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.

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.

Tratamiento de lesiones apicoperirradiculares con un biomaterial de tercera generación (Licon-D) / Treatment of apicoperiradicular lesions with a third-generation biomaterial (Licon-D)

Biomaterial de tercera generación con una tasa de degradabilidad en la zona perirradicular y del foramen apical, con una velocidad similar a la que emplea el organismo para formar tejido calcificado y sellar biológicamente el extremo apical del diente. Mediante el recurso tecnológico de la microencapsulación se produce la liberación lenta y controlada de Ca2+ retenido en la superficie y en el interior de las microesferas de alginato de calcio, sin que se modifique de manera significativa las propiedades reológicas básicas del biomaterial de obturación de conductos, tales como la compresibilidad, plasticidad, extensibilidad, fluidez, viscosidad cinemática, viscosidad de compresión y endurecimiento por trabajo (AU)

Third-generation biomaterial with a degradability rate in the periradicular area and the apical foramen, with a speed similar to that used by the body to form calcified tissue and biologically seal the apical end of the tooth. Through the technological resource of microencapsulation, the slow and controlled release of Ca2+ retained on the surface and inside the calcium alginate microspheres is produced, without significantly modifying the basic rheological properties of the duct sealing biomaterial, such as compressibility, plasticity, extensibility, flowability, kinematic viscosity, compression viscosity, and work hardening (AU)

Chinese expert consensus on selective internal radiation therapy with yttrium-90 for primary and metastatic hepatocellular carcinoma / 中华肝脏病杂志

Liver malignant tumors are one of the most common causes of cancer-related deaths in China. Selective internal yttrium-90 radioembolization therapy ((90)Y-SIRT) is a kind of promising local minimally invasive method, and its effectiveness and safety has been confirmed in clinical application over the past two decades. Moreover, it has been approved by the U.S. National Comprehensive Cancer Network and other international guidelines for the topical treatment of patients with liver malignancies. Taking into account the complexity of the (90)Y-SIRT and the need for multidisciplinary collaboration to improve the safety and success rate of treatment, the Nuclear Medicine Expert Committee of the Chinese society of Clinical Oncology, along with Beijing Nuclear Medicine Quality Control and Improvement Center invited experts from surgical oncology, interventional medicine, nuclear medicine, and other related fields to discuss and form a consensus on the clinical diagnosis, treatment and management, which mainly included definition, indications and contraindications, treatment procedures, postoperative follow-up, adverse reactions and complications, radiation safety management, etc. Herein, we provide the reference guidance to establish (90)Y-SIRT standardized management and treatment system various units for relevant practitioners.

Preparation of different fragments of SARS-CoV-2 N protein and its application in fluorescence chromatography / 生物工程学报

Different fragments of SARS-CoV-2 nucleocapsid (N) protein were expressed and purified, and a fluorescence immunochromatography method for detection of SARS-CoV-2 total antibody was established. The effect of different protein fragments on the performance of the method was evaluated. The N protein sequence was analyzed by bioinformatics technology, expressed in prokaryotic cell and purified by metal ion affinity chromatography column. Different N protein fragments were prepared for comparison. EDC reaction was used to label fluorescence microsphere on the synthesized antigen to construct sandwich fluorescence chromatography antibody detection assay, and the performance was systemically evaluated. Among the 4 prepared N protein fragments, the full-length N protein (N419) was selected as the optimized coating antigen, N412 with 0.5 mol/L NaCl was used as the optimal combination; deleting 91-120 amino acids from the N-terminal of N412 reduced non-specific signal by 87.5%. the linear range of detection was 0.312-80 U/L, the limit of detection was 0.165 U/L, and the accuracy was more than 95%. A fluorescence immunochromatographic detection method for analysis of SARS-CoV-2 total antibody was established by pairing N protein fragments. The detection result achieved 98% concordance with the commercially available Guangzhou Wanfu test strip, which is expected to be used as a supplementary approach for detection of SARS-CoV-2. The assay could also provide experimental reference for improving the performance of COVID-19 antibody detection reagents.

Controlled release alginate-chitosan microspheres of tolmetin sodium prepared by internal gelation technique and characterized by response surface modeling

Tolmetin sodium (TS) is a powerful non-steroidal mitigating drug for the treatment of rheumatoid joint inflammation, osteoarthritis, and adolescent rheumatoid joint pain. In addition to its gastrointestinal (GIT) problems, TS has a short biological half-life (1 hr). In a trial to overcome these side effects and control the rate of (TS) release, chitosan coated alginate microspheres are recommended. A Box-Behnken experimental design was employed to produce controlled release microspheres of TS in the sodium alginate and chitosan copolymers (Alg-Ch) by emulsification internal gelation methodology. The effect of critical formulation variables namely, drug to polymer ratio (D:P ratio), speed of rotation and span 80% on drug encapsulation efficiency (% EE), drug release at the end of 2 hours (Rel2) and drug release at the end of 8 hours (Rel8) were analyzed using response surface modeling. The parameters were assessed using the F test and mathematical models containing only the significant terms were generated for each parameter using multiple linear regression analysis. The produced microspheres were spherical in shape with extensive pores at D:P ratio 1:1 and small pores at a drug to polymer ratio (D:P ratio) 1:3. Differential scanning calorimetry (DSC) affirmed the steady character of TS in microspheres and revealed their crystalline form. All formulation variables examined exerted a significant influence on the drug release, whereas the speed emerged as a lone factor significantly influencing % EE. Increasing the D: P ratio decreases the release of the drug after two and 8 hours. The increase in speed results in an increase in drug release after two and eight hours. The drug release from the microspheres followed zero order kinetics. TS Alg-Ch microspheres exhibited a significant anti-inflammatory effect on incited rat paw edema after eight hours. These results revealed that the internal gelation technique is a promising method to control TS release and eradicate GIT side effects using Alg-Ch copolymers.

Preparation and in vitro release profiling of PLGA microspheres containing BSA as a model protein

Conventional drug formulations are incapable of adequate delivery of proteins and peptides for therapeutic purposes. As these molecules have very short biological half-life, multiple dosing is required to achieve the desirable therapeutic effects. Microspheres are able to encapsulate proteins and peptide in the polymeric matrix while protecting them from enzymatic degradation. In this study Bovine Serum Albumin (BSA) matrix type microspheres were fabricated using Polylactide-co-glycolide (PLGA) by double emulsion solvent evaporation method. The effects of variables such as homogenizer speed, molecular weight of polymer and the effect of pH of the water phases, were investigated against factors such as drug loading, encapsulation efficiency, morphology, size, drug distribution and release profile of the microspheres. Results, suggested that an increase in homogenization speed leads to a decrease in microsphere size. The increase in homogenization speed also caused a significant effect on the release profile only when higher molecular weight of polymer had been used.. The pH change of the internal aqueous phase led to modification of surface morphology of spheres to a porous structure that significantly increased the total amount of released protein. Integrity of protein structure was intact as shown by SDS-PAGE. According to the results, it can be concluded that we achieved a reproducible method regarding controlled protein delivery for different sizes of particles.

Tadalafil-loaded PLGA microspheres for pulmonary administration: preparation and evaluation

Tadalafil, a long-acting PED-5 inhibitor, is commonly used for the treatment of pulmonary arterial hypertension (PAH). However, its efficacy and clinical application are severely limited by the poor water solubility, low bioavailability and a series adverse effects (e.g. headaches, indigestion). In this study, tadalafil was prepared and loaded into biodegradable PLGA (poly(lactic-co-glycolic acid)) microspheres (TDF-PLGA-MS) via emulsification-solvent evaporation. The resulting microspheres were processed into pulmonary inhalant by freeze drying. The TDF-PLGA-MS was spherical and uniform, with an average particle diameter ~10.29 µm. The encapsulation efficiency and drug loading yield of TDF-PLGA-MS were 81.68% and 8.52%, respectively. The investigation of micromeritics showed that the TDF-PLGA-MS had low moisture content. The fluidity of powders was relatively good. The aerodynamic diameter and emptying rate of microspheres powders were 3.92 µm and 95.41%, respectively. Therefore, the microspheres powders were easy to be atomized, and can meet the requirements of pulmonary administration. In vitro release results showed that the microspheres group released slowly. The cumulative release in 24 h and 10 d was 46.87% and 84.06%, respectively. The in vitro release profile of TDF-PLGA-MS was in accordance with the Weibull model. The results of Pharmacokinetics showed that tadalafil from microspheres slowly released into the blood after intratracheal instillation. The pulmonary drug residue in 0.5 h was 3.5 times compared with solution group. The residual concentration in lung after 10d was still higher than that of solution group in 48 h. The t1/2β and MRT0-∞ were 3.10 times and 3.96 times that of solution group, respectively. Moreover, the Cmax and AUC of drug residues in lung ​​were 3.48 times and 16.36 times that of solution group, respectively. The results of tissue distribution showed that the Re in lung was 16.358, which indicated the lung targeting. In conclusion, the TDF-PLGA-MS for pulmonary administration in this study can significantly improve the pulmonary targeting, increase efficacy of tadalafil and reduce other non-target organs toxicity. This study will have an important clinical significance for PAH patients who need long-term drug therapy.

The efficacy of sustained-release chitosan microspheres containing recombinant human parathyroid hormone on MRONJ

Abstract Treatment of patients with bisphosphonate usage is a significant concern for oral surgeons because it interferes with jaw bone turnover and regeneration. In case of adverse effects manifesting related to bisphosphonate use, oral surgeons are usually treating and keep the patient's symptoms under control. In this study, we aimed to investigate a new treatment protocol for medication-related osteonecrosis of the jaw (MRONJ). This treatment protocol consisted of administering human parathyroid hormone (hPTH) loaded chitosan microspheres which were prepared by ionotropic gelation method or/and the prepared microspheres were suspended in a poloxamer gel. After in-vitro optimization studies, the efficacy of the chosen formulations was evaluated in-vivo studies. Zoledronic acid was administered daily to forty-eight adult female Sprague-Dawley rats, divided into four experimental groups, at a daily concentration of 0.11 mg/kg over three weeks to induce the MRONJ model. At the end of this period, maxillary left molar teeth were extracted. In the first group, the subjects received no treatment. In the negative control group, poloxamer hydrogel containing empty microspheres were immediately applied to the soft tissues surrounding the extraction socket. The treatment group-1 was treated with local injections of poloxamer hydrogel containing hPTH. The treatment group-2 was treated with a single local injection of poloxamer hydrogel containing hPTH-loaded chitosan microspheres. Both treatment groups received a total of 7 µg of hPTH at the end of the treatment protocol. Our study demonstrates successful attenuation of MRONJ through a local drug delivery system combined with hPTH, as opposed to previously attempted treatment strategies.

Preparation and characterization of paclitaxel microspheres in situ gel and its antitumor efficacy by local injection / 北京大学学报(医学版)

OBJECTIVE@#The current difficulties in the treatment of tumor include repeated administration and high recurrence rate after tumor resection. In order to reduce the number of doses, avoid side effects of chemotherapeutic drugs, suppress tumor growth and delay tumor recurrence after surgery, a temperature-sensitive in situ gel with paclitaxel microspheres (PTX/M gel) was prepared. PTX/M gel was administered by intratumoral injection once a month.@*METHODS@#First of all, paclitaxel microspheres (PTX/M) were prepared by emulsion solvent evaporation method. A laser particle size distribution analyzer was used to investigate the size, distribution, specific surface area of microspheres. Paclitaxel content was determined by high performance liquid chromatography (HPLC). Then encapsulation efficiency of paclitaxel was calculated and in vitro release characteristics were studied. Secondly, PTX/M gel was prepared by cold dissolution method. The phase transition temperature, elastic modulus, dissolution curve, correlation between dissolution and release were measured. Finally, U87 MG and 4T1 subcutaneous tumor models were established respectively to study the efficacy of PTX/M gel in suppressing tumor growth and delaying tumor recurrence after surgery.@*RESULTS@#The median diameter of the selected PTX/M was (32.24±1.09) μm, the specific surface area was (206.61±10.23) m2/kg, the encapsulation efficiency was 85.29%±1.34%, and the cumulative release percentage of paclitaxel from PTX/M was 33.56%±3.33% in one month. Phase transition temperature of PTX/M gel was 33 °C. The elastic modulus of PTX/M gel at 25 °C and 37 °C were 4.2×103 Pa and 18×103 Pa, respectively. The gel could stay in the body for up to 48 hours. It could be seen from the results of animal experiments that were compared with the saline group and the Taxol group, and the tumor-bearing mice of the PTX/M gel group had the slowest tumor growth (P<0.05). Similarly, in the tumor recurrence experiments, the mice of PTX/M gel group had the latest tumor recurrence after surgery.@*CONCLUSION@#As a local sustained-release preparation, PTX/M gel can effectively suppress tumor growth and delay postoperative recurrence of tumors. It has potential advantages in tumor treatment.

Effects of three drying methods on the physical properties and drug delivery in chitosan microspheres / 华西口腔医学杂志

OBJECTIVE@#The purpose of this study is to investigate the effects of different drying methods on the physical properties and drug delivery of chitosan microspheres.@*METHODS@#Three types of drying methods were utilized, including air drying and freeze drying after freezing at -20 ℃ (slow cooling) and at -80 ℃ (fast cooling). The physical properties of microspheres were characterized. Utilizing bovine serum albumin (BSA) as the model drug, the in-vitro release behaviors of drug-loaded beads were investigated.@*RESULTS@#By comparing the physical properties of the different drying methods, the microspheres' diameters, porosities, and surface area were observed to increase successively from air drying and slow cooling to fast cooling, whereas the pore size and the swelling and degradation rates varied. The drug-loading experiments revealed that the loading capacity of air-dried microspheres was the lowest and the release rate was the slowest. Although the loading capacity of fast cooling microspheres was high, an obvious burst release was observed. The loading capacity of slow cooling microspheres was similar to that of the fast cooling microspheres and the loaded BSA can be released continuously.@*CONCLUSIONS@#The results indicate that different drying methods can affect the physical properties of chitosan microspheres, which further influence drug loading and release.

Update on Transarterial Chemoembolization with Drug-Eluting Microspheres for Hepatocellular Carcinoma

Conventional transcatheter arterial chemoembolization (c-TACE) is a widely used first-line palliative treatment for patients with unresectable hepatocellular carcinoma (HCC). Despite the effectiveness of c-TACE, to date, technique and procedure scheduling has not yet been standardized. Drug-eluting microspheres (DEMs) were therefore introduced to ensure more sustained and tumor-selective drug delivery for permanent embolization. These DEMs can load various drugs and release them in a sustained manner over a prolonged period. This approach ensures the delivery of high concentrations of chemotherapeutic agents to tumors, without increasing systemic concentrations, and promote tumor ischemia and necrosis. This review summarizes the recent advances in the use of DEM-TACE to treat HCC.

Radioembolization for the Treatment of Primary and Metastatic Liver Cancers / 대한핵의학회잡지

Radioembolization using ⁹⁰Y microspheres (glass or resin) has been introduced as an effective intraarterial therapy for unresectable primary and metastatic liver cancers. Although the basic therapeutic effect of chemoembolization results from ischemia, the therapeutic efficacy of radioembolization comes from radiation. Furthermore, compared with surgical resection and local ablation therapy, radioembolization is available with less limitation on the sites or number of liver cancers. The radioisotope ⁹⁰Y is a β-radiation emitter without γ-radiation, with the emission of secondary bremsstrahlung photons and small numbers of positrons. Administration of ⁹⁰Y microspheres into the hepatic artery can deliver a high dose of radiation selectively to the target tumor with limited radiation exposure to the surrounding normal parenchyma, and has low systemic toxicity. In general, radioembolization has been considered for patients with unresectable primary or metastatic liver-only or liver-dominant cancers with no ascites or other clinical signs of liver failure, life expectancy of > 12 weeks, and good performance status. Here, we review the current radioactive compounds, pretreatment assessment, and indications for radioembolization in patients with hepatocellular carcinoma, intrahepatic cholangiocarcinoma, and liver metastases from colorectal cancer.

Efforts in the Formation and Development of Nuclear Medicine in Vietnam / 대한핵의학회잡지

The foundations of nuclear medicine in Vietnam were established from 1970. Until now, after 48 years of development, in Vietnam, we have some basic equipment including 31 SPECT, 4 SPECT/CT machines, 11 PET/CT scanners, five cyclotrons, and one nuclear reactor.Many nuclearmedicine techniques in diagnosis and treatment have been routinely performed at provincial and central level health facilities such as tumor scintigraphy, thyroid scintigraphy, bone scintigraphy, kidney scintigraphy, cardiac scintigraphy, and radio-isotope therapy with I-131 and P-32. Selective internal radiation therapy with Y-90 microsphere and I-125 radioactive seed implantation has been also successfully applied in some big hospitals. However, there are still many difficulties for Vietnam as the lack of new widely used radioisotopes such as Ga-67, Cu-64, Samarium-153, and Lutetium-177 and the lack of nuclear medicine specialists. In the future, we are putting our efforts on the applications of new isotopes in diagnosis and treatment of cancers (theranostic) like Ga-68-DOTATATE, Lutetium-177-DOTATATE, Ga-68-PSMA, and Lutetium-177-PSMA, equipping modern nuclear medicine diagnostic tools, strengthening the human resources training in nuclear medicine. At the same time, we are trying our best to strengthen the cooperation with international nuclear medicine societies in over the world.

Nuclear Theranostics in Turkey / 대한핵의학회잡지

Nuclear theranostics functions as a bridge which connects targeted diagnosis to targeted therapy, just like Turkey functions as a geographical bridge which connects Asia to Europe. This unique geographical site of the country plays an important role with regard to introduction of novel scientific and technologic improvements, which originate from one continent to another, in the era of accelerated information. The first nuclear medicine practice in Turkey started in the beginning of 1950s with the first radioiodine treatment, which actually was a debut for nuclear theranostics in Turkey, years before many other countries in the world. For the time being, along with radioiodine treatment, many other theranostic applications such as I-131 MIBG treatment, Lu-177/Y-90 DOTA peptide treatment, Lu-177 PSMA treatment, Y-90 microsphere treatment, and bone palliative treatment are being performed in many centers countrywide. As science and technology improves, novel theranostic applications are eagerly awaited to be introduced in near future. This paper summarizes the story of nuclear theranostics in Turkey and aims to give an overview on the current status of theranostic applications in Turkey.

Safety and efficacy of polycaprolactone copolymer nanosphere hydrogel injected into the scalp dermal tissue of rats

BACKGROUND: Currently, dermal fillers need to be 25 µm or larger to reduce in vivo degradation by macrophages. However, the large size of fillers may cause side effects, including interruption of blood flow and nodule formation. Therefore, using rats, we tested a polycaprolactone copolymer hydrogel with nanoscale particles that could maintain a low in vivo degradation rate. METHODS: Thirty-six 6-week-old Sprague-Dawley rats were divided into group A (normal saline), group B (polycaprolactone microsphere filler), and group C (polycaprolactone copolymer nanosphere hydrogel). The corresponding materials were injected into the dermal layer of the scalp of the rats. At 4, 8, and 12 weeks after injection, blood biochemical and kidney and liver histological analyses were performed. Tissues were examined using hematoxylin-eosin staining to observe tissue infiltration of materials. Collagen formation in the dermal tissue of the scalp was observed with Masson trichrome staining and the collagen content was quantified using a soluble collagen assay kit. RESULTS: The histologic examination for organ infiltration showed no abnormal findings. All blood test results were within the normal ranges. The amount of collagen at 12 weeks increased by 1.22 mg/g in group C and by 0.6 mg/g in group B. CONCLUSIONS: The results reveal that the nanosphere complex near the injection site induced collagen formation. Regardless of the sphere size, aggregation of the copolymer prevented macrophage phagocytosis. The polycaprolactone copolymer nanosphere hydrogel was effective for more than 3 months when injected in the scalp dermal tissue of Sprague-Dawley rats and can be used safely.

Preparation of aspirin sustained-release microsphere and its in vitro releasing property / 北京大学学报(医学版)

OBJECTIVE@#It has been proven that acetylsalicylic acid (aspirin), as a kind of classical non-steroidal anti-inflammatory drug, not only has the effect of anti-inflammatory, but also has the function of immunity regulation and mineralization. However, it needs further investigation to study how to delay release of aspirin for a long time and enable to promote bone regeneration. Herein, we demonstrated that the longterm delayed release pattern of aspirin through the construction of microsphere scaffolds is promising to achieve the excellent bone regeneration.@*METHODS@#Here we synthesized three kinds of scaffolds as follows: (1) aspirin loaded calcium silicate (CaSiO3) microsphere (CaSiO3-aspirin) via simple immersion; (2) aspirin loaded polylactic-co-glycolic acid (PLGA) microsphere (PLGA-aspirin) via oil/water (O/W) emulsion; (3) aspirin loaded PLGA-CaSiO3 scaffold (PLGA-CaSiO3-aspirin) via O/W emulsion, optimal morphology and structure of PLGA-CaSiO3-aspirin scaffold was acquired through modulating the ratio between PLGA and CaSiO3. Furthermore, spectrophotometer was used to monitor the concentration of the extract of the three scaffolds for different releasing time, including 1, 2, 4, 6, 9, 13, 17, 21, 24, 30, 36, and 45 days, aspirin loading efficiency and its accumulation releasing curves were both achieved according to the concentration of aspirin. Their sustained release effects of aspirin were evaluated eventually.@*RESULTS@#Environmental scanning electron microscope (ESEM) results showed that the surface structure of the three kinds of scaffolds were smooth and had uniform size distribution. In addition, a small amount of PLGA-aspirin microspheres occurred to aggregation, while a small amount of CaSiO3-aspirin microspheres were broken. Moreover, the PLGA-aspirin microspheres in the PLGA-CaSiO3-aspirin scaffolds were uniformly adhered to the surface of CaSiO3 microspheres. The aspirin loadings of CaSiO3-aspirin, PLGA-aspirin, and PLGA-CaSiO3-aspirin were (1.06±0.04)%, (7.05±0.06)%, and (6.75±0.18)%, respectively. In addition, their corresponding time for releasing 95% of aspirin was 3, 24, and 36 days, respectively. The releasing time of PLGA-CaSiO3-aspirin was longer than that of the others and the releasing rate was more stable.@*CONCLUSION@#The microsphere scaffold of PLGA-CaSiO3-aspirin composites has excellent delayedrelease effect on aspirin, which is promising for using as osteogenic materials.

Whitening toothpaste containing activated charcoal, blue covarine, hydrogen peroxide or microbeads: which one is the most effective?

Abstract The efficacy of whitening toothpastes is questionable and controversial. Clinicians, patients and researchers have expressed concern with whitening toothpastes due to the risk of wearing the dental structure and the potential for disappointment if the advertised cosmetic results are not achieved. Objective: This study compared the whitening performance of toothpastes with different whitening technologies after initial and continued use. Material and Methods: Ninety bovine incisors were stained using a concentrated solution of black tea. They were randomly distributed into 6 groups, according to the toothpaste whitening technology: activated charcoal (B&W), blue covarine (WAD), hydrogen peroxide (LWA), microbeads (Oral B 3D White Perfection - 3DW) and optimized abrasives (XW4D). They were compared to a traditional toothpaste without a whitening agent (TA - control). Specimens underwent a brushing machine with controlled pressure, time and temperature. A calibrated examiner measured the color using a VITA-Classical scale before the first brushing cycle (T0), after the first brushing cycle (TI), and after a brushing cycle that simulates continuous use (TCU). Whitening performance was evaluated by the difference of shades (ΔSGU) between T0-TI and T0-TCU timepoints, using the Kruskal-Wallis and Dunn's non-parametric test. The Wilcoxon test was used to evaluate the cumulative effect (α=0.05). Results: Statistically significant differences were observed between toothpastes in both TI and TCU (p<0.05). The time of use also had a significant effect (p<0.05). Conclusion: Only WAD and 3DW showed whitening performance after the first use (TI). The greatest whitening performance after continuous use was obtained by WAD, followed by LWA and 3DW. The use of conventional toothpaste (TA) promotes no tooth whitening. Clinical relevance: Microbead abrasives (3DW) and blue covarine (WAD) were the active technology tested that presented the best global tooth whitening performance.

Preparation and evaluation of blank and doxorubicin loaded poly (acrylic acid) microspheres for embolization / 北京大学学报(医学版)

OBJECTIVE@#To prepare ion exchange doxorubicin-loaded poly (acrylic acid) microspheres (DPMs) and evaluate the properties of these chemoembolic agents.@*METHODS@#Poly (acrylic acid) microspheres (PMs) without drug were prepared by inverse suspension polymerization method and then doxorubicin was loaded by ion exchange mechanism to prepare DPMs. Optical microscope was used to investigate the morphology and particle size distribution of PMs and DPMs; fluorescence microscope and confocal microscope were used to observe the distribution of doxorubicin after drug loading. Elasticities of both the microspheres were evaluated by texture analyzer. High performance liquid chromatography (HPLC) method was established to determine the drug loading behavior of PMs and releasing behavior of DPMs. The in vivo embolic property was evaluated by embolizing the hepatic artery of a rabbit with 0.1 mL of DPMs.@*RESULTS@#PMs and DPMs were both spherical in shape, smooth in surface and dispersed well. Doxorubicin was mainly in the outer area inside of DPMs and distributed evenly. The average particle size of PMs and DPMs were (283±136) μm and (248±149) μm, respectively. PMs and DPMs both had good compression ability with the Young's modulus of (62.63±1.65) kPa and (93.94±1.10) kPa separately. PMs reached the drug loading balance at 12 h, and the entrapment efficiency was greater than 99%. Drug loading of PMs in doxorubicin solution at the concentration of 5.0 g/L and 12.5 g/L was (19.78±0.27) g/L and (49.45±0.37) g/L, respectively. Doxorubicin released slowly from DPMs in PBS and the accumulative release percentages of DPMs with corresponding drug loading were 6.82%±0.02% and 2.83%±0.10% after 24 h, respectively. Arterial angiograms showed that the hepatic artery of the rabbit was successfully embolized with DPMs.@*CONCLUSION@#DPMs with good performance of loading doxorubicin could be a potential embolic agent for transcatheter arterial chemoembolization.

Formulation development and evaluation of gastroretentive floating beads with Brucea javanica oil using ionotropic gelation technology / 中国天然药物

In the present study, a gastric retention floating system for Brucea javanica oil, composed of alginate and carrageenan, was prepared using ionotropic gelation. Parameters for floatability, drug load, encapsulation efficiency, bead morphology, in vitro release, and in vivo gastric retention were evaluated. The optimized formulation via Box-Behnken design consisted of 1.7% alginate (W/V), 1.02% carrageenan (W/V), 1.4% CaCO (W/V), and a gelling bath of pH 0.8. The alginate-carrageenan-Brucea javanica oil beads had a porous structure and exhibited up to 24 h of in vitro floatability with a load capacity of 45%-55% and an encapsulation efficiency of 70%-80%. A 6-h sustained release was observed in vitro. The beads had a prolonged gastric retention (> 60% at 6 h) in fasted rats, compared to non-floating beads (15% at 6 h), as measured by gamma scintigraphy with single-photon emission tomography/computed tomography (SPET/CT). In conclusion, the alginate-carrageenan-Brucea javanica oil system showed enhanced oil encapsulation efficiency, excellent floating and gastric retention abilities, and a favorable release behavior.