Advances in the application of microspheres and nanoparticles in transcatheter arterial chemoembolization for the treatment of hepatocellular carcinoma / 临床肝胆病杂志

In recent years， transcatheter arterial chemoembolization （TACE） has emerged as a common treatment modality for the treatment of hepatocellular carcinoma （HCC）. However， with the ongoing development of embolic agent techniques， the new advances in microspheres and nanoparticles have brought new hope for improving the efficacy and safety of TACE. This article reviews the latest advances and applications of microspheres and nanoparticles in TACE for HCC. First， this article introduces the background of TACE as a therapeutic approach and the emergence of microsphere and nanoparticle techniques， and then it describes the application of various types of microspheres and nanoparticles in TACE and discusses the requisite attributes of an ideal embolic agents. The article focuses on the advances in material science and engineering， as well as the clinical efficacy of drug-eluting microspheres and nanoparticles versus conventional TACE. Furthermore， it discusses the importance of radiological examination in TACE and summarizes the research advances in the radiopaque and magnetic resonance-visible embolic agents. This article also explores the future development directions and challenges of TACE. It also points out the combination of microspheres and nanoparticles with other treatment modalities， the application of personalized and precision medicine in TACE， and the potential regimen of TACE in clinical translation， and meanwhile， it raises the issues of ethics and regulation that need to be further discussed. It is believed that microspheres and nanoparticles have a potential effect in TACE， which provides a theoretical basis and technical support for innovating HCC treatment regimens and improving the prognosis of patients through TACE interventions.

Application of gelatin microspheres in bone tissue engineering / 生物工程学报

Gelatin microspheres were discussed as a scaffold material for bone tissue engineering, with the advantages of its porosity, biodegradability, biocompatibility, and biosafety highlighted. This review discusses how bone regeneration is aided by the three fundamental components of bone tissue engineering-seed cells, bioactive substances, and scaffold materials-and how gelatin microspheres can be employed for in vitro seed cell cultivation to ensure efficient expansion. This review also points out that gelatin microspheres are advantageous as drug delivery systems because of their multifunctional nature, which slows drug release and improves overall effectiveness. Although gelatin microspheres are useful for bone tissue creation, the scaffolds that take into account their porous structure and mechanical characteristics might be difficult to be created. This review then discusses typical techniques for creating gelatin microspheres, their recent application in bone tissue engineering, as well as possible future research directions.

Establishment of determination of tetrodotoxin sustained-release microspheres / 药学实践杂志

Objective To establish a detection method for the determination of tetrodotoxin (TTX) in sustained-release microspheres. Methods The HPLC separation of tetrodotoxin was performed on an Agilent ZORBAX SB-C18 column (4.6mm×150mm,5 μm) with acetonitrile, 8mmol/L sodium heptane sulfonate containing 0.005% TFA (5:95) (pH 4.0) as the mobile phase. The flow rate was 1.0 ml/min. The UV detection wavelength was 200 nm and the column temperature was 30 °C. Results The method had good specificity and linearity of TTX in the concentration range of 1−20 μg/ml. The intra-day precision, inter-day precision, stability and repeatability of the method were good, and the average recoveries were found between 98.0% and 102.0%. Conclusion This study established an HPLC method which was suitable for the determination of tetrodotoxin sustained-release microspheres. The method is accurate and reliable within the applicable range, with strong specificity, which could lead to quantitative detection.

Cell-loaded hydrogel microspheres based on droplet microfluidics: a review / 生物工程学报

Droplet microfluidics technology offers refined control over the flows of multiple fluids in micro/nano-scale, enabling fabrication of micro/nano-droplets with precisely adjustable structures and compositions in a high-throughput manner. With the combination of proper hydrogel materials and preparation methods, single or multiple cells can be efficiently encapsulated into hydrogels to produce cell-loaded hydrogel microspheres. The cell-loaded hydrogel microspheres can provide a three-dimensional, relatively independent and controllable microenvironment for cell proliferation and differentiation, which is of great value for three-dimensional cell culture, tissue engineering and regenerative medicine, stem cell research, single cell study and many other biological science fields. In this review, the preparation methods of cell-loaded hydrogel microspheres based on droplet microfluidics and its applications in biomedical field are summarized and future prospects are proposed.

Preparation and properties of silica/hydroxyapatite whiskers porous ceramics scaffold / 中国修复重建外科杂志

OBJECTIVE@#To investigate the preparation and properties of the novel silica (SiO 2)/hydroxyapatite (HAP) whiskers porous ceramics scaffold.@*METHODS@#The HAP whiskers were modified by the SiO 2 microspheres using the Stöber method. Three types of SiO 2/HAP whiskers were fabricated under different factors (for the No.1 samples, the content of tetraethoxysilane, stirring time, calcination temperature, and soaking time were 10 mL, 12 hours, 560℃, and 0.5 hours, respectively; and in the No.2 samples, those were 15 mL, 24 hours, 650℃, and 2 hours, respectively; while those in the No.3 samples were 20 mL, 48 hours, 750℃, and 4 hours, respectively). The phase and morphology of the self-made HAP whisker and 3 types of SiO 2/HAP whiskers were detected by the X-ray diffraction analysis and scanning electron microscopy. Taken the self-made HAP whisker and 3 types of SiO 2/HAP whiskers as raw materials, various porous ceramic materials were prepared using the mechanical foaming method combined with extrusion molding method, and the low-temperature heat treatment. The pore structure of porous ceramics was observed by scanning electron microscopy. Its porosity and pore size distribution were measured. And further the axial compressive strength was measured, and the biodegradability was detected by simulated body fluid. Cell counting kit 8 method was used to conduct cytotoxicity experiments on the extract of porous ceramics.@*RESULTS@#The SiO 2 microspheres modified HAP whiskers and its porous ceramic materials were prepared successfully, respectively. In the SiO 2/HAP whiskers, the amorphous SiO 2 microspheres with a diameter of 200 nm, uniform distribution and good adhesion were attached to the surface of the whiskers, and the number of microspheres was controllable. The apparent porosity of the porous ceramic scaffold was about 78%, and its pore structure was composed of neatly arranged longitudinal through-holes and a large number of micro/nano through-holes. Compared with HAP whisker porous ceramic, the axial compressive strength of the SiO 2/HAP whisker porous ceramics could reach 1.0 MPa, which increased the strength by nearly 4 times. Among them, the axial compressive strength of the No.2 SiO 2/HAP whisker porous ceramic was the highest. The SiO 2 microspheres attached to the surface of the whiskers could provide sites for the deposition of apatite. With the content of SiO 2 microspheres increased, the deposition rate of apatite accelerated. The cytotoxicity level of the prepared porous ceramics ranged from 0 to 1, without cytotoxicity.@*CONCLUSION@#SiO 2/HAP whisker porous ceramics have good biological activity, high porosity, three-dimensional complex pore structure, good axial compressive strength, and no cytotoxicity, which make it a promising scaffold material for bone tissue engineering.

Uterine artery embolization with highly compressible calibrated microspheres for the treatment of uterine fibroids / Embolização de miomas uterinos com microesferas calibradas de alta compressibilidade

Abstract Objective: To evaluate the safety and efficacy of using highly compressible calibrated microspheres in uterine artery embolization (UAE) for the treatment of uterine fibroids. Materials and Methods: This was a prospective multicenter study. Thirty-two women with symptomatic uterine fibroids were selected for UAE between January 2019 and March 2020. The participants completed the Uterine Fibroid Symptom and Quality of Life (UFS-QOL) questionnaire, underwent contrast-enhanced pelvic magnetic resonance imaging (MRI), and were submitted to anti-Müllerian hormone measurement, subsequently undergoing UAE with Embosoft microspheres. After six months, the patients again completed the UFS-QOL questionnaire and underwent pelvic MRI. Results: The most common symptoms were abnormal uterine bleeding (in 81.3% of the cases), pelvic pain (in 81.3%), and compression (in 46.9%). Of the 32 patients evaluated, 12 (37.5%) had anemia due to abnormal uterine bleeding. Thirty patients completed the study. Among those patients, we observed median reductions of 21.4% in uterine volume and 15.9% in dominant fibroid volume. We identified no adverse events that could be attributed to the material itself, although there were events attributed to the UAE procedure in general. Conclusion: For the treatment of uterine fibroids, UAE using Embosoft microspheres shows satisfactory results, providing reductions in uterine and dominant fibroid volumes, with a low rate of adverse events, and improving patient quality of life, as well as demonstrating safety and efficacy.

Resumo Objetivo: Avaliar a eficácia e segurança da embolização da artéria uterina (EAU) com microesferas calibradas de alta compressibilidade no tratamento de miomas uterinos. Materiais e Métodos: Este foi um estudo prospectivo e multicêntrico. Foram selecionadas 32 mulheres com miomas uterinos sintomáticos para EAU de janeiro de 2019 a março de 2020. As participantes preencheram o questionário Uterine Fibroid Symptom and Quality of Life (UFS-QOL), realizaram ressonância magnética (RM) pélvica com contraste e teste para medição dos hormônios antimüllerianos, seguido de embolização de miomas com microesferas Embosoft. Após seis meses, as pacientes novamente preencheram o UFS-QOL e realizaram RM pélvica. Resultados: Os sintomas mais relatados foram sangramento uterino anormal (81,3%), dor pélvica (81,3%) e compressão (46,9%). Doze pacientes (37,5%) apresentaram anemia consequente a sangramento uterino anormal. Nas 30 pacientes que completaram o estudo, observou-se redução mediana de 21,4% no volume uterino e 15,9% no volume do mioma dominante. Não foram identificados eventos adversos possivelmente relacionados ao material utilizado, apenas em relação ao procedimento de EAU. Conclusão: EAU com microesferas Embrosoft mostrou resultados satisfatórios no tratamento de miomas uterinos, com redução dos volumes uterino e do mioma dominante, baixa taxa de eventos adversos e melhora na qualidade de vida, demonstrando segurança e eficácia.

Preparation and physicochemical properties of PVA/HA composite microspheres for embolization / 国际生物医学工程杂志

Objective:To prepare polyvinyl alcohol (PVA) and hydroxyapatite (HA) composite embolization microspheres and investigate their physicochemical properties.Methods:PVA/HA composite embolization microspheres were prepared by reverse suspension polymerization, using PVA and HA as dispersed phases, liquid paraffin containing sorbitan fatty acid ester as the continuous phase, and glutaraldehyde as the cross-linking agent. The morphology, particle size distribution, and microscopic morphology of PVA/HA composite embolization microspheres were observed by optical microscopy and scanning electron microscopy. The chemical structure of PVA/HA composite embolization microspheres and the elasticity, drug loading, and drug release properties of PVA/HA composite bolus microspheres were characterized by Fourier infrared spectroscopy.Results:The PVA/HA composite embolization microspheres were internal, porous round spheres with a particle size distribution of 50-300 μm. The elastic properties of PVA/HA composite embolization microspheres were(13.6±0.145) kPa, which was 2.28 times that of PVA microspheres, and the drug loading capacity and encapsulation efficiency were (76.80±1.22) mg/g and (38.4±12.7)%, respectively. The maximum cumulative release rate of the microspheres within 7 days was (7.37±0.101)%, and the maximum cumulative release was (256.2±9.8) μg.Conclusions:PVA/HA composite embolization microspheres have good mechanical properties and drug-loading and drug-releasing properties, which provide an important reference for their use as medical devices.

Measurement and analysis of 90Y radioactivity in urine of patients treated with 90Y resin microspheres / 中华放射医学与防护杂志

Objective:To evaluate 90Y activity concentration in renal excretions during the first 48 hours after being treated with 90Y resin microspheres seleceive internal radiation therapy(SIRI) and to provide advice on the management of patient excreta after surgery. Methods:After surgery, urine excreted from 3 patients during 0-24 h and 24-48 h was collected respectively, and the 90Y activity concentration in urine was tested and analyzed. Results:90Y radioctivity in the urine excreted from 3 patients after surgery was (1 266±258)kBq/GBq during 0-24 h and (140±106) kBq/GBq during 24-48 h, respectively, and 90Y activity concentration were (640±113) kBq/L during 0-24 h and (53±12) kBq/L during 24-48 h. Conclusions:90Y radioactivity in patient′s urine excreted at 1 d was about 10 times higher than that at 2 d. After surgery, patients can accelerate the reduction of free 90Y activity by increasing excretion. Urine excreted by the patients during hospitalization should be handled in accordance with the requirements of the national standard HJ 1188-2021 Radiation protection and safety requirements for nuclear medicine.

Time-resolved fluorescence immunochromatographic assay for the detection of mycoplasma pneumoniae IgM and IgG / 中华核医学与分子影像杂志

Objective:To establish time-resolved fluorescence immunochromatographic assay (TFICA) for rapid and quantitative detection of mycoplasma pneumoniae (MP) immunoglobulin (Ig)M and IgG.Methods:Based on capillary effect and europium nanospheres, rapid TFICA for MP-IgM and IgG detections were developed with the optimized parameters (coupling rates of antigens or antibodies to microspheres, dilution of labeled nanospheres, fixture concentrations on test line and serum dilutions). The methodological performances were estimated such as sensitivity, specificity, stability. By testing 55 healthy control samples, the reference values of TFICA were obtained. The reliability was evaluated by Kappa test from detecting sera of 88 cases (33 patients and 55 healthy controls) using TFICA and commercial kits by chemiluminescence immunoassays (CLA). Results:After screening the assay conditions, the mass ratios of mouse anti-human IgG and MP antigen with nanospheres were 1∶20 and 1∶100 respectively; the work dilutions of nanobeads conjugated with anti-human IgG and MP antigen were 1∶200 and 1∶100 respectively; the spraying concentrations of MP antigen and goat anti-human IgM were 0.5 and 1.0 g/L on the test line respectively, and the working dilutions of serum sample were both 1∶300. In the MP-IgM and IgG detections, the linear working ranges were (0.78-70.00)×10 3 relative unit (RU)/L and (0.17-200.00)×10 3 RU/L, while the sensitivities of the assays were 0.78×10 3 and 0.17×10 3 RU/L, respectively. No cross reactions were found with antithyroid peroxidase antibody, anticardiolipin antibody or thyroglobulin antibody. In these MP-IgM and IgG assays, the relative standard deviations were 3.7%-14.8% and 2.9%-14.0%, the average reduction rates of fluorescence were 13.7% and 14.2% respectively after incubation at 37 ℃ for 5 d. The reference values of MP-IgM and IgG were 3.33×10 3 and 2.61×10 3 RU/L, while the Kappa values between TFICA and CLA were 0.79 and 0.76, respectively. Conclusion:TFICA is a simple, sensitive, specific and quantitative method for detecting MP-IgM and IgG antibodies, and may show great promise for future clinical use.

Radiological protection detection and dose assessment of selective internal radiotherapy with 90Y resin microspheres / 中华放射医学与防护杂志

Objective:To conduct radiation detection and dose assessment in selective internal radiotherapy with 90Y resin microspheres for the purpose of providing a reference for radiological protection. Methods:The dose rates from radiotherapy with 90Y resin microspheres were detected in the process of each operation at different distances from the body surface of patients the levels of dose to the persons concerned were compared with the relevant national regulations and standards. Results:The estimated dose rates were 1.12-454 μSv/h during 90Y resin microspheres dispensing and 2.06-58.2 μSv/h during surgical procedure. The dose rates at 0.5 h after surgery were 22.7-64.1 μSv/h at 5 cm and 0.82-2.55 μSv/h at 1 m from three patient′s body surface. Assuming treating 200 patients a year, the annual individual effective dose to the radiation workers was 0.12-1.03 mSv/year. The annual individual effective dose to the public, comforters and carers of patients was 0.02-0.24 mSv/year after release of a patient. Conclusions:During the treatment, nursing and release of patients, the radiation doses to workers, carers and the public are lower than the individual dose limit given in the GB18871-2002 basic standards for protection against ionizing radiation and for the safety of radiation sources and the management target value set by of the relevant medical institutions.

Strategies of microspheres and in situ forming gel implants in long-acting and research progress in controlling burst release / 中国药科大学学报

@#Long-acting injectables(LAIs) play an important role in the field of drug preparation research because they can control drug release for a long time and decrease dosing frequency. In this review, two types of LAIs, including injectable microspheres and in situ forming gel implants, were used as the breakthrough point to analyze the strategies and technologies used in the formulation and process to achieve long-acting drug release.At the same time, in view of the common burst release phenomenon, the relevant coping strategies in the current research were summarized, which provides some reference for the design, development and optimization of such long-acting preparations.

Microcápsulas y microesferas: una visión a la caracterización integral y aplicación para la liberación de medicamentos biotecnológicos / Microcapsules and microspheres: A vision to integral characterization and applications for biotechnological drugs delivery

Resumen Los microacarreadores basados en microcápsulas y microesferas han sido ampliamente estudiados y ensayados para controlar la liberación de medicamentos biotecnológicos (MB), disminuyendo la dosificación o modificando la vía de administración. Los métodos para la obtención de microacarreadores, son complejos y variados, por lo que es necesario determinar los requisitos mínimos que debe cumplir el sistema. El objetivo de este trabajo fue establecer las principales características que deben ser evaluadas en los microacarreadores para garantizar que la actividad biológica de los medicamentos biotecnológicos permanezca intacta a través del proceso de microencapsulación y, por lo tanto, que la seguridad del MB (desarrollo de reacciones inmunes) se mantenga inalterada. Las características a evaluar de un microacarreador deben describir las propiedades del material, tamaño y forma del sistema, carga de la partícula, funcionalidad, eficiencia de la microencapsulación y la cinética de liberación. Mientras que la integridad de los MB puede ser evaluada a partir de parámetros críticos de calidad: estructura y función biológica del MB, pureza del producto, presencia de agregados de alto peso molecular, estructura de orden superior y ensayos de actividad biológica. La caracterización de los microacarreadores debe enfocarse en la seguridad del biopolímero y proteínas ensayadas.

Abstract Microcarriers based on microcapsules and microspheres have been widely studied and tested to control the release of biotechnological drugs (BD), diminishing the dosage or modifying the route of administration. The methods for obtaining microcarriers are complex and varied, so it is necessary to determine the minimum characteristics with which the system must comply. The aim of this work was to establish the main characteristics that should be evaluated in the microcarriers in order to guarantee that the biological activity of biotechnological drugs remains intact through the microencapsulation process, and therefore the safety of the BD (development of immune reactions) remains unaltered. The characteristics of a microcarrier to be evaluated must describe the properties of the material, the size and shape of the system, the particle load, functionalization, the microencapsulation efficiency, and the kinetics of liberation. Whereas the integrity of BD can be evaluated by critical quality parameter such as: structure and biological function of the BD, product purity, presence of high molecular weight aggregations, higher order structure and biological activity tests. The characterization of the microcarriers must focus on the safety of the biopolymer and proteins tested.

Regenerative potential of basic fibroblast growth factor contained in biodegradable gelatin hydrogel microspheres applied following vocal fold injury: Early effect on tissue repair in a rabbit model / Potencial regenerativo do fator básico de crescimento de fibroblastos contido em microesferas biodegradáveis de hidrogel de gelatina aplicadas após lesão de prega vocal: efeito inicial no reparo tecidual em modelo de coelho

Abstract Introduction Postoperative dysphonia is mostly caused by vocal fold scarring, and careful management of vocal fold surgery has been reported to reduce the risk of scar formation. However, depending on the vocal fold injury, treatment of postoperative dysphonia can be challenging. Objective The goal of the current study was to develop a novel prophylactic regenerative approach for the treatment of injured vocal folds after surgery, using biodegradable gelatin hydrogel microspheres as a drug delivery system for basic fibroblast growth factor. Methods Videoendoscopic laryngeal surgery was performed to create vocal fold injury in 14 rabbits. Immediately following this procedure, biodegradable gelatin hydrogel microspheres with basic fibroblast growth factor were injected in the vocal fold. Two weeks after injection, larynges were excised for evaluation of vocal fold histology and mucosal movement. Results The presence of poor vibratory function was confirmed in the injured vocal folds. Histology and digital image analysis demonstrated that the injured vocal folds injected with gelatin hydrogel microspheres with basic fibroblast growth factor showed less scar formation, compared to the injured vocal folds injected with gelatin hydrogel microspheres only, or those without any injection. Conclusion A prophylactic injection of basic fibroblast growth factor -containing biodegradable gelatin hydrogel microspheres demonstrates a regenerative potential for injured vocal folds in a rabbit model.

Resumo Introdução A disfonia pós-operatória é causada principalmente por cicatrizes nas pregas vocais. Tem sido relatado que o manejo cuidadoso da cirurgia das pregas vocais reduz o risco de formação de cicatriz. No entanto, a depender da lesão da prega vocal, o tratamento da disfonia pós-operatória pode ser desafiador. Objetivo Desenvolver uma nova abordagem regenerativa profilática para o tratamento de pregas vocais lesionadas após a cirurgia, com microesferas biodegradáveis de hidrogel de gelatina como sistema de administração de medicamentos para o Fator Básico de Crescimento de Fibroblastos (bFGF). Método A cirurgia laríngea videoendoscópica foi feita para criar lesão nas pregas vocais em 14 coelhos. Imediatamente após esse procedimento, microesferas biodegradáveis de hidrogel de gelatina com bFGF foram injetadas na prega vocal. Duas semanas após a injeção, as laringes foram excisadas para avaliação da histologia das pregas vocais e do movimento da mucosa. Resultados A presença de função vibratória deficiente foi confirmada nas pregas vocais lesionadas. A histologia e a análise de imagem digital demonstraram que as pregas vocais lesionadas injetadas com microesferas de hidrogel de gelatina com bFGF apresentaram menor formação de cicatriz, em comparação com as pregas vocais lesionadas injetadas apenas com microesferas de hidrogel de gelatina ou aquelas sem injeção. Conclusão Uma injeção profilática de microesferas biodegradáveis de hidrogel de gelatina com bFGF demonstra um potencial regenerativo para pregas vocais lesionadas em um modelo de coelho.

A cost-effect analysis of transarterial chemoembolization with CalliSpheres beads loaded with arsenic trioxide versus arsenic trioxide iodized oil emulsion in treatment of unresectable liver cancer / 临床肝胆病杂志

Objective To investigate the cost-effect of transarterial chemoembolization (TACE) with CalliSpheres beads loaded with arsenic trioxide (ATO) (CBATO) versus ATO iodized oil emulsion (conventional TACE, cTACE) in the treatment of unresectable liver cancer. Methods A total of 100 patients with advanced liver cancer who attended The First Affiliated Hospital of Zhengzhou University from May 2017 to December 2018 were enrolled and divided into CBATO group( n =45) and cTACE group( n =55) according to the treatment regimen. Progression-free survival (PFS) was used to evaluate the efficacy of quality-adjusted life year (QALY), and European Quality of Life-5 Dimensions (EQ-5D) index was used to evaluate quality of life. The t -test was used for comparison of continuous data between groups, and the chi-square test was used for comparison of categorical data between groups; the number of surgeries, length of hospital stay, treatment cost, and incremental cost-effectiveness ratio (ICER) were calculated for the two groups, and then a cost-effect analysis was performed. Results Within the PFS time, the per capita hospital cost was 96 446 yuan in the CBATO group and 91 230.43 yuan in the cTACE group. There were significant differences between the two groups in the mean number of surgeries (2.5±0.7 vs 3.4±0.8, t =16.911, P < 0.01) and mean hospital stay (5.8±1.2 days vs 7.5±1.8 days, t =12.459, P < 0.01). The CBATO group had a significantly higher QALY than the cTACE group (0.804 vs 0.512). Compared with the cTACE group, the CBATO group had an ICER of 17 861.53 yuan/QALY for unresectable liver cancer. Conclusion Although CBATO has a higher surgery cost than cTACE, CBATO has a better clinical effect than cTACE and can reduce the number of surgeries and length of hospital stay, with a better postoperative quality of life than cTACE, suggesting that CBATO has marked cost-effect advantages.

Therapeutic effect of celecoxib-loaded microspheres on rheumatoid arthritis in rats after intra-articular injection / 中国药科大学学报

@#This study sought to assess the therapeutic effect of celecoxib (CEL)-loaded polylactic acid-glycolic acid copolymer (PLGA) microspheres on rheumatoid arthritis in rats after intra-articular injection.The celecoxib-loaded microspheres (CEL-MS) were prepared by the O/W solvent volatilization method with PLGA as carrier.In order to investigate the therapeutic effect of CEL-MS on rheumatoid arthritis in rats after intra-articular injection, a rat model of adjuvant arthritis (AA) was constructed by complete Freund''s adjuvant, and the evaluation indicators of the therapeutic effect were rat paw swelling, arthritis index,spleen index and joint synovial histopathological examination. The results showed that the microspheres had a smooth spherical morphology with a particle size of (2.1 ± 0.3) μm and a drug loading efficiency of (20.8 ± 0.6)%.The results of the in vivo efficacy test showed that intra-articular injection of CEL-MS compared to the CEL suspension oral and the celecoxib suspension intra-articular injection in adjuvant arthritis rat model can significantly reduce joint swelling and arthritis index, thus effectively inhibiting synovial inflammation.The above results indicate that intra-articular injection of CEL-MS has a good therapeutic effect on rheumatoid arthritis in rats.

Efficacy and safety of CalliSpheres microsphere versus conventional transcatheter arterial chemoembolization in treatment of hepatocellular carcinoma: A Meta-analysis / 临床肝胆病杂志

ObjectiveTo investigate the efficacy and safety of CalliSpheres microsphere-transcatheter arterial chemoembolization (CSM-TACE) versus conventional transcatheter arterial chemoembolization (cTACE) in the treatment of hepatocellular carcinoma (HCC) through a meta-analysis. MethodsPubMed, Web of Science, Cochrane Library, CNKI, Wanfang Data, and VIP were searched for all Chinese and English articles on the application of CSM-TACE and cTACE in HCC published up to the end of October, 2020. After quality assessment was performed for the articles included, RevMan 5.3 software provided by Cochrane Library was used for analysis. ResultsA total of 15 studies were included, with 1535 patients in total. This meta-analysis showed that compared with the patients receiving cTACE, the patients receiving CSM-TACE had significantly higher 1-year overall survival rate (odds ratio ［OR］=2.26, 95% confidence interval ［CI］: 1.63-3.13, P＜0.000 01), 2-year overall survival rate (OR=1.73, 95%CI: 1.20-2.50, P=0.003), and 2-year progression-free survival rate (OR=1.60, 95%CI: 1.05-2.43, P=0.03). In terms of safety, compared with the patients receiving cTACE, the patients receiving CSM-TACE had significantly lower incidence rates of postoperative vomiting (OR=0.65, 95%CI: 0.46-0.92, P=0.01), bone marrow suppression (OR=0.17, 95%CI: 0.05-0.54, P=0.003), and neutropenia (OR=0.18, 95%CI: 0.07-045, P=0.000 3), while there were no significant differences between the two groups of patients in postoperative pyrexia, abdominal pain, and ascites (all P＞0.05). ConclusionCSM-TACE has significant advantages in improving 1- and 2-year overall survival rates and 2-year progression-free survival rates and can significantly reduce the incidence rates of postoperative vomiting, bone marrow suppression, and neutropenia. Therefore, CSM-TACE is a safe and effective treatment method.

Research progress in new formulations of norcantharidin / 药学实践杂志

Objective To review the research progress in new formulations of norcantharidin. Methods The foreign and domestic literature search in the new formulations of norcantharidin was conducted. The research and development of norcantharidin formulations were summarized and commented. Results The drug delivery systems, such as microspheres, nanoparticles, liposomes, and microemulsions, have great development potential as the new formulations for norcantharidin. Conclusion Norcantharidin is an excellent anti-tumor drug. The traditional injections and tablets have serious side effects in clinical application. The new formulations reduced the renal and urinary toxicity and side effects. Those formulations provided better therapeutic effects as target medication. Therefore, the new norcantharidin formulations have great development prospects.

Fabrication of potential gastroretentive microspheres of itraconazole for stomach-specific delivery: Statistical optimization and in vitro evaluation

The premise of the study was to develop and optimize multiple unit gastroretentive microspheres of itraconazoleto prolong its localization in the stomach and analyzed using response surface methodology. The emulsion solventdiffusion evaporation method was used to prepare hollow microsphere of ethyl cellulose and Eudragit RS100 as lowdensity shell-forming polymers. The experimental design matrix was prepared using a central composite design tostudy the effect of various process parameters over response variables. The optimized microspheres showed a particlesize of 285.1µm, drug entrapment efficiency of 86.8%, buoyancy of 51.1%, and cumulative drug release of 77.80%.The experimental responses were in good harmony with the predicted values. The compatibility between drug andexcipients was determined by Fourier-transform infrared and differential scanning calorimetry analysis. The resultssignify that gastroretentive hollow microspheres are a promising vehicle to extend the retention time of itraconazolein the upper GI tract, and it can be floated in an acidic medium for a prolonged period.

Construction of periodontal biomimetic membrane with electrospun poly(Lactic-co-glycolic acid) nanofibers and electrosprayed chitosan microspheres / 中国组织工程研究

BACKGROUND: When the teeth are separated from the alveolar fossa, the periodontal membrane breaks, and the residual periodontal membrane on the avulsed tooth root surface changes from three-dimensional to two-dimensional, thus losing the role of scaffold, and leading to root bone adhesion after replantation of avulsed tooth. How to develop a three-dimensional sustained-release scaffold material that can adhere to the root surface with a certain thickness and strength is one of the key factors for successful regeneration of avulsed tooth periodontal membrane. OBJECTIVE: To construct a three-dimensional periodontal biomimetic membrane that can adhere to the avulsed tooth root surface and allow sustained-release of growth factors. METHODS: Poly(lactic-co-glycolic acid) (PLGA) membrane was prepared using electrospinning technique. The effects of dichloromethane and dimethylformamide mixture, hexafluoroisopropanol, and trichloromethane on electrospun membrane were investigated to obtain the optimal electrospinning solvent. Chitosan microspheres were prepared by electrospray and ion cross-linking techniques. The effects of molecular weight (50, 000, 100, 000) and mass concentration (10, 20 g/L) of chitosan, sodium tripolyphosphate concentration (2%, 5%, 10%) and voltage (14, 28 kV) on chitosan microspheres were studied to screen the optimum parameters. Chitosan microspheres containing stromal cell-derived factor-1 (optimal parameter design) were constructed. The release rate of stromal cell-derived factor-1 alpha in vitro was determined. First, the root surface of teeth was wrapped with electrospun PLGA membrane, then chitosan microspheres were dripped on the surface, and finally the surface was wrapped with a thin layer of electrospun PLGA. Thus, PLGA-chitosan-PLGA biomimetic membrane was constructed. RESULTS AND CONCLUSION: Electrospun PLGA membrane prepared with hexafluoroisopropanol as electrospinning solvent had the smallest average diameter and the largest porosity. When the relative molecular weight of chitosan was 50, 000 and the mass concentration was 20 g/L, the size of chitosan microspheres was basically the same, and the average diameter was 366. 6 μm. In addition, chitosan microsphere had good monodispersity, fullness, and stability. Chitosan microspheres formed under 28 kV voltage and were more in line with the requirements of biomimetic membrane for avulsed tooth. The surface of microspheres prepared by 5% sodium tripolyphosphate had medium-sized pores, which are most conducive to clinical periodontal membrane regeneration. Chitosan microspheres can sustainably release stromal cell derived factor 1alpha for about 1 month. In this study, we constructed a three-dimensional PLGA-chitosan-PLGA periodontal biomimetic membrane that can adhere to the avulsed tooth root surface and allow sustained-release of growth factors and obtained the optimal parameters of constructing the periodontal biomimetic membrane. Based on the PLGA-chitosan-PLGA periodontal biomimetic membrane, the effect and mechanism of tissue engineering on replantation of avulsed tooth can be further studied.

Nerve conduits of chitosan/polyvinyl alcohol with brain-derived neurotrophic factor microspheres for peripheral nerve defects in rats / 中国组织工程研究

BACKGROUND: The repair of peripheral nerve defects by nerve conduit bridging can provide a suitable microenvironment for nerve regeneration. On one hand, it can provide a unique channel for nerve regeneration, prevent the invasion of peripheral connective tissue and the formation of scars. On the other hand, it can maintain endogenous and exogenous neurotrophic factors, growth factors and other stimulants to promote axon growth. OBJECTIVE: To observe the therapeutic effect of chitosan/polyvinyl alcohol catheter injected with brain-derived neurotrophic factor sustained-release microspheres to bridge peripheral nerve defects. METHODS: Chitosan/polyvinyl alcohol nerve conduit was prepared by repeated freeze-thaw technique. The brain-derived neurotrophic factor microspheres were obtained by polymer-alloys combined with oil-oil emulsion/solvent evaporation method. A 15 mm sciatic nerve defect model was made in the right hindlimb of 60 adult male Sprague-Dawley rats. They were selected and randomly divided into four groups (n=15 per group): group A implanted with autogenous sciatic nerve; group B implanted with chitosan/polyvinyl alcohol nerve catheter, injected with normal saline; group C implanted with chitosan/ polyvinyl alcohol nerve catheter, injected with brain-derived neurotrophic factor solution; group D implanted with chitosan/polyvinyl alcohol nerve catheter, injected with brain-derived neurotrophic factor sustained-release microspheres. General observation, histological inspection, and electrophysiological determination were performed at 4 months after the surgery. This study was approved by the Research Ethics Committee of the Second Hospital of Hebei Medical University. RESULTS AND CONCLUSION: (1) Gross anatomy showed that muscle atrophy in group A and group D was lighter than that in the other two groups. The grafts in four groups were all adhered to the peripheral tissues, and the nerve in the autotransplantation segment was strongly adhered to the peripheral tissues. In group D, the regenerated nerve had connected the distal and proximal nerves, and the regenerated nerve filled the conduit. (2) Electrophysiological examination showed that the latency of group D was shorter than that of groups B and C (P 0.05). (3) Histological observation showed that there were regenerated nerve fibers in groups B, C, and D. The diameter, number and thickness of myelin sheath of group D were larger than those of group B and group C (P 0.05). (4) The results showed that the injection of brain-derived neurotrophic factor microspheres into chitosan/PVA catheter had a long-term promoting effect on peripheral nerve regeneration.