PLGA-modified Syloid®-based microparticles for the ocular delivery of terconazole: in-vitro and in-vivo investigations

The eye is an invulnerable organ with intrinsic anatomical and physiological barriers, hindering the development of a pioneer ocular formulation. The aim of this work was to develop an efficient ocular delivery system that can augment the ocular bioavailability of the antifungal drug, terconazole. Mesoporous silica microparticles, Syloid^® 244 FP were utilized as the carrier system for terconazole. Preliminary studies were carried out using different drug:Syloid^® weight ratios. The optimum weight ratio was mixed with various concentrations (30 and 60%w/w) of poly (lactic-co-glycolic acid) (PLGA), ester or acid-capped and with different monomers-ratio (50:50 and 75:25) using the nano-spray dryer. Results revealed the superiority of drug:Syloid^® weight ratio of 1:2 in terms of yield percentage (Y%), SPAN and drug content percentage (DC%). Furthermore, incorporation of PLGA with lower glycolic acid monomer-ratio significantly increased Y%. In contrast, increasing the glycolic acid monomer-ratio resulted in higher DC% and release efficiency percentage (RE%). Additionally, doubling PLGA concentration significantly reduced Y%, DC%, drug loading percentage (DL%) and RE%. Applying desirability function in terms of increasing DC%, DL% besides RE% and decreasing SPAN, the selected formulation was chosen for DSC, XRD and SEM investigations. Results confirmed the successful loading of amorphized terconazole on PLGA-modified Syloid^® microparticles. Moreover, pharmacokinetic studies for the chosen formulation on male Albino rabbits’ eyes revealed a 2, 6.7 and 25.3-fold increase in mean residence time, C_max and AUC_0–24-values, respectively, compared to the drug suspension. PLGA-modified Syloid^® microparticles represent a potential option to augment the bioavailability of ocular drugs.     

基于氧化亚铜纳米颗粒的光热/化学动力协同策略体外抑制胃癌细胞的迁移

目的 探讨氧化亚铜(Cu₂O)纳米的制备、物化表征及其胃癌抗肿瘤效应的作用。方法 采用透射电镜,动态光散射,Zeta电位分析及紫外吸收光谱分析方法分析Cu₂O纳米的形貌、粒径大小及类芬顿性能,利用不同浓度的Cu₂O纳米对细胞进行处理,并进行光照或者非光照处理,并分别采用细胞增殖-毒性实验(CCK-8)、Transwell细胞迁移实验评估该纳米的体外抗肿瘤作用效应。结果 制备的Cu₂O纳米为100 nm左右的类圆形结构,在近红外光(NIR, 0.5/cm2)照射5 min后Cu₂O纳米温度从25℃提高到50℃,同时Cu₂O纳米在过氧化氢浓度和pH为近中性的条件下(pH=6.5)可催化大量活性氧(ROS)生成。CCK-8试验表明：相比于对照组,Cu₂O纳米对胃癌细胞具有浓度依赖性抑制增殖作用;Transwell细胞迁移实验表明：Cu₂O纳米能抑制胃癌细胞的迁移能力。结论 Cu₂O铜基纳米颗粒具备...     

Enhanced Nitrate Ions Remediation Using Fe0 Nanoparticles from Underground Water: Synthesis,Characterizations, and Performance under Optimizing Conditions

The presence of nitrates in water in large amounts is one of the most dangerous health issues. The greatest risk posed by nitrates is hemoglobin oxidation, which results in Methemoglobin in the human body, resulting in Methemoglobinemia. There are many ways to eliminate nitrates from underground water. One of the most effective and selective methods is using zero-valent iron (ZVI) nanoparticles. ZVI nanoparticles can be easily synthesized by reducing ferric or ferrous ions using sodium borohydride. The prepared ZVI nanoparticles were examined by scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), electron microscopy (TEM), X-ray diffraction (XRD), Brunauer–Emmett–Teller (BET) surface area, and zeta potential. We aim to eliminate or reduce the nitrates in water to be at the acceptable range, according to the world health organization (WHO), of 10.0 mg/L. Nitrate concentration in water after and before treatment is measured using the UV scanning method at 220 nm wavelength for the synthetic contaminated water and electrochemical method for the naturally contaminated water. The conditions were optimized for obtaining an efficient removing process. The removal efficiency reaches about 91% at the optimized conditions.     

Cell membrane-camouflaged PLGA biomimetic system for diverse biomedical application

The emerging cell membrane (CM)-camouflaged poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) (CM@PLGA NPs) have witnessed tremendous developments since coming to the limelight. Donning a novel membrane coat on traditional PLGA carriers enables combining the strengths of PLGA with cell-like behavior, including inherently interacting with the surrounding environment. Thereby, the in vivo defects of PLGA (such as drug leakage and poor specific distribution) can be overcome, its therapeutic potential can be amplified, and additional novel functions beyond drug delivery can be conferred. To elucidate the development and promote the clinical transformation of CM@PLGA NPs, the commonly used anucleate and eukaryotic CMs have been described first. Then, CM engineering strategies, such as genetic and nongenetic engineering methods and hybrid membrane technology, have been discussed. The reviewed CM engineering technologies are expected to enrich the functions of CM@PLGA for diverse therapeutic purposes. Third, this article highlights the therapeutic and diagnostic applications and action mechanisms of PLGA biomimetic systems for cancer, cardiovascular diseases, virus infection, and eye diseases. Finally, future expectations and challenges are spotlighted in the concept of translational medicine.     

苦参总生物碱固体脂质纳米粒的制备工艺研究

目的 探索苦参总生物碱(TA)磷脂复合物固体脂质纳米粒(TA-PC-SLN)的制备工艺及处方优化,并对其进行体外评价.方法 建立高效液相色谱(HPLC)法同时测定TA中4个指标成分苦参碱(MT)、氧化苦参碱(OMT)、槐果碱(SC)、氧化槐果碱(OSC),并进行方法学验证.称取TA、卵磷脂共同溶于乙醇制备磷脂复合物;采...     

Control of Porous Layer Thickness in Thermophoretic Deposition of Nanoparticles

The film thickness plays an important role in the performance of materials applicable to different technologies including chemical sensors, catalysis and/or energy materials. The relationship between the surface and volume of the functional layers is key to high performance evaluations. Here we demonstrate the thermophoretic deposition of different thicknesses of the functional layers designed using flame combustion of tin 2-ethylhexanoate dissolved in xylene, and measurement of thickness by scanning electron microscopy and focused ion beam. The parameters such as spray fluid concentration (differing Sn²⁺ content), substrate-nozzle distance and time of the spray were considered to investigate the layer growth. The results showed ≈ 23, 124 and 161 μm thickness of the SnO₂ layer after flame spray of 0.1, 0.5 M and 1.0 M tin 2-EHA-Xylene solutions for 1200 s. While Sn²⁺ concentration was 0.5 M for all the flame sprays, the substrates placed at 250, 220 and 200 mm from the flame nozzle had layer thicknesses of 113, 116 and 132 µm, respectively. Spray time dependent thickness growth showed a linear increase from 8.5 to 152.1 µm when the substrates were flame sprayed for 30 s to 1200 s using 0.5 M tin 2-EHA-Xylene solutions. Changing the dispersion oxygen flow (3–7 L/min) had almost no effect on layer thickness. Layers fabricated were compared to a model found in literature, which seems to describe the thickness well in the domain of varied parameters. It turned out that primary particle size deposited on the substrate can be tuned without altering the layer thickness and with little effect on porosity. Applications depending on porosity, such as catalysis or gas sensing, can benefit from tuning the layer thickness and primary particle size.     

Hardening of Additive Manufactured 316L Stainless Steel by Using Bimodal Powder Containing Nanoscale Fraction

The particle size distribution significantly affects the material properties of the additively manufactured parts. In this work, the influence of bimodal powder containing nano- and micro-scale particles on microstructure and materials properties is studied. Moreover, to study the effect of the protective atmosphere, the test samples were additively manufactured from 316L stainless steel powder in argon and nitrogen. The samples fabricated from the bimodal powder demonstrate a finer subgrain structure, regardless of protective atmospheres and an increase in the Vickers microhardness, which is in accordance with the Hall-Petch relation. The porosity analysis revealed the deterioration in the quality of as-built parts due to the poor powder flowability. The surface roughness of fabricated samples was the same regardless of the powder feedstock materials used and protective atmospheres. The results suggest that the improvement of mechanical properties is achieved by adding a nano-dispersed fraction, which dramatically increases the total surface area, thereby contributing to the nitrogen absorption by the material.     

Collagen-Carboxymethylcellulose Biocomposite Wound-Dressings with Antimicrobial Activity

Microbial infections associated with skin diseases are frequently investigated since they impact on the progress of pathology and healing. The present work proposes the development of freeze-dried, glutaraldehyde cross-linked, and non-cross-linked biocomposite dressings with a porous structure, which may assist the reepithelization process through the presence of collagen and carboxymethylcellulose, along with a therapeutic antimicrobial effect, due to silver nanoparticles (AgNPs) addition. Phisyco-chemical characterization revealed the porous morphology of the obtained freeze-dried composites, the presence of high crystalline silver nanoparticles with truncated triangular and polyhedral morphologies, as well as the characteristic absorption bands of collagen, silver, and carboxymethylcellulose. In vitro tests also assessed the stability, functionality, and the degradability rate of the obtained wound-dressings. Antimicrobial assay performed on Gram-negative (Escherichia coli), Gram-positive (Staphyloccocus aureus) bacteria, and yeast (Candida albicans) models demonstrated that composite wound dressings based on collagen, carboxymethylcellulose, and AgNPs are suitable for skin lesions because they prevent the risk of infection and have prospective wound healing capacity. Moreover, the cell toxicity studies proved that the obtained materials can be used in long time treatments, with no cytotoxic effects.     

Utilizing Edible Agar as a Carrier for Dual Functional Doxorubicin-Fe3O4 Nanotherapy Drugs

The purpose of this study was to use agar as a multifunctional encapsulating material to allow drug and ferromagnetism to be jointly delivered in one nanoparticle. We successfully encapsulated both Fe₃O₄ and doxorubicin (DOX) with agar as the drug carrier to obtain DOX-Fe₃O₄@agar. The iron oxide nanoparticles encapsulated in the carrier maintained good saturation of magnetization (41.9 emu/g) and had superparamagnetism. The heating capacity test showed that the specific absorption rate (SAR) value was 18.9 ± 0.5 W/g, indicating that the ferromagnetic nanoparticles encapsulated in the gel still maintained good heating capacity. Moreover, the magnetocaloric temperature could reach 43 °C in a short period of five minutes. In addition, DOX-Fe₃O₄@agar reached a maximum release rate of 85% ± 3% in 56 min under a neutral pH 7.0 to simulate the intestinal environment. We found using fluorescent microscopy that DOX entered HT-29 human colon cancer cells and reduced cell viability by 66%. When hyperthermia was induced with an auxiliary external magnetic field, cancer cells could be further killed, with a viability of only 15.4%. These results show that agar is an efficient multiple-drug carrier, and allows controlled drug release. Thus, this synergic treatment has potential application value for biopharmaceutical carrier materials.     

Zero-Valent Iron Nanoparticles Remediate Nickel-Contaminated Aqueous Solutions and Biosolids-Amended Agricultural Soil

Nickel (Ni⁺²) accumulation in wastewater treatment sludge poses a potential environmental risk with biosolids-land application. An incubation experiment was conducted to evaluate the effect of nanoparticles of zero-valent iron (nZVI) on Ni⁺² sorption in biosolids-treated agricultural soils. Two application rates of biosolids (0, 5%, w/w) and four treatment levels (0, 1, 5, and 10 g/kg) of nZVI were examined, either separately or interactively. The results of this study showed significant differences in Ni⁺² sorption capacity between different nZVI treatments. The initial Ni⁺² concentration in biosolids-amended soil significantly affected Ni sorption in the soil treated with nZVI. The “H-shape” of sorption isotherm in nZVI-treated soil reflects strong interaction between the Ni concentration and the nZVI treatment, while the C-shape of sorption isotherm in biosolids-amended soil without the nZVI treatment indicates intermediate affinity for Ni⁺² sorption. Nickel retention in soil was increased with the increase of nZVI levels. The removal efficiency of Ni⁺² by nZVI from solution was increased with the increase of pH from 5 to 11 and reached a maximum of 99.56% at pH 11 and nZVI treatment of 10 g/kg. The Ni⁺² desorption rate decreased from 92 to 7, 4, and 1% with increasing nZVI treatment levels from 0 to 1, 5, and 10 g/kg, respectively, with a soil Ni⁺² concentration of 50 mg/L. The maximum adsorption capacity (𝑞_max) of 10 g/kg nZVI-treated soil was 333.3 mg/g, which was much higher than those from the other treatments of 0 (5 mg/g), 1 (25 mg/g), and 5 g/kg (125 mg/g). The underlying mechanism for Ni⁺² immobilization using nZVI in an aquatic environment is controlled by a sorption process, reduction of metal ion to zero-valent metal, as well as (co)precipitation. Moreover, increasing the nZVI treatment level in biosolids-amended soil significantly decreased bioavailable Ni⁺² concentrations in the soil.