Effectiveness of resveratrol as a hepatoprotector in a rat model of paracetamol-induced liver injury / Eficácia do resveratrol como hepatoprotetor em modelo de rato com lesão hepática induzida por paracetamol

Objective: Evaluate the effectiveness of resveratrol as a hepatoprotector in a rat model of paracetamol-induced liver injury and its biodistribution to understand its pharmacokinetics. Methodology: As an experimental approach, animals were divided into the test group with 4 subgroups and the control group with 4 subgroups. Animals of the "treated" group were subjected to resveratrol pre-treatment for eight days, followed by intoxication with a high dose of paracetamol on the 8th day. Animals were euthanized to collect the blood and liver tissue samples 24 and 72 h after the last administration. Hepatoprotective activity was evaluated through serum levels of glycogen and hepatic enzymes, such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP), histological and morphometric analysis of the liver tissue. For biodistribution analysis, different organs (organs, kidneys, heart and lungs) were collected and macerated, and resveratrol was quantified using high-performance liquid chromatography. Statistical analyses of morphometry, transaminases and alkaline phosphatase measurements, and biodistribution results were performed using GraphPad Prism® 3.0. Differences between groups were compared using ANOVA, followed by the Bonferroni test. Statistical significance was set at p < 0.05. Results: Resveratrol has a hepatoprotective action against acute intoxication by paracetamol, as evidenced by the histological decrease in necrosis and inflammatory foci, preservation of glycogen and other 1,2-glycols in zone 3, and reduction of serum ALT and AST levels. An increased presence of collagen was observed in acinar zones 1 and 3 with picrosirius red staining; therefore, quantification was performed in these regions showing smaller collagen areas in the R and RP groups than in the PC and NC groups Paracetamol caused a significant reduction in the resveratrol concentration in serum and the organs studied, indicating that the antioxidant activity of resveratrol is related to its hepatoprotective action. Conclusion: Resveratrol has hepatoprotective properties and can mitigate some of the liver damage caused by high doses of paracetamol, as indicated by changes in tissue characteristics and liver enzyme levels.

Objetivo: Avaliar a eficácia do resveratrol como hepatoprotetor em modelo de rato com lesão hepática induzida por paracetamol e sua biodistribuição para compreender sua farmacocinética. Metodologia: Como abordagem experimental, os animais foram divididos em grupo teste com 4 subgrupos e grupo controle com 4 subgrupos. Os animais do grupo "tratado" foram submetidos ao pré-tratamento com resveratrol durante oito dias, seguido de intoxicação com alta dose de paracetamol no oitavo dia. Os animais foram eutanasiados para coleta de amostras de sangue e tecido hepático 24 e 72 horas após a última administração. A atividade hepatoprotetora foi avaliada através dos níveis séricos de glicogênio e de enzimas hepáticas, como aspartato aminotransferase (AST), alanina aminotransferase (ALT) e fosfatase alcalina (ALP), análise histológica e morfométrica do tecido hepático. Para análise de biodistribuição, diferentes órgãos (órgãos, rins, coração e pulmões) foram coletados e macerados, e o resveratrol foi quantificado por cromatografia líquida de alta eficiência. Análises estatísticas de morfometria, medidas de transaminases e fosfatase alcalina e resultados de biodistribuição foram realizadas utilizando GraphPad Prism® 3.0. As diferenças entre os grupos foram comparadas por meio de ANOVA, seguida do teste de Bonferroni. A significância estatística foi estabelecida em p < 0,05. Resultados: O resveratrol tem ação hepatoprotetora contra a intoxicação aguda por paracetamol, evidenciada pela diminuição histológica da necrose e dos focos inflamatórios, preservação do glicogênio e outros 1,2-glicóis na zona 3 e redução dos níveis séricos de ALT e AST. Foi observada presença aumentada de colágeno nas zonas acinares 1 e 3 com coloração picrosirius red; portanto, foi realizada quantificação nessas regiões mostrando menores áreas de colágeno nos grupos tratados com resveratrol e resveratrol associado com paracetamol do que nos grupos controles positivo e negativo. O paracetamol causou redução significativa na concentração de resveratrol no soro e nos órgãos estudados, indicando que a atividade antioxidante do resveratrol está relacionada à sua ação hepatoprotetora. Conclusão: O resveratrol possui propriedades hepatoprotetoras e pode mitigar alguns dos danos hepáticos causados por altas doses de paracetamol, conforme indicado por alterações nas características dos tecidos e nos níveis de enzimas hepáticas.

Preparation and Biodistribution of 131I-labeled Hepatoma Nucleic Acid Nanotrain / 中山大学学报(医学科学版)

ObjectiveTo construct 131Ⅰ-labeled hepatoma nucleic acid nanotrain and to explore its feasibility as a new nuclide carrier targeting hepatoma. MethodsThree short nucleic acid chains self-assembled to a long nucleic acid chain after being annealed， and 131Ⅰ-NT was obtained by radioiodine labeling using chloramine T method. The labeling efficiency and radiochemical purity of the nanoparticles were measured by paper chromatography. The stability of the labeled products in vitro at different temperatures and different storage solvents was detected. The specific uptake of nanoparticles by hepatocellular carcinoma cells was observed by laser confocal microscopy， and the radioactive uptake ratio of 131Ⅰ-NT combined with human hepatocellular carcinoma cell HepG2 and normal hepatocyte L02 was measured. The biodistribution of 131Ⅰ-NT was obtained through injecting 131Ⅰ-NT into HepG2 tumor-bearing mice via tail vein. ResultsThe labeling rate of 131Ⅰ-NT was （93.05±0.74） %， and the radiochemical purity post purification was （98.35±0.32） %. Its radiochemical purity in PBS and pure serum at 4℃ for 24 h was （92.77±0.04） % and （89.43±0.2） %， respectively. The radioactivity uptake rate of HepG2 cells was higher than that of L02 cells after 131Ⅰ-NT was incubated with two kinds of cells for 2 h significantly. After injection of 131Ⅰ-NT through tail vein， the radioactive uptake per gram of tumor tissue were （4.9±0.55）%ID/g， （10.12±0.32）%ID/g and （4.25±0.31）%ID/g at 30 min， 1 h and 2 h， respectively. The T/M ratio was 7.33±2.04， 36.54±12.72 and 44.93±7.90 respectively. ConclusionsThe 131Ⅰ-labeled long chain nucleic acid nanotrain was constructed successfully， which possesses relatively high stability in vitro ， and high targeting ability to HepG2 cells in vitro and HepG2 tumor-bearing mouse model. Our study demonstrated that 131Ⅰ-NT may be a potential radionuclide carrier targeting human liver cancer， which provides a new idea for the targeted radionuclide diagnosis and treatment of hepatocellular carcinoma.

Pharmacokinetic analysis of mouse short interspersed nuclear element B1 antisense RNA / 中国生物制品学杂志

@#Objective To investigate the biological distribution of B1 antisense RNA(Blas RNA) of mouse short interspersed nuclear element in blood and tissues of normal mice after vein injection and detect the cell uptake efficiency of B1 as RNA using cultured normal mouse embryo cells after transfection.Methods Six 8～12-week-old BALB/c mice,three males and three females,were injected with 20 μg Blas RNA via tail vein,and blood samples were collected at different times after injection.54 BALB/c mice of 8～12-weeks were injected with 20 μg Blas RNA via tail vein,of which six mice,three males and three females,were euthanized at different times after injection,and various tissues,including the heart,liver,spleen,lung,kidney and thymus were harvested.Blas RNA was transfected into cultured mouse embryonic cells,and a certain amount of cells were taken at different time after transfection.The biological distribution of B1as RNA in mouse blood and different tissues and the persistence of Blas RNA in cultured embryo cells were detected by RT-qPCR.30naturally senescent BALB/c mice(≥ 14 months old) were divided into three groups:treatment group(20 μg Blas RNA injected via tail vein,once a week),irrelevant RNA control group(20 μg LacZ3F3R RNA injected via tail vein,once a week) and saline control group(injected with the same volume of saline),with 10 mice in each group,and a young control group(normal young 8～12-week-old BALB/c mice,five males and five females) was set.Four weeks after administration,mice in each group were euthanized,the liver tissues were taken,and the expression levels of aging-related genes(Sirtl,p21,p16~(Ink4a),p15~(Ink4b),p19~(Arf)) were detected by RT-qPCR.Results After tail vein injection,Blas RNA was available in the blood of mice for approximately 30 min,persisted for approximately 2～4 h in most detected tissues and persisted for approximately 48 h in lungs.The efficiency of cellular uptake of Blas RNA was approximately 400 molecules per mouse embryo culture cell 45 min after transfection with B1as RNA.Compared with the saline control group,Blas RNA treatment significantly down-regulated the mRN A expression of p21,p16~(In4a),p15~(In4b) and p19~(Arf) genes(t=10.01,4.461,4.420 and 5.309 respectively,each P <0.05),and significantly up-regulated the mRNA expression of Sirt1 gene(t=4.579,P <0.05).Conclusion Blas RNA was efficiently taken up by cells after transfection.After intravenous injection,Blas RNA stayed in the blood and tissues for a certain period of time and regulated the expression of aging-related genes in aged mice so as to make them approach to the expression level of young normal mice.

99m Technetium-HMPAO-labeled platelet scan in practice: Preparation, quality control, and biodistribution studies

Abstract There is no biodistribution or imaging data on 99mtechnetium (Tc)-hexamethyl propylamine oxime (HMPAO)-labeled platelets in the literature. The current study aimed to present updated information about the clinical procedures for preparation and use of labeled platelets. Following two-step centrifugation at 1500 and 2500 rpm, the platelets were extracted from whole blood into platelet-rich plasma (PRP) above the buffy coat and then from PRP into a platelet pellet at the bottom of the tube. The 99mTc-HMPAO-labeled platelets were inspected for purity, viability, release of 99mTc from platelets, and sterility. Also, microscopic examination and thin layer chromatography (TLC) were performed. Biodistribution was assessed following necropsy in BALB/c mice and through imaging of New Zealand rabbits. The separation ratio was estimated at 98%, and radiochemical purity was measured to be 80%. The labeling efficiency was above 30% in more than half of the assays (range: 17-43%). The release of 99mTc from platelets was 9% per hour at 37ºC. After 24 hours, stability was estimated at 54% in the human serum. The target organs of mice included the spleen and liver. In rabbits, the imaging results indicated liver as the target organ. Thyroid uptake was negligible up to 90 minutes. Based on the findings, extraction of platelets and labeling them with 99mTc-HMPAO is a feasible and safe approach in routine practice.

Glyceryl behenate-based solid lipid nanoparticles as a carrier of haloperidol for nose to brain delivery: formulation development, in-vitro, and in-vivo evaluation

Abstract This study was aimed to develop the haloperidol (HPL) loaded solid lipid nanoparticles (SLNs) for brain targeting through the intranasal route. SLNs were fabricated by the emulsification diffusion technique using glyceryl behenate as lipid and tween 80 as a surfactant. SLNs were evaluated for particle size, zeta potential, structure, entrapment efficiency, solid state characterization by differential scanning calorimetry (DSC), and in-vitro release. In-vivo biological evaluation was performed on albino Wistar rats for the determination of pharmacokinetic as well as brain targeting parameters. Particle size, PDI, zeta potential, and entrapment efficiency of optimized formulation (HPL-SLNs 6) were found to be 103±09 nm, 0.190±0.029, -23.5±1.07 mV, and 79.46±1.97% respectively. In-vitro drug release studies exhibited that 87.21± 3.63% of the entrapped drug was released from the SLNs within 24 h. DSC curves confirmed that during entrapment in SLNs, the drug was solubilized in the lipid matrix and converted into the amorphous form. Enhanced HPL targeting to the brain was observed from HPL-SLNs as compared to HPL-Sol when administered intranasally. The value of AUC 0-∞ in the brain for HPL-SLNs i.n. was found to be nearly 2.7 times higher than that of HPL-Sol i.v., whereas 3.66 times superior to HPL-Sol administered i.n. Stability studies revealed that the formulation remains unchanged when stored at 4±2 °C (refrigerator) and 25±2 °C /60 ±5% RH up to six months. Finally, it could be concluded that SLN is a suitable carrier for HPL with enhanced brain targeting through i.n administration, as compared to the HPL-Sol, administered i.n. and i.v.

Development of fluorescent- and radio-traceable T1307-polymeric micelles as biomedical agents for cancer diagnosis: biodistribution on 4T1 tumor-bearing mice

Abstract In recent years, nanocarriers have been studied as promising pharmaceutical tools for controlled drug-delivery, treatment-efficacy follow-up and disease imaging. Among them, X-shaped amphiphilic polymeric micelles (Tetronic®, poloxamines) display great potential due to their biocompatibility and non-toxic effects, among others. In the present work, polymeric micelles based on the T1307 copolymer were initially decorated with a 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY)-fluorophore in order to determinate its in vivo biodistribution on 4T1 tumor-bearing mice. However, unfavorable results with this probe led to two different strategies. On the one hand, the BODIPY-micelle-loaded, L-T1307-BODIPY, and on the other hand, the 99mTc-micelle-radiolabeled, L-T1307- 99m Tc, were analyzed separately in vivo. The results indicated that T1307 accumulates mainly in the stomach, the kidneys, the lungs and the tumor, reaching the maximum organ-accumulation 2 hours after intravenous injection. Additionally, and according to the results obtained for L-T1307- 99m Tc, the capture of the polymeric micelles in organs could be observed up to 24 hours after injection. The results obtained in this work were promising towards the development of new radiotracer agents for breast cancer based on X-shaped polymeric micelles.

Radiation dosimetry and biodistribution of 68Ga-FAPI-04 PET in patients with hepatobiliary tumor / 中华放射医学与防护杂志

Objective:To investigate the radiation dosimetry and biodistribution of 68Ga-FAPI-04 PET/CT in patients with hepatobiliary tumor. Methods:A total of six patients with hepatic lesions who underwent PET/CT examination in Peking Union Medical College Hospital were enrolled. After intravenous injection of radiotracer 68Ga-FAPI-04 at (170.57 ± 14.43) MBq, whole-body imaging were performed at the time points of 3, 10, 15, 20, 30 and 60 min, respectively. Biodistribution pattern was observed. Regions of interest were manually delineated. Radiation dosimetry of all target organs were calculated by Olinda/EXM software. Results:The radioactive uptake dissipated gradually in liver whereas it was relatively stable in tumor lesions. The average SUV max of tumor lesions reached the maximum value (13.87± 2.55) at 20 min after injection. The target-to-background ratio increased with time, reaching the maximum value (10.09 ± 8.17) at 30 min after injection. The average effective dose in total body was (0.020 ± 0.002) mSv/MBq and organ with the highest effective dose was bladder wall at (0.146 ± 0.035) mSv/MBq. Conclusions:The effective dose in total body of 68Ga-FAPI-04 was similar to that of 18F-FDG. 68Ga-FAPI-04 is expected to be a PET/CT radiotracer for hepatobiliary tumors in consideration of rapid tumor uptake, low accumulation of liver background, and no influence of blood sugar levels.

Comparison of Gallium - 68 Prostate-Specific Membrane Antigen (Ga-68 PSMA) normal tissue uptake across tumor burden groups among Filipino patients with prostate cancer

Background@#PSMA-targeted radiopharmaceuticals have been widely studied for their theragnostic role in prostate cancer and were introduced in the Philippines in 2018. The optimal administered activity of 177Lu-PSMA for targeted endoradiotherapy has not yet been established and is thought to be influenced by several factors, including tumor burden. This study investigates the effect of tumor burden on the normal tissue PSMA uptake among Filipino patients with prostate cancer using its diagnostic counterpart, 68Ga-PSMA I&T @*Methods@#One hundred four patients imaged with 68Ga-PSMA I&T PET/CT in our institution from January 2018 to May 2020 were included. Patients were visually classified into low, medium, and high tumor burden groups. Maximum and mean standardized uptake values (SUVmax and SUVmean) of the lacrimal glands, parotid glands, submandibular glands, kidneys, liver, spleen, and bone were measured and compared among tumor burden groups. @*Results and Conclusions@#68Ga-PSMA I&T uptake in the kidneys, the salivary glands, and the liver, were significantly reduced by approximately 25-50% in patients with high tumor burden. This finding supports the hypothesis that patients with higher tumor load can tolerate higher activity doses of 177Lu-PSMA for endoradiotherapy before developing significant damage to the critical organs. This may serve as a guide towards optimizing and personalizing 177Lu-PSMA I&T administered activity dose for radionuclide therapy

The biological fate of the polymer nanocarrier material monomethoxy poly(ethylene glycol)-

Monomethoxy poly(ethylene glycol)-

The contribution of absorption of integral nanocrystals to enhancement of oral bioavailability of quercetin

In this study, self-discriminating hybrid nanocrystals was utilized to explore the biological fate of quercetin hybrid nanocrystals (QT-HNCs) with diameter around 280 nm (QT-HNCs-280) and 550 nm (QT-HNCs-550) following oral and intravenous administration and the contribution of integral nanocrystals to oral bioavailability enhancement of QT was estimated by comparing the absolute exposure of integral QT-HNCs and total QT in the liver. Results showed that QT-HNCs could reside

Radiolabeling of cidofovir with technetium-99m and biodistribution studies

Radiolabeling cidofovir with technetium-99m (99mTc-CDV) is an innovative procedure that enables real-time monitoring of the drug. Essays were performed in vitro, showing high radiolabel stability within 24 h. Blood clearance, biodistribution studies, and scintigraphic images were performed in healthy mice in order to evaluate the profile of the drug in vivo. 99mTc-CDV showed biphasic blood circulation time and significant kidney uptake, indicating that 99mTc-CDV is preferentially eliminated by the renal route. Bones also showed important uptake throughout the experiment. In summary, cidofovir was successfully labeled with technetium-99m and might be used in further studies to track the drug.

In vivo Imaging Biodistribution Profile of a New Macrocyclic Gadolinium Chelate as a Highly Stable Multifunctional MRI Contrast Agent

Gadolinium contrast agents (CAs) are integral components of clinical magnetic resonance imaging (MRI). However, safety concerns have arisen regarding the use of gadolinium CAs, due to their association with nephrogenic systemic fibrosis (NSF). Furthermore, recently the long-term retention of Gd²⁺-based CAs in brains patients with normal renal function raised another possible safety issue. The safety concerns of Gd²⁺-based CAs have been based on the ligand structure of Gd²⁺-based CAs, and findings that Gd²⁺-based CAs with linear ligand structures showed much higher incidences of NSF and brain retention of CAs than Gd²⁺-based CAs with macrocyclic ligand structure. In the current study, we report the in vivo biodistribution profile of a new highly stable multifunctional Gd²⁺-based CA, with macrocyclic ligand structure (HNP-2006). MR imaging using HNP-2006 demonstrated a significant contrast enhancement in many different organs. Furthermore, the contrast enhanced tumor imaging using HNP-2006 confirmed that this new macrocyclic CA can be used for detecting tumor in the central nervous system. Therefore, this new multifunctional HNP-2006 with macrocyclic ligand structure shows great promise for whole-body clinical application.

Solid dispersion-based pellet for colon delivery of tacrolimus through time- and pH-dependent layer coating: preparation, in vitro and in vivo studies

The intent of the present investigation is to develop and evaluate colon-specific coated tacrolimus solid dispersion pellet (SDP) that retards drug release in the stomach and small intestine but progressively releases in the colon. Tacrolimus-SDP was prepared by extrusion-spheronization technology and optimized by the micromeritic properties including flowability, friability, yields and dissolution rate. Subsequently, the pH-dependent layer (Eudragit L30D55) and time-dependent layer (Eudragit NE30D and L30D55) were coated on the SDP to form tacrolimus colon-specific pellets (CSP) using a fluidized bed coater. Under in vitro gradient pH environment, tacrolimus only released from CSP after changing pH to 6.8 and then quickly released in the phosphate buffer solution of pH 7.2. The Cmax of CSP was 195.68 ± 3.14 ng/mL at Tmax 4.5 ± 0.24 h where as in case of SDP, the Cmax was 646.16 ± 8.15 ng/mL at Tmax 0.5 ± 0.03 h, indicating the ability of CSP targeted to colon. The highest area under the curve was achieved 2479.58 ± 183.33 ng·h/mL for SDP, which was 2.27-fold higher than tacrolimus suspension. However, the best biodistribution performance was achieved from CSP. In conclusion, SDP combining of pH- and time-dependent approaches was suitable for targeted delivery of tacrolimus to colon.

Pharmacokinetics of neutron-irradiated meglumine antimoniate in Leishmania amazonensis-infected BALB/c mice

Cutaneous leishmaniasis (CL) is a parasitic disease caused by the protozoan Leishmania spp. Pentavalent antimonial agents have been used as an effective therapy, despite their side effects and resistant cases. Their pharmacokinetics remain largely unexplored. This study aimed to investigate the pharmacokinetic profile of meglumine antimoniate in a murine model of cutaneous leishmaniasis using a radiotracer approach. Methods: Meglumine antimoniate was neutron-irradiated inside a nuclear reactor and was administered once intraperitoneally to uninfected and L. amazonensis-infected BALB/c mice. Different organs and tissues were collected and the total antimony was measured. Results: Higher antimony levels were found in infected than uninfected footpad (0.29% IA vs. 0.14% IA, p = 0.0057) and maintained the concentration. The animals accumulated and retained antimony in the liver, which cleared slowly. The kidney and intestinal uptake data support the hypothesis that antimony has two elimination pathways, first through renal excretion, followed by biliary excretion. Both processes demonstrated a biphasic elimination profile classified as fast and slow. In the blood, antimony followed a biexponential open model. Infected mice showed a lower maximum concentration (6.2% IA/mL vs. 11.8% IA/mL, p = 0.0001), a 2.5-fold smaller area under the curve, a 2.7-fold reduction in the mean residence time, and a 2.5-fold higher clearance rate when compared to the uninfected mice. Conclusions: neutron-irradiated meglumine antimoniate concentrates in infected footpad, while the infection affects antimony pharmacokinetics.(AU)

Características de la imagen con 68Ga-PSMA PET/CT. Biodistribución normal y anormal / Image features with 68Ga-PSMA PET/CT. Normal and abnormal biodistribution

Un sistema de PET/CT integrado o multimodal es una combinación física de PET y CT que incluye adquisición secuencial de porciones de PET y CT. El paciente permanece en la misma posición durante los dos exámenes. Un examen 68Ga-PSMA PET/CT puede cubrir diversos rangos de imágenes coaxiales1. PSMA es una proteína transmembrana presente principalmente en todos los tejidos prostáticos. Este articulo tiene como objetivo ayudar a los médicos imagenólogos para clínicos, a reconocer las imágenes de 68Ga-PSMA PET/CT mostrar características propias y ofrecer conocimientos generales de su interpretación en el área de diagnósticos dirigido al cáncer de próstata.

Avaliação de protetores solares contendo filtros encapsulados/incorporados em matriz de sílica mesoporosa ordenada do tipo SBA-15 / Evaluation of sunscreens containing encapsulated/entrapped UV filters in ordered mesoporous silica type SBA-15

Filtros orgânicos são amplamente utilizados em formulações fotoprotetoras, com habilidade de absorver radiações ultravioleta (UV). Contudo, parte destes compostos possuem limitações, como: fotoinstabilidade, permeação cutânea e fotossensibilização e entre outros. Este trabalho envolveu a síntese de matriz mesoporosa do tipo SBA-15, encapsulação/incorporação de ρ-metoxicinamato de octila (MCO), benzofenona-3 (BZF-3) e avobenzona (AVO) na SBA-15 para aplicação em formulações fotoprotetoras. Fez-se a determinação da eficácia in vitro dos filtros encapsulados/incorporados combinados a ingrediente cosmético; o preparo de bastão fotoprotetor e determinação eficácia estimada; a avaliação do potencial de irritação ocular dos bastões por HET-CAM - Hen's Egg Test - Chorioallantoic Membrane, e a avaliação da permeação/retenção cutânea e perfil de biodistribuição dos filtros. Para a caracterização dos materiais foram empregadas técnicas físico-químicas e analíticas. As medidas de adsorção/dessorção de N2 mostrou que as amostras dos filtros solares encapsulados/incorporados apresentaram diminuição na área superficial e volume de poro (V), indicando que os filtros solares foram encapsulados/incorporados na superfície e nos poros da SBA-15. Os resultados de Espalhamento de raios X a baixo ângulo evidenciaram que os filtros solares não afetaram a estrutura hexagonal da SBA-15. Por TG/DTG e análise elementar foi possível determinar a quantidade de filtros solares na superfície e nos mesoporos da SBA-15. Enquanto, as curvas DSC e DTA revelaram aumento na estabilidade térmica da AVO e BZF-3, quando encapsulados/incorporados. Os resultados da eficácia fotoprotetora in vitro mostraram que a combinação dos três filtros solares encapsulados/incorporados na SBA-15 promoveram aumento de 52% no fator proteção solar (FPS), enquanto que, na formulação fotoprotetora contendo os três filtros encapsulados/incorporados, o aumento foi de 94%. O ensaio de HET-CAM evidenciou que os bastões contendo SBA-15 e os filtros encapsulados/incorporados não foram irritantes. O ensaio de permeação/retenção cutânea mostrou que o processo de encapsulação/incorporação da BZF-3 promoveu diminuição de sua permeação em todos os tempos de exposição. As quantidades permeadas de AVO e MCO ficaram abaixo do limite de quantificação nos tempos 6 e 12 h, no entanto, no tempo de 24 h foi possível quantificá-los. As quantidades dos filtros solares retidas na pele a partir da formulação contendo os filtros solares encapsulados/incorporados na SBA-15 (F4) foram menores (tempos 6 e 12 h) em comparação à formulação contendo os filtros solares não encapsulados (F3). A investigação da biodistribuição dos filtros solares mostrou que a retenção total na pele, como na derme, foi menor na formulação F4 em comparação à F3. O estudo comparativo entre pele suína e a pele humana mostrou que as quantidades de BZF-3 e AVO permeadas e retidas na pele suína foram superiores do que em relação à humana para ambas as formulações (F4 e FR). Pela técnica de biodistribuição, foi possível determinar que os filtros solares oriundos das formulações F3 e referência (FR) apresentaram maior retenção destes compostos na derme do que em outras camadas da pele. Contudo, observou-se que os filtros encapsulados apresentaram taxa reduzida de retenção na derme

Organic Filters are chemical compounds widely used in sunscreens formulations with the ability to absorb ultraviolet radiation (UV). Despite the effectiveness of these compounds in UV radiation protection, disadvantages related to their photo instability, potential skin permeation and photo sensibility pose significant challenges for improving these products. The aim of this work was to synthesize mesoporous matrix SBA-15, encapsulation/entrapping of octyl methoxycinnamate (OMC), benzophenone-3 (BZF-3) and avobenzone (AVO) into SBA-15 for application in photoprotective formulations. It was accessed in vitro photoprotection efficacy and in vitro photostability assay of encapsulated/entrapped UV filters combined with cosmetic ingredient and photoprotective stick formulations; evaluation of the ocular irritation potential of photoprotective stick formulations by in vitro method HET-CAM - Hen's Egg Test - Chorioallantoic Membrane; evaluation the skin permeation/deposition and biodistribution profile of photoprotective stick formulations. The decrease in the surface area and in mesoporous volume (V) observed in the nitrogen adsorption desorption isotherms of encapsulated/entrapped samples indicated that UV filters were efficiently encapsulated/entrapped into SBA-15. Additionally, SAXS results showed that UV filters did not affected the hexagonal structure of the mesoporous material and that these compounds filled the SBA-15 pores. TG/DTG and elemental analysis were efficient tools to confirm the presence and the quantity of UV filters into SBA-15. DTA and DSC curves of encapsulated/entrapped materials showed that the thermal stability of AVO and BZF-3 were increased. On the other hand, DSC curves of encapsulated/entrapped materials demonstrated that thermal stability of OMC was not increase. The in vitro photoprotective efficacy results demonstrated that the combination of the three sunscreens encapsulated/entrapped into SBA-15 increased 52.0% the SPF values, while the stick formulation containing the UV filters encapsulated/entrapped, the increase was 94.0%. Delivery experiments using porcine skin demonstrated that the encapsulation/entrapping process of UV filters resulted the decreased of BZF-3 permeation and deposition in skin (6 and 12 hours). The cutaneous biodistribution profile of UV filters showed that the deposition of these compounds from encapsulated/entrapped stick formulation (F4) was significantly lower than that from UV filters stick formulations (F3) in the total slices of the skin and dermis. The comparative study between porcine skin and human skin demonstrated that the amounts of BZF-3 and AVO permeated and deposited in porcine skin were higher than in human skin for both formulations (F4 and FR - reference formulation). By the biodistribution technique it was possible to determine that the UV filters from the formulations F3 and FR presented higher retention of these compounds in the dermis than in other layers of the skin. On the other hand, it was observed that the encapsulated UV filters presented low retention rate into dermis

¹²³I-Labeled oxLDL Is Widely Distributed Throughout the Whole Body in Mice / 대한핵의학회잡지

PURPOSE: Oxidized low-density lipoprotein (oxLDL) plays a key role in endothelial dysfunction, vascular inflammation, and atherogenesis. The aim of this study was to assess blood clearance and in vivo kinetics of radiolabeled oxLDL in mice.METHODS: We synthesized ¹²³I-oxLDL by the iodine monochloride method, and performed an uptake study in CHO cells transfected with lectin-like oxLDL receptor-1 (LOX-1). In addition, we evaluated the consistency between the ¹²³I-oxLDL autoradiogram and the fluorescence image of DiI-oxLDL after intravenous injection for both spleen and liver. Whole-body dynamic planar images were acquired 10 min post injection of ¹²³I-oxLDL to generate regional time-activity curves (TACs) of the liver, heart, lungs, kidney, head, and abdomen. Regional radioactivity for those excised tissues as well as the bladder, stomach, gut, and thyroid were assessed using a gamma counter, yielding percent injected dose (%ID) and dose uptake ratio (DUR). The presence of ¹²³I-oxLDL in serum was assessed by radio-HPLC.RESULTS: The cellular uptakes of ¹²³I-oxLDL were identical to those of DiI-oxLDL, and autoradiograms and fluorescence images also exhibited consistent distributions. TACs after injection of ¹²³I-oxLDL demonstrated extremely fast kinetics. The radioactivity uptake at 10 min postinjection was highest in the liver (40.8 ± 2.4% ID). Notably, radioactivity uptake was equivalent throughout the rest of the body (39.4 ± 2.7% ID). HPLC analysis revealed no remaining ¹²³I-oxLDL or its metabolites in the blood.CONCLUSION: ¹²³I-OxLDL was widely distributed not only in the liver, but also throughout the whole body, providing insight into the pathophysiological effects of oxLDL.

Determination of biodistribution of 99mTc-3PRGD2 in mice bearing the lung carcinoma xenograft byγcounter / 国际药学研究杂志

Objective To establish a quantitative analysis method for determining 99mTc-HYNIC-PEG4-E[PEG4-c(RGDfK)]2 (99mTc-3PRGD2,a radioactive tumor agent)byγcounter, and to investigate the distribution of 99mTc-3PRGD2 in mice bearing with lung carcinoma xenograft. Methods The mice were divided into 4 normal groups and one blocking peptide group(control group). The 99mTc-3PRGD2(8μg/kg)was injected to mice bearing with lung carcinoma xenograft through the tail intravenous administration. Tissues of the normal mice were taken at 0.5,1,2 and 4 h. The control group were treated by 3PRGD2 and 99mTc-3PRGD2. The control mice were injected with the 3PRGD2 saline solution(2.5 mg/ml,0.2 ml)at 0.5 h earlier before the injection of 99mTc-3PRGD2. The tu?mor and organ tissues of the control mice were taken at 2 h. The radioactivity was detected by Gamma Counter. Results The radioac?tivity of 99mTc-3PRGD2 detected was high in the tumor and very low in brain. In addition,high radioactivity in kidneys and bladder sug?gested that the drug excreted by renal. Conclusion The results proved that the blocking peptide can competitively inhibit the combi?nation of 99mTc-3PRGD2 and integrinαvβ3 receptors.

Effect of Surface Charge on Biobehavior ofPEGylated Gold Nanoparticles / 分析化学

Three kinds of PEGylated gold nanoparticles (PEG-Au NPs) with different surface charges are prepared by assembly of thiolated polyethylene glycol (HS-PEG) with different terminal groups including methoxy, amino or carboxyl on gold nanoparticle surface through sulfur-gold covalent bond, respectively.The experimental results of cell co-culturing and tail intravenous injection in mouse indicate that the biological behaviors of PEG-Au NPs are affected significantly by their surface charges.The cellular internalization amounts of PEG-Au NPs are following the order, positive charge ＞ neutral charge ＞ negative charge.The PEG-Au NPs are gradually transferred to liver and spleen from main organs through the circulation of blood after tail intravenous injection in mouse.The negatively charged PEG-Au NPs have the slowest hepatic clearance rate while the positively charged PEG-Au NPs can cause the strongest response of immune system in mice.

Study on visualization of metabolic process of L-stepholidine in living rats by PET/CT in vivo / 中草药

Objective: To exolpre the feasibility to transform the metabolic process of active constituents of Chinese herbal medicine in vivo into images by PET/CT and to make quantitative analysis. Methods: The l-stepholidine was used as study object, and chemical synthesis of 11C-L-SPD was performed in hot room. PET/CT scan was performed in different time, 5, 15, 30, 45, 60, and 90 min after injecting 11C-L-SPD by vail in rats, and the information of brain, heart, lung, liver, kidney, intestine, and bladder was transferred to the Workststion. The distribution volume ratios (DVR) of the above tissues were obtained. Results: 11C-L-SPD was keeping in a relative higher level in liver and kidney at 5 min. metabolism through the liver, kidney was the main eccrisis organ. The distribution of 11C-L-SPD in liver, kidney, intestine, and bladder was (1.37 ± 0.42)%, (1.10 ± 0.19)%, (0.89 ± 0.18)%, and (0.97 ± 0.111)% respectively at 5 min and was (0.65 ± 0.11)%, (0.54 ± 0.05)%, (5.49 ± 1.44)%, and (9.86 ± 1.88)% respectively at 90 min. Conclusion: PET/CT imaging could observe the distribution and metabolism of 11C-L-SPD dynamically and directly. It could be used in the research of other Chinese medicines.