMR Crystallography

Precise structural analysis of multiphase polymeric nanocomposites remains a challenge even in the presence of high-quality X-ray diffraction data. This contribution thus addresses our attempt to formulate a combined analytical strategy for obtaining the atomic-resolution structure of multicomponent polymeric solids with complex nanodomain architecture. In this strategy, through the application of <i>T</i>₁-filtered solid-state NMR spectroscopy, the individual components are successively distinguished and selected, and the corresponding ¹H, ¹³C, and ¹⁵N isotropic chemical shifts are explicitly assigned. Thereafter, using an automated protocol allowing for processing and statistical analysis of large data sets, the experimentally determined NMR parameters are systematically compared with those DFT-calculated for the representative set of crystal structure predictions. Particular attention is devoted to the analysis of NMR parameters of hydrogen-bonded protons which are responsible for molecular packing. As a result of this search, the structures of micro- and nanosized crystallites dispersed in the polymeric matrix are determined and independently verified by the measurements of through-space dipolar couplings. The potential of this strategy is demonstrated on injectable polyanhydride microbeads consisting of a mixture of microcrystalline decitabine and nanocrystalline sebacic acid, both incorporated in the semicrystalline polymeric matrix of poly­(sebacic acid). Through the synergistic interplay between the measurements, calculations, and the statistical analysis, we have developed an integrated approach providing structural information that is challenging to elucidate using conventional diffraction approaches. This combination of experimental and theoretical approaches enables one to determine the structural arrangements of molecules in situations which are not tractable by conventional spectroscopic techniques

Structural Diversity of Solid Dispersions of Acetylsalicylic Acid As Seen by Solid-State NMR

Solid dispersions of active pharmaceutical ingredients are of increasing interest due to their versatile use. In the present study polyvinylpyrrolidone (PVP), poly­[<i>N</i>-(2-hydroxypropyl)-metacrylamide] (pHPMA), poly­(2-ethyl-2-oxazoline) (PEOx), and polyethylene glycol (PEG), each in three <i>M</i>_w, were used to demonstrate structural diversity of solid dispersions. Acetylsalicylic acid (ASA) was used as a model drug. Four distinct types of the solid dispersions of ASA were created using a freeze-drying method: (i) crystalline solid dispersions containing nanocrystalline ASA in a crystalline PEG matrix; (ii) amorphous glass suspensions with large ASA crystallites embedded in amorphous pHPMA; (iii) solid solutions with molecularly dispersed ASA in rigid amorphous PVP; and (iv) nanoheterogeneous solid solutions/suspensions containing nanosized ASA clusters dispersed in a semiflexible matrix of PEOx. The obtained structural data confirmed that the type of solid dispersion can be primarily controlled by the chemical constitutions of the applied polymers, while the molecular weight of the polymers had no detectable impact. The molecular structure of the prepared dispersions was characterized using solid-state NMR, wide-angle X-ray scattering (WAXS), and differential scanning calorimetry (DSC). By applying various ¹H–¹³C and ¹H–¹H correlation experiments combined with <i>T</i>₁(¹H) and <i>T</i>_1ρ(¹H) relaxation data, the extent of the molecular mixing was determined over a wide range of distances, from intimate intermolecular contacts (0.1–0.5 nm) up to the phase-separated nanodomains reaching ca. 500 nm. Hydrogen-bond interactions between ASA and polymers were probed by the analysis of ¹³C and ¹⁵N CP/MAS NMR spectra combined with the measurements of ¹H–¹⁵N dipolar profiles. Overall potentialities and limitations of individual experimental techniques were thoroughly evaluated

Polyelectrolyte pH-Responsive Protein-Containing Nanoparticles: The Physicochemical Supramolecular Approach

We report on the physicochemical properties and self-assembly behavior of novel efficient pH-sensitive nanocontainers based on the Food and Drug Administration-approved anionic polymer Eudragit L100-55 (poly­(methacrylic acid-co-ethyl acrylate) 1:1) and nonionic surfactant Brij98. The features of the interaction between Eudragit L100-55 and Brij98 at different pH values and their optimal ratio for nanoparticle formation were studied using isothermal titration calorimetry. The influence of the polymer-to-surfactant ratio on the size and structure of particles was studied at different pH values using dynamic light scattering and small-angle X-ray scattering methods. It was shown that stable nanoparticles are formed at acidic pH at polymer-to-surfactant molar ratios from 1:43 to 1:139. Trypsin was successfully encapsulated into Eudragit−Brij98 nanoparticles as a model bioactive component. The loading efficiency was determined by labeling trypsin with radioactive iodine-125. Eudragit−Brij98 nanoparticles effectively protected trypsin against pepsin digestion. The results showed that trypsin encapsulated into novel pH-sensitive nanocontainers retained more than 50% of its activity after treatment with pepsin compared with nonencapsulated trypsin. The described concept will contribute both to understanding the principles of and designing next-generation nanocontainers

Image-based visual hull of a tennis racket

Researchers are often interested in tracking object movement in sport. This could be useful to identify equipment designs that match the technique of players. Previously, stereo camera systems have been used to track markers attached to striking implements to measure their movement in three dimensions. However, manual selection of markers on the image plane can be time consuming and inaccurate. There is potential however to reduce these drawbacks associated with marker-based analysis by tracking a striking implement using its visual hull. The closest geometric approximation of an object that can be reconstructed using only its silhouette images is its visual hull. Early applications of visual hulls include size and shape estimation of objects such as stones. Recently, subject specific visual hulls constructed from multiple camera views combined with anatomical tracking algorithms have measured human motion through markerless motion capture. However, multiple camera systems are not practical for real play conditions in most sports. The application of visual hulls to measure movements of striking implements used in sport has not yet been explored. A set of calibrated views of a tennis racket were captured and segmented into binary images to obtain silhouettes. The visual hull of a tennis racket was constructed by intersection of the volume of space formed by back-projecting the silhouettes from all input views. This research is the first stage in the development of a system that measures movement of a striking implement in real play conditions by combining its visual hull with footage from a single camera

Study of Complex Thermosensitive Amphiphilic Polyoxazolines and Their Interaction with Ionic Surfactants. Are Hydrophobic, Thermosensitive, and Hydrophilic Moieties Equally Important?

The temperature-driven self-assembly of nonionic amphiphilic tailor-made triblock copolymers has been studied by DLS, NMR, ITC, and SAXS. The composition of these triblock copolymers is more complex than that of the vast majority of poly­(2-alkyl-2-oxazoline)­s: a statistical thermoresponsive (iPrOx) and hydrophobic (BuOx) central block with terminal hydrophilic blocks (MeOx). In general, as temperature increases, nanoparticles form in a process starting with single molecules that become loose aggregates and ends with the formation of compact nanoparticles. Here, we first attempt to resolve the effects of each block on nanoparticle formation. It has been proven that the iPrOx/MeOx ratio determines the value of the cloud point temperature, whereas the different BuOx–iPrOx blocks determine the character of the process. Finally, we complete our investigation by presenting the thermodynamic and structural profiles of the complexation between these triblock poly­(2-alkyl-2-oxazoline)­s and two ionic surfactants. The addition of an ionic surfactant promotes a rearrangement of the polymer molecules and the formation of complexes followed by the appearance of polymer–surfactant hybrid micelles. Analysis of the interaction shows a strong and nonspecific reaction between the polymers and the anionic surfactant sodium dodecyl sulfate and weak but polymer-state-sensitive interactions between the polymer and the cationic surfactant hexadecyltrimethylammonium bromide

Self-Assembly Thermodynamics of pH-Responsive Amino-Acid-Based Polymers with a Nonionic Surfactant

The behavior of pH-responsive polymers poly­(<i>N</i>-methacryloyl-l-valine) (P1), poly­(<i>N</i>-methacryloyl-l-phenylalanine) (P2), and poly­(<i>N</i>-methacryloylglycyne-l-leucine) (P3) has been studied in the presence of the nonionic surfactant Brij98. The pure polymers phase-separate in an acidic medium with critical pH_tr values of 3.7, 5.5, and 3.4, respectively. The addition of the surfactant prevents phase separation and promotes reorganization of polymer molecules. The nature of the interaction between polymer and surfactant depends on the amino acid structure in the side chain of the polymer. This effect was investigated by dynamic light scattering, isothermal titration calorimetry, electrophoretic measurements, small-angle neutron scattering, and infrared spectroscopy. Thermodynamic analysis revealed an endothermic association reaction in P1/Brij98 mixture, whereas a strong exothermic effect was observed for P2/Brij98 and P3/Brij98. Application of regular solution theory for the analysis of experimental enthalpograms indicated dominant hydrophobic interactions between P1 and Brij98 and specific interactions for the P2/Brij98 system. Electrophoretic and dynamic light scattering measurements support the applicability of the theory to these cases. The specific interactions can be ascribed to hydrogen bonds formed between the carboxylic groups of the polymer and the oligo­(ethylene oxide) head groups of the surfactant. Thus, differences in polymer–surfactant interactions between P1 and P2 polymers result in different structures of polymer–surfactant complexes. Specifically, small-angle neutron scattering revealed pearl-necklace complexes and “core–shell” structures for P1/Brij98 and P2/Brij98 systems, respectively. These results may help in the design of new pH-responsive site-specific micellar drug delivery systems or pH-responsive membrane-disrupting agents

Self-Assembled Thermoresponsive Polymeric Nanogels for ¹⁹F MR Imaging

Magnetic resonance imaging using fluorinated contrast agents (¹⁹F MRI) enables to achive highcontrast in images due to the negligible fluorine background in living tissues. In this pilot study, we developed new biocompatible, temperature-responsive, and easily synthesized polymeric nanogels containing a sufficient concentration of magnetically equivalent fluorine atoms for ¹⁹F MRI purposes. The structure of the nanogels is based on amphiphilic copolymers containing two blocks, a hydrophilic poly­[<i>N</i>-(2-hydroxypropyl)­methacrylamide] (PHPMA) or poly­(2-methyl-2-oxazoline) (PMeOx) block, and a thermoresponsive poly­[<i>N</i>(2,2difluoroethyl)­acrylamide] (PDFEA) block. The thermoresponsive properties of the PDFEA block allow us to control the process of nanogel self-assembly upon its heating in an aqueous solution. Particle size depends on the copolymer composition, and the most promising copolymers with longer thermoresponsive blocks form nanogels of suitable size for angiogenesis imaging or the labeling of cells (approximately 120 nm). The <i>in vitro</i> ¹⁹F MRI experiments reveal good sensitivity of the copolymer contrast agents, while the nanogels were proven to be noncytotoxic for several cell lines