"3D channel maze" to control drug release from multiple unit tablets.

Diffusion is defined as general mechanism for drug release from advanced delivery systems, yet dynamic structure of dosage form intrinsically plays an unknown role. The synchrotron radiation X-ray micro-computed tomography (SR-μCT) three-dimensional (3D) imaging and in-depth analysis of 3D structures were applied to readily differentiate materials and accurately capture internal structure changes of multiple unit pellet system (MUPS) and the constituent pellets, visualizing internal 3D structure of a MUPS of theophylline tablets for their 3 levels hierarchy structures: pellets with rapid drug release characteristics, a protective cushion layer and a matrix layer. Drug release pathways were extracted from SR-μCT images and a 3D maze network was constructed using pore network analysis to quantify the internal structural evolution during drug release.

Advances in Structure Pharmaceutics from Discovery to Evaluation and Design.

Drug delivery systems (DDSs) play an important role in delivering active pharmaceutical ingredients (APIs) to targeted sites with a predesigned release pattern. The chemical and biological properties of APIs and excipients have been extensively studied for their contribution to DDS quality and effectiveness; however, the structural characteristics of DDSs have not been adequately explored. Structure pharmaceutics involves the study of the structure of DDSs, especially the three-dimensional (3D) structures, and its interaction with the physiological and pathological structure of organisms, possibly influencing their release kinetics and targeting abilities.

Cross-scale tracing of nanoparticles and tumors at the single-cell level using the whole-lung atlas.

Currently, the effectiveness of oncotherapy is limited by tumor heterogeneities, which presents a huge challenge for the development of nanotargeted drug delivery systems (DDSs). Therefore, it is important to resolve the spatiotemporal interactions between tumors and nanoparticles. However, targeting evaluation has been limited by particle visualization due to the gap between whole-organ scale and subcellular precision.

Chrysanthemum sporopollenin: A novel vaccine delivery system for nasal mucosal immunity.

Objective: Mucosal immunization was an effective defender against pathogens. Nasal vaccines could activate both systemic and mucosal immunity to trigger protective immune responses. However, due to the weak immunogenicity of nasal vaccines and the lack of appropriate antigen carriers, very few nasal vaccines have been clinically approved for human use, which was a major barrier to the development of nasal vaccines.

IL-4-loaded alginate/chitosan multilayer films for promoting angiogenesis through both direct and indirect means.

Vascularization remains a major challenge in tissue engineering. In tissue repair with the involvement of biomaterials, both the material properties and material-induced immune response can affect angiogenesis. However, there is a scarcity of research on biomaterials that modulate angiogenesis simultaneously from both perspectives.

Structural and functional imaging of brains.

Analyzing the complex structures and functions of brain is the key issue to understanding the physiological and pathological processes. Although neuronal morphology and local distribution of neurons/blood vessels in the brain have been known, the subcellular structures of cells remain challenging, especially in the live brain. In addition, the complicated brain functions involve numerous functional molecules, but the concentrations, distributions and interactions of these molecules in the brain are still poorly understood.

Three-Dimensional Quantitative Coherent Diffraction Imaging of Treated with Peptide-Mineralized Au-Cluster Probes.

Characterizing interactions between microbial cells and their specific inhibitory drugs is essential for developing effective drugs and understanding the therapeutic mechanism. Functional metal nanoclusters can be effective inhibitory agents against microorganisms according to various characterization methods, but quantitative three-dimensional (3D) spatial structural analysis of intact cells is lacking. Herein, using coherent X-ray diffraction imaging, we performed in situ 3D visualization of unstained cells treated with peptide-mineralized Au-cluster probes at a resolution of ∼47 nm.

Redefinition to bilayer osmotic pump tablets as subterranean river system within mini-earth three-dimensional structure mechanism.

Defining and visualizing the three-dimensional (3D) structures of pharmaceuticals provides a new and important tool to elucidate the phenomenal behavior and underlying mechanisms of drug delivery systems. The mechanism of drug release from complex structured dosage forms, such as bilayer osmotic pump tablets, has not been investigated widely for most solid 3D structures. In this study, bilayer osmotic pump tablets undergoing dissolution, as well as after dissolution in a desiccated solid state were examined, and visualized by synchrotron radiation micro-computed tomography (SR-μCT).

High-Resolution Digital Panorama of Multiple Structures in Whole Brain of Alzheimer's Disease Mice.

Simultaneously visualizing Amyloid-β (Aβ) plaque with its surrounding brain structures at the subcellular level in the intact brain is essential for understanding the complex pathology of Alzheimer's disease, but is still rarely achieved due to the technical limitations. Combining the micro-optical sectioning tomography (MOST) system, whole-brain Nissl staining, and customized image processing workflow, we generated a whole-brain panorama of Alzheimer's disease mice without specific labeling. The workflow employed the steps that include virtual channel splitting, feature enhancement, iso-surface rendering, direct volume rendering, and feature fusion to extract and reconstruct the different signals with distinct gray values and morphologies.

Bridging the structure gap between pellets in artificial dissolution media and in gastro-intestinal tract in rats.

Changes in structure of oral solid dosage forms (OSDF) elementally determine the drug release and its therapeutic effects. In this research, synchrotron radiation X-ray micro-computed tomography was utilized to visualize the 3D structure of enteric coated pellets recovered from the gastrointestinal tract of rats. The structures of pellets in solid state and compendium media were measured.

Multiscale modelling of cerebrovascular injury reveals the role of vascular anatomy and parenchymal shear stresses.

Neurovascular injury is often observed in traumatic brain injury (TBI). However, the relationship between mechanical forces and vascular injury is still unclear. A key question is whether the complex anatomy of vasculature plays a role in increasing forces in cerebral vessels and producing damage.

Simultaneous 3D Visualization of the Microvascular and Neural Network in Mouse Spinal Cord Using Synchrotron Radiation Micro-Computed Tomography.

Effective methods for visualizing neurovascular morphology are essential for understanding the normal spinal cord and the morphological alterations associated with diseases. However, ideal techniques for simultaneously imaging neurovascular structure in a broad region of a specimen are still lacking. In this study, we combined Golgi staining with angiography and synchrotron radiation micro-computed tomography (SRμCT) to visualize the 3D neurovascular network in the mouse spinal cord.

Alginate/chitosan modified immunomodulatory titanium implants for promoting osteogenesis in vitro and in vivo.

The essentiality of macrophages for biomaterial-mediated osteogenesis has been increasingly recognized. However, it is still unclear what is the specific role and molecular mechanisms of macrophages and material properties in the regulation of osteogenesis. As an interdisciplinary field exploring the cross-talk between immune and skeletal systems, osteoimmunology has shifted the perspective of bone substitute materials from immunosuppressive materials to immunomodulatory materials.

Multiscale Co-reconstruction of Lung Architectures and Inhalable Materials Spatial Distribution.

The effective pulmonary deposition of inhaled particulate carriers loaded with drugs is a prerequisite for therapeutic effects of drug delivery via inhalation route. Revealing the sophisticated lung scaffold and intrapulmonary distribution of particles at three-dimensional (3D), in-situ, and single-particle level remains a fundamental and critical challenge for dry powder inhalation in pre-clinical research. Here, taking advantage of the micro optical sectioning tomography system, the high-precision cross-scale visualization of entire lung anatomy is obtained.

A combinatorial method to visualize the neuronal network in the mouse spinal cord: combination of a modified Golgi-Cox method and synchrotron radiation micro-computed tomography.

Exploring the three-dimensional (3D) morphology of neurons is essential to understanding spinal cord function and associated diseases comprehensively. However, 3D imaging of the neuronal network in the broad region of the spinal cord at cellular resolution remains a challenge in the field of neuroscience. In this study, to obtain high-resolution 3D imaging of a detailed neuronal network in the mass of the spinal cord, the combination of synchrotron radiation micro-computed tomography (SRμCT) and the Golgi-cox staining were used.

Dynamic structure model of polyelectrolyte complex based controlled-release matrix tablets visualized by synchrotron radiation micro-computed tomography.

Hydrophilic matrix tablets are the most commonly used dosage forms to fabricate oral controlled-release systems. It is highly desirable to design delivery system with novel mechanism to achieve sustained drug release through a simplified preparation process. The chitosan-anionic polymers based matrix tablets is assumed to produce self-assembly in the gastrointestinal tract, then transferring into film-coated tablets from original matrix type.

SRμCT Reveals 3D Microstructural Alterations of the Vascular and Neuronal Network in a Rat Model of Chronic Compressive Thoracic Spinal Cord Injury.

The complex pathology of chronic thoracic spinal cord compression involves vascular and neuroarchitectural repair processes that are still largely unknown. In this study, we used synchrotron radiation microtomography (SRμCT) to quantitatively characterize the 3D temporal-spatial changes in the vascular and neuronal network after chronic thoracic spinal cord compression in order to obtain further insights into the pathogenesis of this disease and to elucidate its underlying mechanisms. Direct 3D characterization of the spinal cord microvasculature and neural microstructure of the thoracic spinal cord was successfully reconstructed.

Static and dynamic structural features of single pellets determine the release behaviors of metoprolol succinate sustained-release tablets.

The multiple-unit sustained-release (MUSR) dosage forms containing numerous sustained-release subunits present a reliable choice for oral formulation of controlled release systems. As a typical MUSR, the metoprolol succinate sustained-release tablet is an advanced system with limited researches devoted to relating its structure to the drug release phase other than the preparation process and modulation to the release behaviors. This research details a three-dimension method to image the internal structure and detail drug release features of commercial metoprolol succinate sustained-release tablets and component individual single pellets.

Multi-dimensional visualization for the morphology of lubricant stearic acid particles and their distribution in tablets.

The shapes of particles and their distribution in tablets, controlled by pretreatment and tableting process, determine the pharmaceutical performance of excipient like lubricant. This study aims to provide deeper insights to the relationship of the morphology and spatial distribution of stearic acid (SA) with the lubrication efficiency, as well as the resulting tablet property. Unmodified SA particles as flat sheet-like particles were firstly reprocessed by emulsification in hot water to obtain the reprocessed SA particles with spherical morphology.

Optimization of taste-masking on ibuprofen microspheres with selected structure features.

The microsphere was a primary particulate system for taste-masking with unique structural features defined by production process. In this article, ibuprofen lipid microspheres of octadecanol and glycerin monostearate were prepared to mask the undesirable taste of ibuprofen via three kinds of spray congealing processes, namely, air-cooling, water-cooling and citric acid solution-cooling. The stereoscopic and internal structures of ibuprofen microspheres were quantitatively analyzed by synchrotron radiation X-ray micro-computed tomography (SR-µCT) to establish the relationship between the preparation process and microsphere architectures.

Synchrotron Radiation-Based Three-Dimensional Visualization of Angioarchitectural Remodeling in Hippocampus of Epileptic Rats.

Characterizing the three-dimensional (3D) morphological alterations of microvessels under both normal and seizure conditions is crucial for a better understanding of epilepsy. However, conventional imaging techniques cannot detect microvessels on micron/sub-micron scales without angiography. In this study, synchrotron radiation (SR)-based X-ray in-line phase-contrast imaging (ILPCI) and quantitative 3D characterization were used to acquire high-resolution, high-contrast images of rat brain tissue under both normal and seizure conditions.

High-resolution mapping of brain vasculature and its impairment in the hippocampus of Alzheimer's disease mice.

Accumulating evidence indicates the critical importance of cerebrovascular dysfunction in the pathogenesis of Alzheimer's disease (AD). However, systematic comparative studies on the precise brain vasculature of wild-type and AD model mice are still rare. Using an image-optimization method for analysing Micro-Optical Sectioning Tomography (MOST) data, we generated cross-scale whole-brain 3D atlases that cover the entire vascular system from large vessels down to smallest capillaries at submicron resolution, for both wild-type mice and a transgenic (APP/PS1) mouse model of AD.

3D digital anatomic angioarchitecture of the mouse brain using synchrotron-radiation-based propagation phase-contrast imaging.

Thorough investigation of the three-dimensional (3D) configuration of the vasculature of mouse brain remains technologically difficult because of its complex anatomical structure. In this study, a systematic analysis is developed to visualize the 3D angioarchitecture of mouse brain at ultrahigh resolution using synchrotron-radiation-based propagation phase-contrast imaging. This method provides detailed restoration of the intricate brain microvascular network in a precise 3D manner.

Synchrotron radiation micro-tomography for high-resolution neurovascular network morphology investigation.

There has been increasing interest in using high-resolution micro-tomography to investigate the morphology of neurovascular networks in the central nervous system, which remain difficult to characterize due to their microscopic size as well as their delicate and complex 3D structure. Synchrotron radiation X-ray imaging, which has emerged as a cutting-edge imaging technology with a high spatial resolution, provides a novel platform for the non-destructive imaging of microvasculature networks at a sub-micrometre scale. When coupled with computed tomography, this technique allows the characterization of the 3D morphology of vasculature.