Pluronic F68 Micelles as Carriers for an Anti-Inflammatory Drug: A Rheological and Scattering Investigation.

Age-long ambition of medical scientists has always been advancement in healthcare and therapeutic medicine. Biomedical research indeed claims paramount importance in nanomedicine and drug delivery, and the development of biocompatible storage structures for delivering drugs stands at the heart of emerging scientific works. The delivery of drugs into the human body is nevertheless a nontrivial and challenging task, and it is often addressed by using amphiphilic compounds as nanosized delivery vehicles. Pluronics belong to a peculiar class of biocompatible and thermosensitive nonionic amphiphilic copolymers, and their self-assemblies are employed as drug delivery excipients because of their unique properties. We herein report on the encapsulation of diclofenac sodium within Pluronic F68 self-assemblies in water, underpinning the impact of the drug on the rheological and microstructural evolution of pluronic-based systems. The self-assembly and thermoresponsive micellization were studied through isothermal steady rheological experiments at different temperatures on samples containing 45 wt % Pluronic F68 and different amounts of diclofenac sodium. The adoption of scattering techniques, small-angle X-ray scattering (SAXS) and small-angle neutron scattering (SANS), allowed for the description of the system features at the nanometer length scale, providing information about the characteristic size of each part of the micellar structures as a function of temperature and drug concentration. Diclofenac sodium is not a good fellow for Pluronic F68. The triblock copolymer aids the encapsulation of the drug, highly improving its water solubility, whereas diclofenac sodium somehow hinders Pluronic self-assembly. By using a simple empirical model and no fitting parameters, the steady viscosity can be predicted, although qualitatively, through the volume fraction of the micelles extracted through scattering techniques and compared to the rheological one. A tunable control of the viscous behavior of such biomedical systems may be achieved through the suitable choice of their composition.

Hierarchical Structure of Cellulose Nanofibril-Based Foams Explored by Multimodal X-ray Scattering.

Structural characterization techniques are fundamental to correlate the material macro-, nano-, and molecular-scale structures to their macroscopic properties and to engineer hierarchical materials. Here, we combine X-ray transmission with scanning small- and wide-angle X-ray scattering (sSWAXS) to investigate ultraporous and lightweight biopolymer-based foams using cellulose nanofibrils (CNFs) as building blocks. The power of multimodal sSWAXS for multiscale structural characterization of self-assembled CNFs is demonstrated by spatially resolved maps at the macroscale (foam density and porosity), at the nanoscale (foam structural compactness, CNF orientation in the foam walls, and CNF packing state), and at the molecular scale (cellulose crystallite dimensions). Specifically, we compare the impact of freeze-thawing-drying (FTD) fabrication steps, such as static/stirred freezing and thawing in ethanol/water, on foam structural hierarchy spanning from the molecular to the millimeter scale. As such, we demonstrate the potential of X-ray scattering imaging for hierarchical characterization of biopolymers.

Bioinspired Structural Hierarchy within Macroscopic Volumes of Synthetic Composites.

A key challenge in developing bioinspired composites is the fabrication of well-defined 3D hierarchical structures ranging from nano to the macroscale. Herein, the development of a synthetic polymer-apatite composite realized by integrating bottom-up self-assembly and additive manufacturing (AM) is described. The resulting composite exhibits a bioinspired hierarchical structure over its 3D macroscopic volume. The composite is assembled in a bottom-up manner, where periodic nanoscale assemblies of organic micellar fibrils and inorganic apatite nanocrystals are organized as bundles of mineralized microstructures. These microstructural bundles are preferentially oriented throughout the macroscopic volume of the material via extrusion based AM. The obtained structural hierarchy is investigated in 3D using electron microscopy and small angle X-ray scattering tensor tomography and correlated to the structural hierarchy and anisotropy observed in biological tissues such as bone and the bone-cartilage interface. This work demonstrates the possibility to form polymer-apatite composites with a well-defined hierarchical structure throughout its macroscopic volume, which is crucial for the development of mechanically optimized materials for applications such as bone and osteochondral implants.