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1.
Acta Pharmaceutica Sinica B ; (6): 2568-2577, 2022.
Artigo em Inglês | WPRIM | ID: wpr-929388

RESUMO

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). In situ formed 3D structures at different in vitro drug release states were characterized comprehensively. A distinct movement pattern of NaCl crystals from the push layer to the drug layer was observed, beneath the semi-permeable coating in the desiccated tablet samples. The 3D structures at different dissolution time revealed that the pushing upsurge in the bilayer osmotic pump tablet was directed via peripheral "roadways". Typically, different regions of the osmotic front, infiltration region, and dormant region were classified in the push layer during the dissolution of drug from tablet samples. According to the observed 3D microstructures, a "subterranean river model" for the drug release mechanism has been defined to explain the drug release mechanism.

2.
Acta Pharmaceutica Sinica B ; (6): 326-338, 2022.
Artigo em Inglês | WPRIM | ID: wpr-929297

RESUMO

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 in vitro compendium media were measured. Pellets in vivo underwent morphological and structural changes which differed significantly from those in vitro compendium media. Thus, optimizations of the dissolution media were performed to mimic the appropriate in vivo conditions by introducing pepsin and glass microspheres in media. The sphericity, pellet volume, pore volume and porosity of the in vivo esomeprazole magnesium pellets in stomach for 2 h were recorded 0.47, 1.55 × 108 μm3, 0.44 × 108 μm3 and 27.6%, respectively. After adding pepsin and glass microspheres, the above parameters in vitro reached to 0.44, 1.64 × 108 μm3, 0.38 × 108 μm3 and 23.0%, respectively. Omeprazole magnesium pellets behaved similarly. The structural features of pellets between in vitro media and in vivo condition were bridged successfully in terms of 3D structures to ensure better design, characterization and quality control of advanced OSDF.

3.
Acta Pharmaceutica Sinica ; (12): 1030-1034, 2020.
Artigo em Chinês | WPRIM | ID: wpr-821667

RESUMO

It is difficult to directly observe the structural transformation inside of soft capsules if their shells are opaque. This study was designed to noninvasively in situ measure the structural characteristics of the soft capsules and internal particle distributions to reveal the intrinsic quality of the soft capsules and develop a new technique for reverse engineering and the physical stability evaluation of the soft capsules. In this research, the CT projection images of soft capsules, namely, propolis soft capsules, were collected via synchrotron radiation X-ray micro computed tomography (SR-μCT). After three-dimensional reconstruction, the structural differences of the soft capsules under long-term test and accelerated test for 6 months were quantitatively analyzed by calculating the three-dimensional structure parameters such as volume, number and distribution of the particles inside and the thickness for the wall of the capsules. There were only a small number of particles evenly distributed in the soft capsules stored under common storage condition without layering. On the other hand, the shell wall of the soft capsule turned thinner locally at the occlusal portion and the particles with strong X-ray absorption were densely distributed at the edge of the capsule wall after the accelerated test. This study revealed that the structural parameters of soft capsules obtained by SR-μCT could be used to evaluate the influence of storage environment on the physical stability of soft capsules. The technology provides a new method for quality control and evaluation for the soft capsules.

4.
Chinese Medical Journal ; (24): 1959-1964, 2019.
Artigo em Inglês | WPRIM | ID: wpr-802777

RESUMO

Background@#Nickel-induced allergic contact dermatitis (Ni-ACD) is a global health problem. More detailed knowledge on the skin uptake of haptens is required. This study aimed to investigate the penetration process and distribution of nickel in skin tissues with late phase and early phase of Ni-ACD to understand the mechanisms of metal allergy.@*Methods@#Forty Hartley guinea pigs were divided into four groups according to the NiSO4 sensitizing concentration and the NiSO4 challenged concentration: the 5% NiSO4-group, 5% to 10% (sensitization-challenge; late phase group); 10% NiSO4-group, 10% to 10% (sensitization-challenge; early-phase group); and the positive and negative controls. Pathological biopsies were performed on each group. The depth profile of nickel element concentration in the skin of guinea pigs was detected by synchrotron radiation micro X-ray fluorescence spectroscopy (SR-μ-XRF) and micro X-ray absorption near-edge spectroscopy (μ-XANES).@*Results@#In each section, the nickel element concentration in both the 5% NiSO4-group and 10% NiSO4-group was significantly higher than that in the negative control group. In the upper 300-μm section of skin for the early phase group, the nickel element concentration was significantly higher than that in the lower section of skin. In deeper sections (<200 μm) of skin, the concentration of nickel in the early phase group was approximately equal to that in the late phase group. The curve of the late phase group was flat, which means that the nickel element concentration was distributed uniformly by SR-μ-XRF. According to the XANES data for the 10% NiSO4 metal salt solution, structural changes occurred in the skin model sample, indicating that nickel was not present in the Ni2+ aqueous ionic state but in the nickel-binding protein.@*Conclusions@#This study showed that the distribution of the nickel element concentration in ACD skin tissue was different between the early phase and late phase groups. The nickel element was not present in the Ni2+ aqueous ionic state but bound with certain proteins to form a complex in the stratum corneum in ACD model tissue.

5.
Acta Pharmaceutica Sinica ; (12): 291-296, 2018.
Artigo em Chinês | WPRIM | ID: wpr-779876

RESUMO

Beads, a novel drug delivery system self-assembled by cyclodextrins (CDs) and oil, has potential applications in the solidification of oil drugs and improving the bioavailability of lipid-soluble drugs. However, very few researches were dedicated to the mechanism of beads formation. In this study, three-dimensional structures of beads were visualized and investigated using synchrotron radiation X-ray microcomputed tomography (SR-μCT). The structural changes of beads attributed by drying process were analyzed and confirmed via visualization results of SR-μCT. Productively, it was proposed that Pickering emulsion droplets obtained during beads formation process were spatially localized orderly. Moreover, the effects of loading lipid soluble drug, namely, vitamin K1, on the structural changes of beads were also analyzed. It is well known that the surface tension of oil phase could be changed by the addition of lipid soluble constituents. It was reasonable that the three-dimensional structure of beads might be altered during the drug loading of vitamin K1 into the beads. However, although the morphologies of beads were changed to some extent, the ordered Pickering emulsion droplets during the process of beads formation was successfully illustrated based on the SR-μCT results. Conclusively, according to the three-dimensional structural analysis of the beads, this study revealed the organized architecture for Pickering emulsion droplet assembly and beads formation in cyclodextrin semi-inclusion complex, which significantly complements the formation mechanism of beads, and provides a structural basis for the further study of beads.

6.
Chinese Journal of Medical Imaging Technology ; (12): 171-175, 2018.
Artigo em Chinês | WPRIM | ID: wpr-706201

RESUMO

Objective To explore the feasibility of in vitro biological soft tissue imaging by using synchrotron radiation phase contrast CT.Methods Three samples of resected human cardia,two samples of resected human esophageal carcinoma and esophagus,as well as two samples of middle cerebral artery tissue extracted from corpses were fixed and airdried at room temperature for synchrotron radiation phase contrast CT imaging.The images of soft tissue structures were observed and compared with pathological findings.Results The images of synchrotron radiation phase contrast CT showed three-layer structure of cardia and esophagus,mucous,submucosa and muscular layer.The surface of mucous layer was smooth.The images of esophageal carcinoma showed cancerous tissue infiltrating esophageal wall.The wall and lumen of cerebral arteries could be also clearly displayed.Conclusion Synchrotron radiation phase contrast CT imaging can clearly display fine structures of in vitro biological soft tissue.

7.
Korean Journal of Physical Anthropology ; : 133-142, 2018.
Artigo em Coreano | WPRIM | ID: wpr-718962

RESUMO

3D histology is a imaging system for the 3D structural information of cells or tissues. The synchrotron radiation propagation phase contrast micro-CT has been used in 3D imaging methods. However, the simple phase contrast micro-CT did not give sufficient micro-structural information when the specimen contains soft elements, as is the case with many biomedical tissue samples. The purpose of this study is to develop a new technique to enhance the phase contrast effect for soft tissue imaging. Experiments were performed at the imaging beam lines of Pohang Accelerator Laboratory (PAL). The biomedical tissue samples under frozen state was mounted on a computer-controlled precision stage and rotated in 0.18° increments through 180°. An X-ray shadow of a specimen was converted into a visual image on the surface of a CdWO4 scintillator that was magnified using a microscopic objective lens (X5 or X20) before being captured with a digital CCD camera. 3-dimensional volume images of the specimen were obtained by applying a filtered back-projection algorithm to the projection images using a software package OCTOPUS. Surface reconstruction and volume segmentation and rendering were performed were performed using Amira software. In this study, We found that synchrotron phase contrast imaging of frozen tissue samples has higher contrast power for soft tissue than that of non-frozen samples. In conclusion, synchrotron radiation propagation phase contrast cryo-microCT imaging offers a promising tool for non-destructive high resolution 3D histology.


Assuntos
Octopodiformes , Síncrotrons
8.
Acta Pharmaceutica Sinica ; (12): 659-666, 2017.
Artigo em Chinês | WPRIM | ID: wpr-779643

RESUMO

Strategies and techniques are extremely important to improve the evaluation efficiency and fully guarantee the consistency of dosage forms. For preparations with a structural feature as solid dosage forms and particulate dispersion systems, the structures of dosage forms are the outcome of the specific formulation and production process, which determine the drug delivery behaviors as well as the pharmacokinetics of the dosage forms. Conventional techniques failed to quantitatively determine the structures of dosage forms. Synchrotron radiation micro-computed tomography is a new generation of structural quantitative characterization technology in revealing the internal structure of dosage forms with unprecedented capability for quantitative characterization of the static and dynamic structures of dosage forms, enabling to reversely analyze the production process and identify the structure differences between the generics and brand products. Based on synchrotron radiation micro-computed tomography methodology researches and applications in static structures (powders, particulate systems, tablets, films, membranes, etc.), dynamic structures (hydration) and de-formulation of production process, we have classified the structures of dosage forms into four levels from macro-scope to molecular level as dosage forms, granular intermediates for formulation, dynamic structure and molecular structures, and proposed dosage form structure based new strategy for consistency evaluation. Along with conventional dissolution/ release behavior similarity, the internal structure consistency ensures high consistency between the brand product and the generics.

9.
Acta Pharmaceutica Sinica ; (12): 985-2016.
Artigo em Chinês | WPRIM | ID: wpr-779267

RESUMO

Ibuprofen lipid pellets prepared by melting method could mask the bitter taste of the drug to some extent. The pellets were further coated with chitosan (cationic) and gelatin (anionic) by ionic interaction layerby- layer self-assembly (LBL) coating to improve masking effects. In this paper, the release percentage of drugs in short time (1 min) was utilized as an indicator for the taste-masking, and it had confirmed the LBL coating inhibited the release of model drug of ibuprofen. Synchrotron radiation-based Fourier-transform infrared spectromicroscopy (SR-FTIR) has been applied to investigate the material distributions on the cross section of pellets and film. Characteristic absorptions of the compositions were obtained by SR-FTIR single spectrum scanning. The distributions of the drug and materials in coated films were determined by SR-FTIR mapping. The FTIR absorptions of chitosan and gelatin on the surface of lipid pellets was examined to verify the existence of chitosan and gelatin on the surface and a film formed using SR-FTIR ratio analysis. Whilst pellets coated only by chitosan or gelatin did not show the typical absorption of chitosan or gelatin, which confirmed the effects of ionic interaction on the film forming process. In conclusion, the method of SR-FTIR established for the study of the existence and distribution of materials in coated film offers a new choice for researches on membranes/films in drug delivery systems and pharmaceutical preparations.

10.
Chinese Journal of Analytical Chemistry ; (12): 1372-1377, 2016.
Artigo em Chinês | WPRIM | ID: wpr-503546

RESUMO

To investigate the mechanism of lead biosorption and biotransformation in lead-resistant bacteria in microcosmic scale, synchrotron radiation micro X-ray fluorescence (μ-SRXRF ) and X-ray absorption near edge structure ( XANES) was used to determine the element distribution characteristics and speciation of lead ( Pb) in lead-resistant bacteria strain isolated from farmland soil samples taken from a lead-zinc mine in Lanping county, Yunnan province in China. The isolated species was identified to be Arthrobacter sp. The concentration of Pb biosorpted in lead-resistant bacteria was directly determined byμ-SRXRF, and the results showed that the highest concentration was 5925μg/g and the bioaccumulate factor was 14 . 8 . Speciation of Pb in lead-resistant bacteria B2, LB ( Lysogeny Broth) medium and soil were also presented after using Pb LⅢXANES. Compared with Pb LⅢ XANES peak shape and peak position between standard samples, it was demonstrated that the Pb in lead-resistant bacteria was mainly formed by amorphous forms like PbS (58. 0%), (C17H35COO)2Pb (22. 2%), Pb5(PO4)3Cl (19. 8%) rather than organic Pb speciation which was exist in LB medium. Therefore, the isolated lead-resistant bacteria could biotransform Pb to sulfuric compounds. The biotransformation regular could be of great interest for other investigators as reference in study of bioavailability impact factor of heavy metals.

11.
Chinese Journal of Analytical Chemistry ; (12): 1447-1452, 2014.
Artigo em Chinês | WPRIM | ID: wpr-454013

RESUMO

Synchrotron radiation X-ray fluorescence analysis technology (SRXRF) can effectively reduce the detection limit for the determination of heavy metal elements, especially suitable for in situ nondestructive analysis of biological samples with low contents. By corn seed germination test, and combining with SRXRF technology, the effects of Pb on corn seed germination and Pb micro-distribution in the corn seed were studied. X-ray absorption near edge structure (XANES ) technique was used to analyze the Pb chemical speciation in different parts of corn seed. The above experiment was taken to understand the absorption and transformation mechanism of Pb by corn seeds. Results showed that germination rate, bud length and root length decreased with increased Pb contents. The analysis of variance showed that P-value of the germination rate, bud length and root elongation of corn seeds which were exposed to different concentration of Pb were 2. 0×10-3, 1. 4×10-4 and 2. 39×10-8, which were all less than 0. 01, therefore there were highly significant differences during these three indicators and the content of Pb. In addition, the inhibition effect on root growth was greater. SRXRF analysis results showed that Pb was mainly enriched in episperm and embryo, which would inhibit embryonic develop into bud and root. The Pb-LⅢ(13035 eV) XANES spectra of all samples include of root, shoot and the different part of seed were the same, they were the same speciation. Linear combination fitting results indicated that the lead phosphate chloride and lead stearate accounted for 74 . 3 %and 24. 2 % respectively, which suggested that the main Pb speciation of corn was lead phosphate chloride which deposited inside of corn, and a few combined with carboxylic to form the organic lead.

12.
Korean Journal of Medical Physics ; : 117-123, 2011.
Artigo em Inglês | WPRIM | ID: wpr-99722

RESUMO

Synchrotron radiation (SR) imaging enables us to observe internal structures of biologic samples without staining. In this study, we obtained X-ray microscopic images of human breast tissues with 11.1 KeV hard X-ray microscope of the Pohang light source and used zone plates and phase-contrast technique to get high resolution X-ray images. Hard X-ray microscopic images of fibrocystic change and breast cancer tissues with a spatial resolution of 60 nm were obtained and from these images, we could observe the micro-structures of human breast tissue. Also we analyzed and compared these images, which revealed distinct features of each condition. In conclusion, SR imaging with phase-contrast hard X-ray microscope for medical application, especially in breast disease can give some useful information for clinical research.


Assuntos
Humanos , Mama , Doenças Mamárias , Neoplasias da Mama , Luz , Síncrotrons
13.
Journal of Breast Cancer ; : 349-356, 2010.
Artigo em Inglês | WPRIM | ID: wpr-187770

RESUMO

PURPOSE: A significant improvement of imaging using synchrotron radiation (SR) is obtained by introducing phase-contrast technique. This technique provides greatly enhanced contrast and good soft tissue discrimination with high spatial resolution. The aim of this study was to observe microstructures of pathologic breast specimens including invasive breast cancer using phase-contrast technique with SR and to evaluate the feasibility of phase-contrast imaging in clinical application. METHODS: Phase-contrast microscopic image of normal breast tissue and the images of various breast diseases such as fibrocystic change, ductal carcinoma in situ, invasive ductal carcinoma, Paget's disease were obtained using hard X-ray microscopy with an 11.1 keV monochromatic beam from SR source and CsI (TI) scintillation crystal. Zernike phase-shifter was adapted for phase-contrast hard X-ray microscopy. The visual image was magnified 20 times by microscopic objective lens and captured using a full frame charge-coupled device camera. Obtained images were compared with corresponding histopathologic findings in the optical microscopy. RESULTS: The SR images of various breast diseases were obtained with a good contrast and high visibility by phase-contrast technique. It was possible to observe the microstructures with high spatial resolution down to the micron region. The characteristic features of each disease were consistent with the histopathologic findings of corresponding sample and the images of breast cancer and the other diseases were distinct from each other. CONCLUSION: Using phase-contrast technique, SR images of various breast diseases including breast cancer were obtained. These images were comparable with standard histopathologic findings and showed different features for each disease. The results suggest that phase-contrast microscopic imaging with SR has potential as a diagnostic tool and also its clinical application is feasible, especially in breast imaging.


Assuntos
Mama , Doenças Mamárias , Neoplasias da Mama , Carcinoma Ductal , Carcinoma Intraductal não Infiltrante , Discriminação Psicológica , Microscopia , Microscopia de Contraste de Fase , Síncrotrons
14.
Journal of Breast Cancer ; : 40-44, 2008.
Artigo em Coreano | WPRIM | ID: wpr-43959

RESUMO

PURPOSE: X-ray microscopy with synchrotron radiation might be a useful tool for novel x-ray imaging in the clinical and laboratory settings. This technique provides detailed images of internal structures non-invasively. It also has the potential to resolve some of the limitations of conventional breast imaging. We evaluated high resolution synchrotron imaging of breast tissues from normal breasts and breasts with fibroadenomas and cancer. METHODS: A new x-ray microscope was installed on the 1B2 beamline of a Pohang Light Source, at a third generation synchrotron radiation facility in Pohang, Korea. The phase contrast x-ray energy was set at 6.95 keV and the x-ray beam was monochromatized by a W/B4C monochromator. Formalinfixed or unfixed female breast tissue from normal breast as well as breasts with fibroadenomas and carcinoma were attached onto the Kapton film. The sample was positioned 25 m away from the beam source. The x-ray image of the sample was converted into a visual image on the CsI (TI) scintillation crystal, and magnified 20 times by the microscopic objective lens. After an additional 10 fold digital magnification, this visual image was captured by a full frame CCD camera. RESULTS: The monochromated x-ray microscopic images of female breast tissue from normal breast, fibroadenoma and carcinoma cases were evaluated. The total magnifying power of the microscope was x200. This synchrotron radiation imaging enabled us to observe detailed structures of breast tissue without sample preparation such as staining or fixation. CONCLUSION: Using monochromated synchrotron radiation, the x-ray microscopic images of the normal breast and breasts with fibroadenomas and cancer were obtained. From the images obtained, the x-ray microscopic imaging of breast tissue with synchrotron radiation appears to have great potential for clinical and research purposes such as oncology studies, early detection of cancer and as an aid to the pathological diagnosis in the future.


Assuntos
Feminino , Humanos , Mama , Detecção Precoce de Câncer , Fibroadenoma , Coreia (Geográfico) , Luz , Microscopia , Síncrotrons
15.
Yonsei Medical Journal ; : 95-103, 2005.
Artigo em Inglês | WPRIM | ID: wpr-35927

RESUMO

A simple imaging setup based on the principle of coherence-based contrast X-ray imaging with unmonochromatized synchrotron radiation was used for studying mammographic phantom and human breast specimens. The use of unmonochromatized synchrotron radiation simplifies the instrumentation, decreases the cost and makes the procedure simpler and potentially more suitable for clinical applications. The imaging systems consisted of changeable silicon wafer attenuators, a tungsten slit system, a CdWO4 scintillator screen, a CCD (Charge Coupled Device) camera coupled to optical magnification lenses, and a personal computer. In preliminary studies, a spatial resolution test pattern and glass capillary filled with air bubbles were imaged to evaluate the resOolution characteristics and coherence-based contrast enhancement. Both the spatial resolution and image quality of the proposed system were compared with those of a conventional mammography system in order to establish the characteristic advantages of this approach. The images obtained with the proposed system showed a resolution of at least 25micrometer on the test pattern with much better contrast, while the images of the capillary filled with air bubbles revealed coherence-based edge enhancement. This result shows that the coherence-based contrast imaging system, which emphasizes the refraction effect from the edge of materials of different refractive indexes, is applicable to imaging studies in fundamental medicine and biology, although further research works will be required before it can be used for clinical applications.


Assuntos
Feminino , Humanos , Doenças Mamárias/diagnóstico por imagem , Estudo Comparativo , Mamografia/instrumentação , Imagens de Fantasmas , Projetos Piloto , Síncrotrons , Raios X
16.
Yonsei Medical Journal ; : 25-30, 2002.
Artigo em Inglês | WPRIM | ID: wpr-71383

RESUMO

Ionizing radiation has long been used in medicine since the discovery of X-rays. Diagnostic imaging using synchrotron radiation has been under investigation since Rubenstein et al. reported dual-energy iodine-K-edge subtraction coronary angiography. Recently, computed tomography (CT) and magnetic resonance imaging (MRI) have provided better quality results than conventional radiology, providing important information on human internal structures. However, such techniques are unable to detect fine micron sized structures for the early diagnosis of tumors, vascular diseases and other medical objectives. Third generation synchrotron X-rays are well known for their superiority in coherence and energy tunability with respect to conventional X-rays. Consequently, new contrast mechanisms with a superior spatial resolution are becoming available. Here we present the extremely fine details of live animal internal structures using unmonochromatized synchrotron X-rays (white beam) and a simple detector system. Natural movements of the internal organs are also shown. The results indicate that this imaging technique can be applied to investigating microstructures and evaluating the function of the internal organs. Furthermore, this imaging system may be applied to humans as the next tool beyond CT and MRI.


Assuntos
Masculino , Camundongos , Animais , Diagnóstico por Imagem , Camundongos Pelados , Síncrotrons
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