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The article discusses how the effectiveness of oncotherapy is hindered by tumor heterogeneities, highlighting the need to understand spatial interactions between tumors and nanoparticles. Topics include the resolution of tumor-nanoparticle interactions, multidimensional correlations, and accurate assessment of drug delivery systems.

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. The significant reduction in vasculature and degeneration of neurons in the thoracic spinal cord visualized via SRμCT after chronic compression were consistent with the changes detected by immunofluorescence staining. The 3D morphological measurements revealed significant reductions of neurovascular parameters in the thoracic spinal cord after 1 month of compression and became even worse after 6 months without relief of compression. In addition, the distinct 3D morphological twist and the decrease in branches of the central sulcal artery after chronic compression vividly displayed that these could be the potential triggers leading to blood flow reduction and neural deficits of the thoracic spinal cord. Our findings propose a novel methodology for the 3D analysis of neurovascular repair in chronic spinal cord compression, both qualitatively and quantitatively. The results indicated that compression simultaneously caused vascular dysfunction and neuronal network impairment, which should be acknowledged as concurrent events after chronic thoracic spinal cord injury. Combining neuroprotection with vasoprotection may provide promising therapeutic targets for chronic thoracic spinal cord compression. [ABSTRACT FROM AUTHOR]

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. The significant reduction in vasculature and degeneration of neurons in the thoracic spinal cord visualized via SRμCT after chronic compression were consistent with the changes detected by immunofluorescence staining. The 3D morphological measurements revealed significant reductions of neurovascular parameters in the thoracic spinal cord after 1 month of compression and became even worse after 6 months without relief of compression. In addition, the distinct 3D morphological twist and the decrease in branches of the central sulcal artery after chronic compression vividly displayed that these could be the potential triggers leading to blood flow reduction and neural deficits of the thoracic spinal cord. Our findings propose a novel methodology for the 3D analysis of neurovascular repair in chronic spinal cord compression, both qualitatively and quantitatively. The results indicated that compression simultaneously caused vascular dysfunction and neuronal network impairment, which should be acknowledged as concurrent events after chronic thoracic spinal cord injury. Combining neuroprotection with vasoprotection may provide promising therapeutic targets for chronic thoracic spinal cord compression. [ABSTRACT FROM AUTHOR]

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. The three-dimensional (3D) information of SA particles in tablets was detected by a quantitative and non-invasive 3D structure elucidation technique, namely, synchrotron radiation X-ray micro-computed tomography (SR-μCT). SA particles in glipizide tablets prepared by using unmodified SA (GUT), reprocessed SA (GRT), as well as reference listed drug (RLD) of glipizide tablets were analyzed by SR-μCT. The results showed that the reprocessed SA with better flowability contributed to similarity of breaking forces between that of GRT and RLD. SA particles in GRT were very similar to those in RLD with uniform morphology and particle size, while SA particles in GUT were not evenly distributed. These findings not only demonstrated the feasibility of SR-μCT as a new method in revealing the morphology and spatial distribution of excipient in drug delivery system, but also deepened insights of solid dosage form design into a new scale by powder engineering. [ABSTRACT FROM AUTHOR]

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. It was found that the microstructure and morphology of the microspheres were significantly influenced by preparation processes as the primary factors to determine the release profiles and taste-masking effects. The sphericity of ibuprofen microspheres congealed in citric acid solution was higher than that of other two and its morphology was more regular than that being congealed in air or distilled water, and the contact angles between congealing media and melted ibuprofen in octadecanol and glycerin monostearate well demonstrated the structure differences among microspheres of three processes which controlled the release characteristics of the microspheres. The structure parameters like porosity, sphericity, and radius ratio from quantitative analysis were correlated well with drug release behaviors. The results demonstrated that the exterior morphology and internal structure of microspheres had considerable influences on the drug release behaviors as well as taste-masking effects. [ABSTRACT FROM AUTHOR]

ABSTRACT: One unusual and challenging scientific field that has received only cursory attention to date is the threedimensional (3D) microstructure and spatial distribution of drug(s) and formulation materials in solid dosage forms. This study aims to provide deeper insight into the relationships between the microstructure of multiple-unit pellet system (MUPS) tablets and the spatial distribution of the active pharmaceutical ingredient (API) and excipients to facilitate the design of quantitative models for drug delivery systems. Synchrotron radiation X-ray microcomputed tomography (SR-μCT) was established as a 3D structure elucidation technique, which, in conjunction with liquid chromatography coupled to mass spectrometry (LC-MS) or liquid chromatography with evaporative light-scattering detector (LC-ELSD) enables chemical analysis of tablets. On the basis of the specific interior construction of theophylline MUPS tablets, the spatial distribution of materials was acquired by quantifying microregion samples that had been validated by SR-μCT for their locations in the MUPS tablets. The 3D structure of the MUPS tablets was catalogued as three structural domains: a matrix layer (ML), a protective cushion layer (PCL), and pellets (PL). Compared with the components in the ML, components in the PL had a larger proportion of theophylline, sucrose, and diethyl phthalate and a smaller proportion of lactose and sodium lauryl sulfate, whereas glyceryl monostearate was found to account for a large portion of the PCL. Microstructural characterization-guided zonal chemical determination represents a new approach for quality assessment and the development of drug delivery systems with in-depth insight into their constituent layers on a new scale. [ABSTRACT FROM AUTHOR]

This study investigated the formulation mechanism of microspheres via internal surfactant distribution. Eudragit L100 based microspheres loaded with bovine serum albumin were prepared by solid in oil in oil emulsion solvent evaporation method using acetone and liquid paraffin system containing sucrose stearate as a surfactant. The fabricated microspheres were evaluated for encapsulation efficiency, particle size, production yield, and in vitro release characteristics. The internal structures of microspheres were characterized using synchrotron radiation X-ray microcomputed tomography (SR-µCT). The enhanced contrast made the sucrose stearate distinguished from Eudragit to have its three dimensional (3D) distribution. Results indicated that the content and concentration determined the state of sucrose stearate and had significant influences on the release kinetics of protein. The dispersity of sucrose stearate was the primary factor that controlled the structure of the microspheres and further affected the encapsulation efficiency, effective drug loading, as well as in vitro release behavior. In conclusion, the 3D internal distribution of surfactant in microspheres and its effects on protein release behaviors have been revealed for the first time. The highly resolved 3D architecture provides new evidence for the deep understanding of the microsphere formation mechanism. [ABSTRACT FROM AUTHOR]

The control of supramolecular systems requires a thorough understanding of their dynamics, especially on a molecular level. It is extremely difficult to determine the thermokinetic parameters of supramolecular systems, such as drug-cyclodextrin complexes with fast association/dissociation processes by experimental techniques. In this paper, molecular modeling combined with novel mathematical relationships integrating the thermodynamic/thermokinetic parameters of a series of isomeric multiconfigurations to predict the overall parameters in a range of pH values have been employed to study supramolecular dynamics at the molecular level. A suitable form of Eyring's equation was derived and a two-stage model was introduced. The new approach enabled accurate prediction of the apparent dissociation/association (koff/kon) and unbinding/binding (k-r/kr) rate constants of the ubiquitous multiconfiguration complexes of the supramolecular system. The pyronine Y (PY) was used as a model system for the validation of the presented method. Interestingly, the predicted koff value ((40 ± 1) x 105 s-1, 298 K) of PY is largely in agreement with that previously determined by fluorescence correlation spectroscopy ((5 ± 3) x 105 s-1, 298 K). Moreover, the koff/kon and k-r/kr for flurbiprofen-β-cylcodextrin and ibuprofen-β-cyclodextrin systems were also predicted and suggested that the association processes are diffusion-controlled. The methodology is considered to be especially useful in the design and selection of excipients for a supramolecular system with preferred association and dissociation rate constants and understanding their mechanisms. It is believed that this new approach could be applicable to a wide range of ligand-receptor supramolecular systems and will surely help in understanding their complex mechanism. [ABSTRACT FROM AUTHOR]