Poly-ε-caprolactone based nanoparticles for delivery of genistein in melanoma treatment

We developed poly-ε-caprolactone (PCL)-based nanoparticles containing D-α-tocopherol polyethylene glycol-1000 succinate (TPGS) or Poloxamer 407 as stabilizers to efficiently encapsulate genistein (GN). Two formulations, referred to as PNTPGS and PNPol, were prepared using nanoprecipitation. They were characterized by size and PDI distribution, zeta potential, nanoparticle tracking analysis (NTA), GN association (AE%), infrared spectroscopy (FT-IR), and differential scanning calorimetry (DSC). PNTPGS-GN exhibited a particle size of 141.2 nm, a PDI of 0.189, a zeta potential of -32.9 mV, and an AE% of 77.95%. PNPol-GN had a size of 146.3 nm, a better PDI than PNTPGS-GN (0.150), a less negative zeta potential (-21.0 mV), and an AE% of 68.73%. Thermal and spectrometric analyses indicated that no new compounds were formed, and there was no incompatibility detected in the formulations. Cellular studies revealed that Poloxamer 407 conferred less toxicity to PCL nanoparticles. However, the percentage of uptake decreased compared to the use of TPGS, which exhibited almost 80% cellular uptake. This study contributes to the investigation of stabilizers capable of conferring stability to PCL nanoparticles efficiently encapsulating GN. Thus, the PCL nanoparticle proposed here is an innovative nanomedicine for melanoma therapy and represents a strong candidate for specific pre-clinical and in vivo studie

Technology and principle of improving solubility of Dioscoreae Rhizoma formula granules based on powder modification / 中国中药杂志

The powder modification technology was used to improve the powder properties and microstructure of Dioscoreae Rhizoma extract powder, thereby solving the problem of poor solubility of Dioscoreae Rhizoma formula granules. The influence of modifier dosage and grinding time on the solubility of Dioscoreae Rhizoma extract powder was investigated with the solubility as the evaluation index, and the optimal modification process was selected. The particle size, fluidity, specific surface area, and other powder properties of Dioscoreae Rhizoma extract powder before and after modification were compared. At the same time, the changes in the microstructure before and after modification was observed by scanning electron microscope, and the modification principle was explored by combining with multi-light scatterer. The results showed that after adding lactose for powder modification, the solubility of Dioscoreae Rhizoma extract powder was significantly improved. The volume of insoluble substance in the liquid of modified Dioscoreae Rhizoma extract powder obtained by the optimal modification process was reduced from 3.8 mL to 0 mL, and the particles obtained by dry granulation of the modified powder could be completely dissolved within 2 min after being exposed to water, without affecting the content of its indicator components adenosine and allantoin. After modification, the particle size of Dioscoreae Rhizoma extract powder decreased significantly, d_(0.9) decreased from(77.55±4.57) μm to(37.91±0.42) μm, the specific surface area and porosity increased, and the hydrophilicity improved. The main mechanism of improving the solubility of Dioscoreae Rhizoma formula granules was the destruction of the "coating membrane" structure on the surface of starch granules and the dispersion of water-soluble excipients. This study introduced powder modification technology to solve the solubility problem of Dioscoreae Rhizoma formula granules, which provided data support for the improvement of product quality and technical references for the improvement of solubility of other similar varieties.

Preparation and quality evaluation of total flavonoids microemulsion of "Pueraria lobata-Hovenia dulcis" / 中国中药杂志

The effective components of flavonoids in the "Pueraria lobata-Hovenia dulcis" drug pair have low bioavailability in vivo due to their unstable characteristics. This study used microemulsions with amphoteric carrier properties to solve this problem. The study drew pseudo-ternary phase diagrams through titration compatibility experiments of the oil phase with emulsifiers and co-emulsifiers and screened the prescription composition of blank microemulsions. The study used average particle size and PDI as evaluation indicators, and the central composite design-response surface method(CCD-RSM) was used to optimize the prescription; high-dosage drug-loaded microemulsions were obtained, and their physicochemical properties, appearance, and stability were evaluated. The results showed that when ethyl butyrate was used as the oil phase, polysorbate 80(tween 80) as the surfactant, and anhydrous ethanol as the cosurfactant, the maximum microemulsion area was obtained. When the difference in results was small, K_(m )of 1∶4 was chosen to ensure the safety of the prescription. The prescription composition optimized by the CCD-RSM was ethyl butyrate(16.28%), tween 80(9.59%), and anhydrous ethanol(38.34%). When the dosage reached 3% of the system mass, the total flavonoid microemulsion prepared had a clear and transparent appearance, with average particle size, PDI, and potential of(74.25±1.58)nm, 0.277±0.043, and(-0.08±0.07) mV, respectively. The microemulsion was spherical and evenly distributed under transmission electron microscopy. The centrifugal stability and temperature stability were good, and there was no layering or demulsification phenomenon, which significantly improved the in vitro dissolution of total flavonoids.

Preparation of vitexin albumin nanoparticles and its pharmacokinetic study / 中国中药杂志

This study aims to prepare vitexin albumin nanoparticles(VT-BSA-NPs) to alleviate the low bioavailability of vitexin(VT) in vivo due to its poor water solubility. VT micro powders were prepared by the antisolvent crystallization method, and the morphology, size, and physicochemical properties of VT micro powders were studied. The results showed that the VT micro powder had a particle size of(187.13±7.15) nm, an approximate spherical morphology, and a uniform size distribution. Compared with VT, the chemical structure of VT micro powders has not changed. VT-BSA-NPs were prepared from VT micro powders by desolvation-crosslinking curing method. The preparation process was screened by single factor test and orthogonal test, and the quality evaluation of the optimal prescription particle size, PDI, Zeta potential, EE, and morphology was performed. The results showed that the average particle size of VT-BSA-NPs was(124.33±0.47) nm; the PDI was 0.184±0.012; the Zeta potential was(-48.83±2.20) mV, and the encapsulation rate was 83.43%±0.39%, all of which met the formulation-related requirements. The morphological results showed that the VT-BSA-NPs were approximately spherical in appearance, regular in shape, and without adhesion on the surface. In vitro release results showed a significantly reduced release rate of VT-BSA-NPs compared with VT, indicating a good sustained release effect. LC-MS/MS was used to establish an analytical method for in vivo analysis of VT and study the plasma pharmacokinetics of VT-BSA-NPs in rats. The results showed that the specificity of the analytical method was good, and the extraction recovery was more than 90%. Compared with VT and VT micro powders, VT-BSA-NPs could significantly increase AUC, MRT, and t_(1/2), which was beneficial to improve the bioavailability of VT.

Mechanism of Der f 1/IGF-1 nanoparticle promoting the production of regulatory T cell / 临床耳鼻咽喉头颈外科杂志

Objective:To prepare PLGA nanoparticles loaded with Der f 1/IGF-1（Der f 1/IGF-1 NPs） and investigate their role in promoting the formation of Treg cells. Methods:NPs coated with Der f 1/IGF-1 were prepared by double emulsion method and their physicochemical properties and cumulative release rate in vitro were analyzed. After pretreatment, BMDC was divided into Saline group, Blank NPs group, Der f 1/IGF-1 group and Der f 1/IGF-1 NPs group. Determination of the expression of IL-10 and TGF-β in BMDC by ELISA. The number of Treg cells was detected by flow cytometry. Results:The results showed that Der f 1/IGF-1 NPs were spherical structures, with good dispersion, particle size less than 200 nm, negative charge and stable slow-release effect of Zeta potential. After BMDC pretreatment, the expression levels of TGF-β and IL-10 in BMDC cells in the Der f 1/IGF-1 NPs group were significantly increased compared with the Blank NPs group, and the difference was statistically significant（P<0.001）. After co-culture with CD4+ T cells, the proportion of Treg cells produced in the Der f 1/IGF-1 NPs group was significantly increased, and the difference was statistically significant（P<0.001）. Conclusion:Der f 1/IGF-1 NPs can induce Treg cell generation in vitro. This study provides a new and more effective method for the reconstruction of immune tolerance dysfunction.

Research progress on the preparation and application of flavonoid nanocrystals / 浙江大学学报·医学版

Flavonoids have been reported to possess significant pharmacological activities,such as antioxidant, anti-inflammatory and anticancer effects. However, the low solubility and low bioavailability limits their clinical application. Nanocrystal technology can solve the delivery problems of flavonoids by reducing particle size, increasing the solubility of insoluble drugs and improving their bioavailability. This article summaries nanosuspension preparation methods and the stabilizers for flavonoid nanocrystals, and reviews the drug delivery routes including oral, Injection and transdermal of flavonoid nanocrystals, to provide information for further research on nanocrystal delivery system of flavonoids.

Zootechnical indices and digestibility in juveniles of tambaqui Colossoma macropomum fed a diet containing particulate maize / Índices zootécnicos e digestibilidade em juvenis de tambaqui Colossoma macropomum alimentados com dieta contendo milho particulado

Three experiments were done with different particle sizes of corn feed on its zootechnical performance, passing rate and apparent digestibility of juvenile tambaqui (Colossoma macropomum). In the first, 200 juveniles were used and distributed in 20 tanks (220 L), 10 fish per unit (four replicates). The experimental system used to record passage time was composed of five incubators with 200 L. In the second, 75 juveniles were used per 55 days (three replications). In the third, 75 juveniles were used and distributed in five incubators of 200 L. All experiments were performed randomly. Different linear behavior treatments were observed for apparent digestibility of crude protein; and the smaller particle size (150 µm) had better results digestibility. smaller particle size of the corn had better results, affected the growth performance of tambaqui and the apparent digestibility of crude protein and ether extract. Thus, is recommended that a particle size of 150 µm of corn be used for tambaqui.

Três experimentos foram realizados com diferentes tamanhos de partícula de ração para o desempenho zootécnico, taxa de aprovação e digestibilidade aparente de tambaqui juvenil (Colossoma macropomum). No primeiro, foram utilizados 200 juvenis e distribuídos em 20 tanques (220 L), 10 peixes por unidade (quatro repetições). O sistema experimental utilizado para registrar o tempo de passagem foi composto por cinco incubadoras com 200 L. No segundo, 75 juvenis foram utilizados por 55 dias (três repetições). No terceiro, 75 juvenis foram utilizados e distribuídos em cinco incubadoras de 200 L. Todos os experimentos foram realizados aleatoriamente. Diferentes tratamentos de comportamento linear foram observados para digestibilidade aparente da proteína bruta; e o menor tamanho de partícula (150 µm) apresentou melhor digestibilidade dos resultados. menor tamanho de partícula do milho apresentou melhores resultados, afetou o desempenho de crescimento de tambaquis e a digestibilidade aparente da proteína bruta e extrato etéreo. Portanto, recomenda-se o uso de um tamanho de partícula de 150 µm de milho para o tambaqui.

Optimization of formulation of paclitaxel nanosuspension encapsulated by erythrocyte membrane based on Box-Behnken method / 中国中药杂志

In view of the longevity and innate immune escape of red blood cells, this study designed the red blood cell membrane-coated paclitaxel nanosuspension [RBC-(PTX)NS] and investigated its physicochemical properties and antitumor effect in vitro. Paclitaxel nanosuspension [(PTX)NS] was prepared by ultrasonic precipitation and then RBC-(PTX)NS by ultrasonic coating. The formulation of(PTX)NS was optimized with Box-Behnken method and indexes of particle diameter, zeta potential, and stability. The morphology, particle diameter, stability, in vitro dissolution, and antitumor effect of(PTX)NS and RBC-(PTX)NS were characterized. The results showed that the particle diameter and zeta potential were(129.38±0.92) nm and(-22.41±0.48) mV, respectively, for the optimized(PTX)NS, while(142.5±0.68) nm and(-29.85±0.53) mV, respectively, for RBC-(PTX)NS. Under the transmission electron microscope,(PTX)NS was spherical and RBC-(PTX)NS had obvious core-shell structure. RBC-(PTX)NS remained stable for 5 days at 4 ℃. The in vitro dissolution test demonstrated that the cumulative release rate of RBC-(PTX)NS reached 79% within 20 min, which was significantly higher than that(25%) of(PTX)NS(P<0.05). As evidenced by MTT assay, RBC-(PTX)NS highly inhibited the proliferation of HepG2 cells in a dose-dependent manner. The cell membrane-coated nano-preparation preparation method is simple and reproducible. It improves the solubility of PTX and endows RBC-(PTX)NS with higher stability and stronger cytotoxicity. Thus, it is a new method for the delivery of PTX via nanocrystallization.

Preparation of tanshinone Ⅱ_A-glycyrrhetinic acid solid lipid nanoparticles and its inhibitory effect on acne / 中国中药杂志

The optimal prescription of tanshinone Ⅱ_A(TSN)-glycyrrhetinic acid(GA) solid lipid nanoparticles(GT-SLNs) was explored and evaluated in vivo and in vitro, and its effect on acne after oral administration was investigated. The preparation processing and prescription were optimized and verified by single factor and response surface methodology. The in vitro release of GA and TSN in GT-SLNs was determined by ultra-performance liquid chromatography(UPLC). The effect of GT-SLNs on acne was investigated by the levels of sex hormones in mice, ear swelling model, and tissue changes in sebaceous glands, and the pharmacokinetics was evaluated. The 24-hour cumulative release rates of GA and TSN in SLNs were 65.87%±5.63% and 36.13%±2.31% respectively. After oral administration of GT-SLNs and the mixture of GA and TSN(GT-Mix), the AUC_(0-t) and AUC_(0-∞) of TSN in GT-SLNs were 1.98 times and 4.77 times those in the GT-Mix group, respectively, and the peak concentration of TSN in the GT-SLNs group was 17.2 times that in the GT-Mix group. After intragastric administration of GT-SLNs, the serum levels of testosterone(T) and the ratio of testosterone to estradiol(T/E2) in the GT-SLNs group significantly declined, and the sebaceous glands of mice were atrophied to a certain extent. The results demonstrated that obtained GT-SLNs with good encapsulation efficiency and uniform particle size could promote the release of GA and TSN. GT-SLNs displayed therapeutic efficacy on acne manifested by androgen increase, abnormal sebaceous gland secretion, and inflammatory damage.

Preparation and in vitro release of quercetin nanocrystals self-stabilized Pickering emulsion / 中国中药杂志

A new quercetin nanocrystals self-stabilized Pickering emulsion(QT-NSSPE) was prepared by high-pressure homogenization combined with probe ultrasonic method. The influences of oil fraction, quercetin(QT) concentration, and pH of water phase on the formation of QT-NSSPE were investigated. On this basis, the QT-NSSPE prepared under optimal conditions was evaluated in terms of microstructure, stability, and in vitro release and the droplet size and drug loading were 15.82 μm and 4.87 mg·mL~(-1), respectively. The shell structure formed by quercetin nanocrystals(QT-NC) on the emulsion droplet surface was observed under a scanning electron microscope(SEM). X-ray diffraction(XRD) showed that the crystallinity of adsorbed QT-NC decreased significantly as compared with the raw QT. There were not significant changes of QT-NSSPE properties after 30 days of storage at room temperature. The in vitro release experiment confirmed that QT-NSSPE has a higher accumulative release rate than the raw QT. All these results indicated that QT-NSSPE has a great stability and a satisfactory in vitro release behavior, which is a promising new oral delivery system for QT.

Soybean meal particle size for pigs during the nursery phase / Tamanho da partícula do farelo de soja em suínos no período de creche

This study evaluated the effect of soybean meal (SBM) particle size on nutrient digestibility and the growth performance of nursery piglets. Sixty-three piglets (BW = 6.86 kg ± 0.56; 23 d of age) were distributed in a randomized block design (by initial weight and sex) with 3 dietary treatments: diets with 1,017 µm (unground); 585 µm; and 411µm SBM, with 7 replicates of 3 piglets each. All diets were offered ad libitum in mash form, formulated differently according to three growing phases: (1) with 20% of SBM, from 23 to 32 d of age; (2) with 25% of SBM, from 32 to 44 d of age, and (3) with 30% of SBM, from 44 to 63 d of age. For the first 21 d, pigs fed diets with a medium particle size of SBM (585mm) had better average weight gain and feed/gain ratio (P<0.05). The average feed intake, average body weight gain, and feed/gain ratio from 44 to 63 d improved (P<0.05) with increasing SBM particle sizes, and the average live weight for the overall period increased with coarser SBM (P<0.05). There was a marginally improvement (P < 0.1) on digestible energy as particle size of SBM decreased; although, no differences (P > 0.05) in the coefficients of apparent digestibility of dry matter and crude protein for the assessed SBM particle sizes were observed. It was concluded that the grinding of dietary SBM is not required for piglets during the nursery phase.

O objetivo deste estudo foi avaliar o efeito do tamanho da partícula do farelo de soja (FS) sobre o desempenho e digestibilidade de leitões no período de creche. 63 leitões (6,86 kg ± 0,56; 23 dias de idade) foram distribuídos aleatoriamente em um delineamento de blocos casualizados (peso inicial e sexo) entre os tratamentos. As dietas experimentais foram produzidas a partir de diferentes tamanhos médios de partículas do FS moídos ou não: 1,017 µm (sem moer), 585 µm (moído em peneira de 10 mm), e 411µm (moído em peneira de 3 mm), totalizando três tratamentos com sete repetições de três animais cada. Todas as dietas foram fornecidas na forma farelada e ad libitum, sendo divididas em três fases: 1) com 20% de FS, dos 23 a 32 dias de idade; 2) com 25% de FS, dos 32 a 44 dias de idade; e 3) com 30% de FS, dos 44 a 62 dias de idade. Nos primeiros 21 dias de experimento, os animais consumindo a dieta com o tamanho médio (585 µm) das partículas do FS apresentaram melhores resultados para o ganho de peso médio e conversão alimentar. No período seguinte (44 a 63 d), houve (P<0.05) aumento do consumo de ração médio, do ganho do peso médio e melhor conversão alimentar dos leitões conforme o aumento do tamanho da partícula de FS incluída na ração. Consequentemente, ao final do experimento houve melhora linear do peso vivo médio dos animais com o aumento do tamanho do FS consumido. Foi observado melhora marginalmente significativa (P < 0.1) da energia digestível conforme a redução no tamanho do FS, entretanto, não houve diferença (P > 0.05) no coeficiente de digestibilidade aparente da matéria seca e da proteína bruta dos animais entre os diferentes tamanhos do FS. Em conclusão, de acordo com as condições deste estudo, não se faz necessária a moagem do farelo de soja para leitões no período de creche.

Particle size of oyster shell meal and calcium: phosphorus ratios in broiler diets / Efeito do tamanho de partícula da farinha de ostras e relações cálcio: fósforo em dietas para frangos de corte

The effects of Ca:P total ratio and particle size of oyster shell meal (OSM) were evaluated in broiler diets. In Experiment 1, 800 broilers (22-42 days old) were distributed in a 2×2 factorial design, with two Ca:P ratios (1.7 and 2.0:1) and two OSM particle sizes (coarse = 1,354 µm and fine = 428 µm), totaling four treatments with 10 repetitions with 20 broilers. Feed intake, weight gain, and feed conversion ratio were calculated. In Experiment 2, 1,280 broilers were distributed in a 2×2×2 factorial design (1.7 and 2.0:1 Ca:P ratios; coarse and fine OSM; male and female broilers), with eight treatments and 16 repetitions with 10 broilers. Apparent metabolizability of dry matter, Ca, P, and apparent metabolizable energy (AME), as well as bone resistance, bone weight, ash, Ca, and P content in the tibia were assessed. Growth performance was not affected (P > 0.05). Coarse OSM increased tibia Ca content in male broilers (P < 0.001), and higher Ca:P ratio improved bone ash and bone resistance in both sexes (P < 0.001), but reduced P content in male broilers (P < 0.05); male broilers displayed heavier bones with higher ash content than females (P < 0.05). Metabolizability of Ca was improved with coarse OSM (P < 0.05); whereas metabolizability of DM, P, and AME was not affected (P > 0.05). In conclusion, diets with a Ca:P total ratio of 2.0:1 containing coarser OSM improved bone mineral composition, particularly in male broilers, and coarse OSM improved the metabolizability of Ca in broilers regardless of the Ca:P total ratio or broiler sex.

Dois experimentos foram conduzidos para avaliar os efeitos do tamanho de partícula da farinha de ostras (FO) e relação Ca:P total em dietas para frangos de corte. No primeiro experimento, 800 frangos (22 a 42 dias) foram distribuídos em um delineamento fatorial 2x2: 2 relações Ca:P (1,7 e 2,0:1) e dois tamanhos de partícula da FO (grossa = 1354 µm e fina = 428 µm), totalizando quatro tratamentos com 10 repetições de 20 aves. O consumo de ração, o ganho de peso e a conversão alimentar foram calculados. No segundo experimento, 1.280 frangos foram distribuídos em um fatorial 2x2x2 (relações Ca:P 1,7 e 2,0:1; FO grossa e fina; aves machos e fêmeas) com oito tratamentos e 16 repetições de 10 aves. Foram avaliados: metabolizabilidade aparente da matéria seca, Ca e P, energia metabolizável aparente (EMA), peso e resistência óssea, conteúdo de cinzas, Ca e P na tíbia. As variáveis de desempenho não foram afetadas (P > 0,05). O uso de FO grossa aumentou o conteúdo de Ca na tíbia de frangos machos (P < 0,001), e a relação Ca:P de 2,0:1 aumentou o conteúdo de cinzas e aprimorou resistência óssea em ambos os sexos (P < 0,001), porém reduziu P na tíbia dos machos (P < 0,05); frangos machos também tiveram ossos mais pesados e maior conteúdo de cinzas do que fêmeas (P < 0,05). A metabolizabilidade de Ca foi melhorada com FO grossa, enquanto a metabolizabilidade da matéria seca, P, e EMA não foram afetadas (P > 0,05). Conclui-se que as dietas com relação Ca:P de 2,0:1 e com FO grossa resultaram em melhor composição mineral óssea - particularmente em frangos machos - e a FO grossa melhorou a metabolizabilidade de Ca independentemente da relação Ca:P ou do gênero das aves.

Efavirenz dissolution enhancement V - A combined top down/bottom up approach on nanocrystals formulation

Abstract Efavirenz is one of the most commonly used drugs in HIV therapy. However the low water solubility tends to result in low bioavailability. Drug nanocrystals, should enhance the dissolution and consequently bioavailability. The aim of the present study was to obtain EFV nanocrystals prepared by an antisolvent technique and to further observe possible effect, on the resulting material, due to altering crystallization parameters. A solution containing EFV and a suitable solvent was added to an aqueous solution of particle stabilizers, under high shear agitation. Experimental conditions such as solvent/antisolvent ratio; drug load; solvent supersaturation; change of stabilizer; addition of milling step and solvents of different polarities were evaluated. Suspensions were characterized by particle size and zeta potential. After freeze- dried and the resulting powder was characterized by PXRD, infrared spectroscopy and SEM. Also dissolution profiles were obtained. Many alterations were not effective for enhancing EFV dissolution; some changes did not even produced nanosuspensions while other generated a different solid phase from the polymorph of raw material. Nevertheless reducing EFV load produced enhancement on dissolution profile. The most important modification was adding a milling step after precipitation. The resulting suspension was more uniform and the powder presented grater enhancement of dissolution efficacy.

The influence of the particle's size on the setting reaction of sol-gel derived calcium silicate particles / A influência do tamanho de partícula na reação de presa de cimentos de silicate de cálcio produzidos por sol-gel

Introduction: This study aims to analyze the influence of particles size of sol-gel derived calcium silicate particles in the setting reaction of bioactive endodontic cements. Materials and Methods: Sol-gel derived calcium silicate particles were synthesized and sieved to separate the particles in different sizes: CS400, CS200, and CS100. A commercial MTA (Control) was used as control. The particle size and the specific surface area were assessed by laser diffraction and nitrogen adsorption. The cements were prepared with water as the liquid for the reaction. The setting time was conducted according to ISO 6876, and the setting kinetics was analyzed by Fourier trans-formed infrared spectroscopy (FTIR) at different time points between 120s to 72h. Results: The particle size varied from 9.45µm (CS400 ) to 31.01 (Control). The higher specific surface area valuer reached 15.14g/cm2 in the CS400. The smallest particle sizes, the higher specific surface area, and the lowest setting time were found for CS400 (p < 0.05). Control presented the highest setting time (p < 0.05). The FTIR analyses showed the differences in materials structure over time, with faster hydration and crystallization for CS400. The setting kinetics was slower for Control even when compared to a sol-gel derived group with similar particle size. Conclusion:The route of synthesis and the particle size influences the setting reaction of calcium silicate-based cements. The reduction of particle size for sol-gel derived calcium silicates lead to the acceleration of the setting reaction of the produced bioactive endodontic cement.

Introdução: Este estudo tem como objetivo analisar a influência do tamanho de partículas de silicato de cálcio derivadas de sol-gel na reação de presa de cimentos endodônticos bioativos. Materiais e Métodos: Partículas de silicato de cálcio derivadas de sol-gel foram sintetizadas e peneiradas para separar as partículas em diferentes tamanhos: CS400, CS200 e CS100. Um MTA comercial (Controle) foi usado como controle. O tamanho das partículas e a área superficial específica foram avaliados por difração a laser e adsorção de nitrogênio. Os cimentos foram preparados com água como líquido para a reação. O tempo de presa foi conduzido de acordo com a ISO 6876, e a cinética de presa foi analisada por espectroscopia de infravermelho transformada de Fourier (FTIR) em diferentes pontos de tempo entre 120s a 72h. Resultados: O tamanho de partícula variou entre 9,45µm (CS400) e 31,01 (Controle). A maior área de superfície foi encontrada nas partículas do grupo CS400 (15.14g/cm2). Os menores tamanhos de partícula, a maior área de superfície específica e o menor tempo de presa foram encontrados para CS400 (p < 0,05). O Control apresentou o maior tempo de presa (p < 0,05). As análises de FTIR mostraram as diferenças na estrutura dos materiais ao longo do tempo, com hidratação e cristalização mais rápidas para CS400. A cinética de presa foi mais lenta para Control mesmo quando comparado a um grupo derivado de sol-gel com tamanho de partícula semelhante. Conclusão: A rota de síntese e o tamanho das partículas influenciam a reação de endurecimento dos cimentos à base de silicato de cálcio. A redução do tamanho de partícula para silicatos de cálcio derivados de sol-gel leva à aceleração da reação de pega do cimento endodôntico bioativo produzido.

Air pollution and children's health-a review of adverse effects associated with prenatal exposure from fine to ultrafine particulate matter

BACKGROUND@#Particulate matter (PM), a major component of ambient air pollution, accounts for a substantial burden of diseases and fatality worldwide. Maternal exposure to PM during pregnancy is particularly harmful to children's health since this is a phase of rapid human growth and development.@*METHOD@#In this review, we synthesize the scientific evidence on adverse health outcomes in children following prenatal exposure to the smallest toxic components, fine (PM@*RESULTS@#Maternal exposure to fine and ultrafine PM directly and indirectly yields numerous adverse birth outcomes and impacts on children's respiratory systems, immune status, brain development, and cardiometabolic health. The biological mechanisms underlying adverse effects include direct placental translocation of ultrafine particles, placental and systemic maternal oxidative stress and inflammation elicited by both fine and ultrafine PM, epigenetic changes, and potential endocrine effects that influence long-term health.@*CONCLUSION@#Policies to reduce maternal exposure and health consequences in children should be a high priority. PM

Puerarin-Chuanxiong oil submicron emulsion combining medicine and adjuvant / 中国中药杂志

This study was mainly based on the compatibility of Puerariae Lobatae Radix and Chuanxiong Rhizoma to prepare submicron emulsion and evaluated its physical and pharmaceutical properties. Firstly, pseudo-ternary phase diagrams were drawn by dripping method which took Chuanxiong oil as the oil phase and the area of microemulsion region as the index. On this basis, suitable emulsifier and co-emulsifier were screened for the preparation of Chuanxiong oil submicron emulsion. Then, the formula realizing the largest oil loading was selected. Finally, puerarin substituted part of emulsifier and co-emulsifier to lower their content, so as to form puerarin-Chuanxiong oil submicron emulsion featuring the combination of medicine and adjuvant. Its particle size, zeta potential, centrifugal stability and storage stability were determined, and the in vitro drug release behavior was investigated by dialysis bag method, based on which the quality of the as-prepared submicron emulsion was evaluated comprehensively. The proposed method was proved feasible for the preparation of Chuanxiong oil submicron emulsion, which adopted polyoxyethylene castor oil(EL-40) as the emulsifier and was free from co-emulsifier. The formula of the maximum oil loading was found as Chuanxiong oil∶EL-40∶water 3∶7∶90. Further, puera-rin successfully replaced up to 10% of the emulsifier in submicron emulsion. Eventually, the optimal drug-loading formula was determined as puerarin∶Chuanxiong oil∶EL-40∶water 7∶30∶63∶900. The quality evaluation results of the as-prepared submicron emulsion demonstrated that the average emulsion droplet size was 333.9 nm, the PDI 0.26, and the zeta potential-10.12 mV. The submicron emulsion had a good centrifugal stability and did not present any instable phenomena such as delamination and precipitation during its standing still for 50 days. The evaluation of in vitro drug release behavior indicated that the submicron emulsion was capable of releasing the drug completely. The puerarin-chuanxiong oil submicron emulsion prepared in this study possessed a stable quality and to some extent increased the solubility of puerarin along with a sustained-release effect. This study provided ideas for the clinical application of puerarin.

Preparation of paclitaxel-loaded and folic acid-modified poly (lactic-co-glycolic acid) nano-micelles and in vitro anticancer effect on cervical cancer HeLa cells / 中国中药杂志

The paclitaxel-loaded and folic acid-modified poly(lactic-co-glycolic acid) nano-micelles(PTX@FA-PLGA-NMs) were prepared by the emulsion solvent evaporation method, and the parameters of paclitaxel-loaded nano-micelles were optimized with the particle size and PDI as evaluation indexes. The morphology of the nano-micelles was observed by transmission electron microscopy(TEM), and the stability, drug loading and encapsulation efficiency were systematically investigated. In vitro experiments were performed to study the cytotoxic effects of nano-micelles, apoptosis, and cellular uptake. Under the optimal parameters, the nano-micelles showed the particle size of(125.3±1.2) nm, the PDI of 0.086±0.026, the zeta potential of(-20.0±3.8) mV, the drug loading of 7.2%±0.75%, and the encapsulation efficiency of 50.7%±1.0%. The nano-micelles were in regular spherical shape as observed by TEM. The blank FA-PLGA-NMs exhibited almost no inhibitory effect on the proliferation and growth of tumor cells, while the drug-loaded nano-micelles and free PTX exhibited significant inhibitory effects. The IC_(50) of PTX@FA-PLGA-NMs and PTX was 0.56 μg·mL~(-1) and 0.66 μg·mL~(-1), respectively. The paclitaxel-loaded nano-micelles were potent in inhibiting cell migration as assessed by the scratch assay. PTX@FA-PLGA-NMs had good pro-apoptotic effect on cervical cancer HeLa cells and significantly promoted the uptake of HeLa cells. The results of in vitro experiments suggested that PTX@FA-PLGA-NMs could target and treat cervical cancer HeLa cells. Therefore, as nanodrug carriers, PTX@FA-PLGA-NMs with anti-cancer activity are a promising nano-system for improving the-rapeutic effects on tumors.

Effects of HPMCAS MF on absorption of silybin from supersaturable self-nanoemulsifying drug delivery system / 中国中药杂志

To evaluate the effects of Hydroxypropyl methylcellulose acetate succinate(HPMCAS MF) on absorption of silybin(SLB) from supersaturable self-nanoemulsifying drug delivery system which was pre-prepared at the early stage experiment. The cell toxicity of self-emulsifying preparation was evaluated by the MTT method, and the in vitro membrane permeability and absorption promoting effect of the self-emulsifying preparation were evaluated by establishing a Caco-2 cell monolayer model. The in vivo and in vitro supersaturation correlation was evaluated via the blood concentration of SLB. The results of MTT showed that the concentration of the preparation below 2 mg·mL~(-1)(C_(SLB) 100 μg·mL~(-1)) was not toxic to Caco-2 cells, and the addition of polymer had no significant effect on Caco-2 cells viability. As compared with the solution group, the transport results showed that the P_(app)(AP→BL) of the self-emulsifying preparation had a very significant increase; the transport rate of silybin can be reduced by polymer in 0-30 min; however, there was no difference in supersaturated transport between supersaturated SLB self-nanoemulsion drug delivery system(SLB-SSNEDDS) and SLB self-nanoemulsion drug delivery system(SLB-SNEDDS) within 2 hours. As compared with SLB suspension, pharmacokinetic parameters showed that the blood concentration of both SLB-SNEDDS and SLB-SSNEDDS groups were significantly increased, and C_(max) was 5.25 times and 9.69 times respectively of that in SLB suspension group, with a relative bioavailability of 578.45% and 1 139.44% respectively. C_(max) and relative bioavailability of SLB-SSNEDDS were 1.85 times and 197% of those of SLB-SNEDDS, respectively. Therefore, on the one hand, SSNEDDS can increase the solubility of SLB in gastrointestinal tract by maintaining stability of SLB supersaturation state; on the other hand, the osmotic transport process of SLB was regulated through the composition of its preparations, and both of them could jointly promote the transport and absorption of SLB to improve the oral bioavailability of SLB.

Powder modificationfor improving content uniformity of Ziyin Yiwei Capsules / 中国中药杂志

Based on the defects in powder properties of the contents of Ziyin Yiwei Capsules, this study screened out the main medicinal slice powders causing the poor powdery properties, and introduced the powder modification process to improve the powdery properties of these slice powders, the pharmaceutical properties of the capsule contents, and the content uniformity of Ziyin Yiwei Capsules, so as to provide a demonstration for the application of powder modification technology to the preparation of Chinese medicinal solid preparations. Through the investigation on the powder properties of the contents of Ziyin Yiwei Capsules, it was clarified that the pulverized particle size of the capsule contents had a good correlation with the pulverization time. According to the measurement results of the powder fluidity and wettability, the quality defects of the capsule contents were caused by the fine powders of Taraxaci Herba and Lungwortlike Herba. "Core-shell" composite particles were prepared from medicinal excipients magnesium stearate and fine powders of Taraxaci Herba and Lungwortlike Herba slices after ultra-fine pulverization to improve the powder properties of the problematic fine powders. Powder characterization data including fluidity and wettability were measured, followed by scanning electron microscopy(SEM) and infrared ray(IR) detection. It was determined that the optimal dosage of magnesium stearate was 2%, and the compositing time was 3 min. The composite particles were then used as content components of the Ziyin Yiwei Capsules. The powder characteristics between the original capsule and the modified composite capsule including the particle size, fluidity, wettability, uniformity of bulk density, and uniformity of chromatism as well as the content uniformity and in vitro dissolution were compared. The results showed that the powder characteristics and content uniformity of the prepared composite capsule were significantly improved, while the material basis of the preparation was not changed before and after modification. The preparation process was proved to be stable and feasible. The powder modification technology solved the pharmaceutical defects that were easy to appear in the preparation of traditional capsules, which has provided experimental evidence for the use of powder modification technology for improving the quality of Chinese medicinal solid preparations and promoting the secondary development and upgrading of traditional Chinese medicinal dosage forms such as capsules.

Particle design for improving content uniformity of Hewei Jiangni Capsules / 中国中药杂志

Targeting the poor powder characteristics of the contents in Hewei Jiangni Capsules, this study characterized the powder properties of the contents and employed particle design technique for improving the content quality. The content composite particles of Hewei Jiangni Capsules prepared by the particle design technique were evaluated by scanning electron microscopy(SEM), followed by infrared ray(IR), content uniformity, and in vitro dissolution detection. It was found that there was a good correlation between the crushed particle size of slices and the crushing time, and the calcined Haematitum was responsible for the poor content uniformity. After the fine powder of calcined Haematitum was super-finely ground for 8.5 min and those of the other contents in the capsule for 1 min, they were prepared into the composite particles, whose property characterizations were compared with those of the physical mixtures. The content uniformity of the prepared composite particles was significantly improved, and the preparation process was stable and reliable. The adoption of particle design technology to correct the poor uniformity of the physical mixture, solve the pharmaceutical defects of Hewei Jiangni Capsules, and improve the quality of prescriptions has provided important reference for the clinical application and development of Chinese medicinal preparations.