Preparation，characterization and in vitro anti-inflammatory activity of tetrandrine-loaded chitosan-stearic acid nano micelles modified with folic acid / 中国药房

OBJECTIVE To prepare tetrandrine （TET）-loaded chitosan（CS）-stearic acid （SA） nano micelles modified with folic acid （FA）（ FA-CS-SA/TET nano micelles）， characterize them and study the anti-inflammatory effect in vitro. METHODS FA- CS-SA/TET nano micelles were prepared by ultrasonic method； the preparation technology was optimized by orthogonal test and validation test was also performed with the mass ratio of FA-CS-SA to TET， ultrasound power and ultrasound times as the factors， using the comprehensive score of entrapment efficiency （EE）， drug loading （DL） and particle size as evaluation index. FA-CS-SA/ TET nano micelles prepared by the optimal technology were characterized， and their release performance in vitro was investigated. RAW264.7 cells were used as subjects to investigate their anti-inflammatory activity in vitro. RESULTS The optimal preparation technology included that the mass ratio of FA-CS-SA to TET was 2∶1， ultrasonic power was 200 W， and the ultrasonic frequency was 200 times. The parameters of FA-CS-SA/TET nano micelles prepared by optimized technology included that EE was （98.86± 0.30）%， DL was （28.57±0.34）%， the average particle size was （227.0±9.4） nm， polydispersity index was 0.42±0.04， and the Zeta potential was（12.6±2.3）mV， respectively. The nano micelles were uniform in appearance and round in shape. The nano micelles were released quickly in 0.5% sodium dodecyl sulfate solution， with a cumulative release rate of （79.49±3.43）% within 72 hours， and its anti-inflammatory effect was stronger than that of TET raw materials. CONCLUSIONS FA-CS-SA/TET nano micelles are prepared successfully in the study， with good drug loading performance， uniform particle size， and good in vitro anti-inflammatory activity.

Research progress of nano-drug delivery system for the treatment of ocular fundus diseases / 国际眼科杂志(Guoji Yanke Zazhi)

Diseases of ocular fundus are the leading causes of severe vision impairment or even blindness in patients worldwide, and the medical treatments are seriously limited by the difficulty of therapeutic drugs entering the fundus due to the various physiological barriers. Nano-drug delivery systems, with their nanoscale size and large surface area, can be loaded with therapeutic drugs of different physicochemical properties and modified with various surface active substances, which can not only improve the solubility and penetration of the drugs, but also protect biologic drugs from degradation and improve the biological safety and bioavailability, as well as deliver therapeutic drugs to specific ocular targets. All of these make the therapeutic potential enormous. Currently, more and more studies have been carried out to take advantage of nanomaterials for the treatment of different fundus diseases, including neurodegenerative diseases, fundus neovascularization, endophthalmitis and fundus tumors. This review analyzes the challenges and barriers faced by different routes of drug administration in the treatment of fundus diseases, the physicochemical properties of common nano-drug delivery systems that have been studied in related fields, and further summarizes the progress, advantages, limitations, and future directions of the application of various nano-drug delivery systems for the treatment of ocular fundus diseases in recent years.

Boosting synergism of chemo- and immuno-therapies via switching paclitaxel-induced apoptosis to mevalonate metabolism-triggered ferroptosis by bisphosphonate coordination lipid nanogranules

Conventional chemotherapy based on cytotoxic drugs is facing tough challenges recently following the advances of monoclonal antibodies and molecularly targeted drugs. It is critical to inspire new potential to remodel the value of this classical therapeutic strategy. Here, we fabricate bisphosphonate coordination lipid nanogranules (BC-LNPs) and load paclitaxel (PTX) to boost the chemo- and immuno-therapeutic synergism of cytotoxic drugs. Alendronate in BC-LNPs@PTX, a bisphosphonate to block mevalonate metabolism, works as both the structure and drug constituent in nanogranules, where alendronate coordinated with calcium ions to form the particle core. The synergy of alendronate enhances the efficacy of paclitaxel, suppresses tumor metastasis, and alters the cytotoxic mechanism. Differing from the paclitaxel-induced apoptosis, the involvement of alendronate inhibits the mevalonate metabolism, changes the mitochondrial morphology, disturbs the redox homeostasis, and causes the accumulation of mitochondrial ROS and lethal lipid peroxides (LPO). These factors finally trigger the ferroptosis of tumor cells, an immunogenic cell death mode, which remodels the suppressive tumor immune microenvironment and synergizes with immunotherapy. Therefore, by switching paclitaxel-induced apoptosis to mevalonate metabolism-triggered ferroptosis, BC-LNPs@PTX provides new insight into the development of cytotoxic drugs and highlights the potential of metabolism regulation in cancer therapy.

Transporter-mediated Nano-delivery System in Promoting Oral Absorption of Drugs：A Review / 中国实验方剂学杂志

Oral administration is the most convenient way of drug delivery， but due to the existence of intestinal barrier， the oral bioavailability of drugs is generally low， especially for drugs with low water solubility， poor permeability and macromolecules. For decades， researchers have demonstrated that nano-delivery system is one of the most effective strategies to solve this problem， but nano-delivery systems have shown limited improvement in the oral bioavailability of drugs. Therefore， researchers have proposed to use transporter-mediated nano-delivery systems to promote the oral absorption of drugs. The intestinal tract were highly expressed as a transporter for ingesting various nutrients（such as glucose， oligopeptides and bile acids）， which was an excellent target of oral drug delivery system. Its substrate were modified on the nano-delivery system， and the loaded drugs could cross the intestinal barrier and enter the systemic circulation more efficiently through the targeting effect of transporters. At present， more and more evidences supported the potential of transporters in the field of oral drug delivery system. Therefore， this paper reviewed the research on intestinal transporters-mediated nano-delivery system to promote oral absorption of drugs， including the distribution of intestinal transporters， three strategies of transporter substrate modification， the transport properties of different types of transporters and their effects of mediating the nano-delivery system for promoting the oral absorption of drugs or treating diseases， with the aim of providing an important theoretical reference for the development of intestinal targeted nano-delivery systems.

Synthesis, characterization and protection effect of black rice anthocyanins nano-composite against hepatotoxicity induced by methotrexate in rats

Abstract The present study aimed to investigate the beneficial of prepared black rice anthocyanins nano-composite (An-AgNps) against hepatotoxicity induced by methotrexate (MTX) in rats. Anthocyanins nano-composite was prepared by silver as the metallic ion reduction and were characterized by IR and SEM. The rats in our experiment were divided into five groups. Serum lipid profile, serum transaminases (ALT and AST), ALP, LDH, TBA, GSH and SOD were examined. The results show that SEM of An-AgNps has average particle size from 70 to 130nm. In the group treated with MTX; TC, TG, LDL-c, ALT, AST, ALP, LDH and TBA levels were significantly (P0.05) increased than NC, while, HDL-c, SOD and GSH levels were significantly (P0.05) decreased. On the other hand, An-AgNps + MTX treated groups were reversed the levels of all biomarkers similar to NC. In conclusion, the results show that An-AgNps has a protective effect on MTX-induced hepatotoxicity and oxidative stress.

Resumo O presente estudo teve como objetivo investigar o benefício de nanocompósito de antocianinas de arroz preto preparado (An-AgNps) contra a hepatotoxicidade induzida por metotrexato (MTX) em ratos. O nanocompósito de antocianinas foi preparado a partir da prata por meio da redução do íon metálico e caracterizado por IR e SEM. Os ratos em nosso experimento foram divididos em cinco grupos, e foram examinados o perfil lipídico sérico, as transaminases séricas (ALT e AST), ALP, LDH, TBA, GSH e SOD. Os resultados mostram que SEM de An-AgNps tem tamanho médio de partícula de 70 a 130 nm. No grupo tratado com MTX, os níveis de TC, TG, LDL-c, ALT, AST, ALP, LDH e TBA aumentaram significativamente (P 0,05) do que NC, enquanto os níveis de HDL-c, SOD e GSH diminuíram significativamente (P 0,05). Por outro lado, nos grupos tratados com An-AgNps + MTX, foram revertidos os níveis de todos os biomarcadores semelhantes ao NC. Em conclusão, os resultados mostram que o An-AgNps tem um efeito protetor contra a hepatotoxicidade induzida pelo MTX e o estresse oxidativo.

STUDY ON THE EFFECT OF BRASS AND COPPER ELECTRODES DURING ELECTRIC DISCHARGE MACHINING OF INCONEL 718 USING NANO PARTICLES MIXED DIELECTRIC FLUID.

Electrical Discharge Machine (EDM) parameters have a significant influence on machining characteristic like material removal rate (MMR) and tool wear rate (TWR). Inconel 718, which is widely used in the Medical, Marine, Architectural and food processing industries, is used as a work material. The tool electrode materials used are brass and copper. Experiments are conducted using face centered central composite design to determine the effects of process parameters like current rate, pulse on time, pulse off time and concentration of titanium carbide nano particle in dielectric fiuid. Based upon the experimental outcomes, the effect of brass and copper electrodes during electric discharge machining of Inconel 718 using nano particles mixed dielectric fiuid was investigated.

Anti-erosion effect of an experimental varnish on eroded dentin

Abstract This in vitro study evaluated the effect of an experimental varnish containing 20% nano-hydroxyapatite (nHAP) associated with 5% stannous chloride (SnCl2) against erosive-abrasive wear on bovine dentin. Samples of bovine cervical dentin were pre-eroded (0.3% citric acid, pH 2.6 for 10 minutes) and randomized into 4 groups (n=10): Control group - experimental varnish without active ingredient (CG); experimental varnish containing 20% nHAP (nHG); experimental varnish containing 5% SnCl2 (24.800 ppm Sn2+) (SnG); experimental varnish containing 20% nHAP associated with 5% SnCl2 (18.300 ppm Sn2+) (nHSnG). After applying the materials, the erosive-abrasive challenges were performed for five days. Erosive dentin loss and analysis of the pattern of dentinal obliteration were performed by 3D confocal laser microscopy. A one-way ANOVA/Bonferroni test was performed to analyze the data (α=0.05). The SnG and nHSnG experimental groups presented more effectiveness in preventing erosive wear when compared to the other groups (p<0.05). There was no statistically significant difference between the SnG and nHSnG groups (p = 0.731) in tooth structure dentin loss. Regarding the amount of open dentinal tubules, the highest amount of obstructed dentinal tubules was demonstrated in SnG and nHSnG (p < 0.05) when compared to the others. Between SnG and nHSnG there was no significant difference (p = 0.952) in the amount of closed dentinal tubules in the dentin. Experimental varnishes containing 5% SnCl2 associated or not with 20% nHAP showed to be a promising strategy in preventing erosive-abrasive wear of dentin. In addition, nHSnG was able to obliterate dentinal tubules.

Resumo Este estudo in vitro avaliou o efeito de um verniz experimental contendo 20% de nano-hidroxiapatita (nHAP) associado a 5% de cloreto estanoso (SnCl2) contra o desgaste erosivo-abrasivo da dentina bovina. As amostras de dentina cervical bovina foram pré-erodificadas (0,3% de ácido cítrico, pH 2,6 durante 10 minutos) e aleatorizadas em 4 grupos (n=10): Grupo controle - verniz experimental sem ingrediente ativo (GC); verniz experimental contendo 20% nHAP (GnH); verniz experimental contendo 5% SnCl2 (24.800 ppm Sn2+) (GSn); verniz experimental contendo 20% nHAP associado a 5% SnCl2 (18.300 ppm Sn2+) (GnHSn). Após a aplicação dos materiais, os desafios erosivo-abrasivos foram realizados durante cinco dias. Perda de dentina erosiva e análise do padrão de obliteração dentinária foram realizadas por microscopia laser confocal 3D. Foi realizado o teste ANOVA/Bonferroni unidireccional para analisar os dados (α=0,05). Os grupos experimentais GSn e GnHSn apresentaram maior eficácia na prevenção do desgaste erosivo quando comparados com os outros grupos (p<0,05). Não houve diferença estatisticamente significativa entre os grupos GSn e GnHSn (p = 0,731) na perda de dentina da estrutura dentária. Relativamente à quantidade de túbulos dentinários abertos, a maior quantidade de túbulos dentinários obstruídos foi demonstrada em GSn e GnHSn (p < 0,05) quando comparada com os outros grupos. Entre GSn e GnHSn, não houve diferença significativa (p = 0,952) na quantidade de túbulos dentinários fechados na dentina. Os vernizes experimentais contendo 5% de SnCl2 associados ou não a 20% de nHAP mostraram ser uma estratégia promissora na prevenção do desgaste erosivo-abrasivo da dentina. Além disso, o GnHSn conseguiu obliterar os túbulos dentinários.

Effect of Calotropis procera (Aiton) Dryand.based zinc oxide nanoparticles on the cotton pest Spodoptera litura Fab

Major loss in agricultural crops is caused by insect pests. In India, various synthetic insecticides are used against pests. These are much expensive and cause environmental hazards. The nanoparticles, as an alternative approach is gaining considerable interest in this field. In the present study, we explored the biological synthesis of zinc oxide nanoparticles using Giant milkweed, Calotropis procera (Aiton) Dryand. and its effects on the tobacco cutworm, Spodoptera litura. The reduction of zinc ions (Zn2+) to zinc nanoparticles (ZnO NPs) was prepared by mixing 50 g of C. procera leaves with 100 mL of single distilled water in a 250 mL glass beaker. To synthesize nanoparticles, 50 mL of C. procera leaf extract was taken using a stirrer-heater and 5 g of zinc oxide was added at 60ºC, boiled, then kept in a hot air oven at 70ºC for 24 h. Finally, the obtained light yellow coloured powder was carefully collected and characterized using X-ray diffraction (XRD) analysis. The results revealed that the biologically synthesized zinc oxide nanoparticles pesticide was highly effective against the pest. The weight of the pest decreased from low concentration to high concentration. It is concluded that the Calotropis Procera based zinc oxide nanoparticles could be used for the control of Spodoptera litura.

Keratinase mediated fabrication and partial characterization of gold nanoparticles and its antibacterial potential

Keratinase is mainly involved in recycling of keratin waste. Of late, researchers extended its application to nanotechnology. In the present study, we have made an attempt to fabricate and characterize gold nanoparticles using crude keratinase enzyme from Serratia ficaria and also study their biological application, particularly antibacterial activity. The formation of gold nanoparticles (AuNPs) was first verified by UV-Visible Spectroscopy. FTIR spectra confirmed the presence of responsible secondary metabolites for stabilization of nanoparticles. The morphological characteristics and particle size of synthesized nanoparticles were analyzed. The AuNPs showed significant antibacterial activity against Klebsiella pneumonia, Bacillus cereus and Staphylococcus aureus. The highest radical scavenging activity, 60.62% for AuNPs was observed at 500 µg/mL. Results of this study reveals significance of keratinase application in nano-based biological applications.

Oral and nasal vaccination: current prospects, challenges, and impact of nanotechnology-based delivery systems

Abstract Currently, mucosal vaccine administration has stood out as an easier and non-invasive application method. It can also be used to induce local and systemic immune responses. In the COVID-19 pandemic context, nasal and oral vaccines have been developed based on different technological platforms. This review addressed relevant aspects of mucosal vaccine administration, with emphasis on oral and nasal vaccinations, in addition to the importance of using nanotechnology-based delivery systems to enable these strategies.

Research progress of CAR-T immunotherapy in solid tumors combined with new strategies / 中国药科大学学报

@#In recent years, the chimeric antigen receptor T-cell (CAR-T) therapy has achieved breakthrough progress in the treatment of hematologic malignancies. However, when it comes to solid tumors, numerous challenges persist.These include limited CAR-T cell infiltration, susceptibility to T cell exhaustion, off-target effects, and more.Thus, novel therapeutic strategies are imperative to enhance the efficacy of CAR-T therapy for solid tumors. In comparison to standalone CAR-T approaches, the combination of CAR-T with other tumor treatment modalities has demonstrated remarkable effectiveness in both preclinical and clinical research.This review article summarizes the advancements in combining CAR-T with various solid tumor treatments: antibody drugs, oncolytic viruses, tumor vaccines, and nanomedicines.The objective is to furnish a theoretical foundation and novel perspectives for the development of innovative CAR-T combination strategies tailored for solid tumor therapy.

Research progress of nano delivery system in breast cancer treatment / 中国药房

Breast cancer is a malignant tumor that seriously threatens women’s health at present. Although surgical treatment is the most direct and effective， it is limited by many factors and needs to be assisted by other treatments. In addition to conventional radiotherapy， these adjuvant therapies also include chemotherapy， gene therapy， phototherapy and so on. However， the therapeutic agents used in these treatment methods have some limitations， such as poor water-solubility， instability and targeting. With the development of nano-technology， more and more researchers construct and study nano delivery system for breast tumor treatment， such as response system designed based on tumor microenvironment， temperature sensitive response system， nano delivery system based on specific proteins of tumor cell membrane， etc. The author summarizes the nano delivery system， and finds that these nano delivery systems can not only improve the water-solubility and stability of the therapeutic agents， but also accurately deliver them to the breast tumor site by targeted means， improve the efficacy and reduce toxic side effects， which provides new ideas for the treatment of breast cancer in the future.

Microfluidics for nano-drug delivery systems: From fundamentals to industrialization

In recent years, owing to the miniaturization of the fluidic environment, microfluidic technology offers unique opportunities for the implementation of nano drug delivery systems (NDDSs) production processes. Compared with traditional methods, microfluidics improves the controllability and uniformity of NDDSs. The fast mixing and laminar flow properties achieved in the microchannels can tune the physicochemical properties of NDDSs, including particle size, distribution and morphology, resulting in narrow particle size distribution and high drug-loading capacity. The success of lipid nanoparticles encapsulated mRNA vaccines against coronavirus disease 2019 by microfluidics also confirmed its feasibility for scaling up the preparation of NDDSs via parallelization or numbering-up. In this review, we provide a comprehensive summary of microfluidics-based NDDSs, including the fundamentals of microfluidics, microfluidic synthesis of NDDSs, and their industrialization. The challenges of microfluidics-based NDDSs in the current status and the prospects for future development are also discussed. We believe that this review will provide good guidance for microfluidics-based NDDSs.

Application of PDX model in the evaluation of nano-delivery systems / 药学学报

Malignant tumor is a major disease affecting human health. The nano-delivery system itself has a unique size effect and it can achieve tumor-targeted distribution of drug molecules, improve the therapeutic effect, and reduce the toxic and side effects on normal tissues and cells after functional modification. Patient-derived xenografts (PDX) models can be established by transplanting patient-derived cancer cells or small tumor tissue into immunodeficient mice directly. Compared with the tumor cell line model, this model can preserve the key features of the primary tumor such as histomorphology, heterogeneity, and genetic abnormalities, and keep them stable between generations. PDX models are widely used in drug evaluation, target discovery and biomarker development, especially providing a reliable research platform for the diagnosis and treatment evaluation of nano-delivery systems. This review summarizes the application of several common cancer PDX models in the evaluation of nano-delivery systems, in order to provide references for researchers to perform related research.

Advance on small molecule self-assembled nano-drug delivery system / 药学学报

Since the application of biomedical nanotechnology in the field of drug delivery breathes new life into the research and development of high-end innovative agents, a substantial number of novel nano-drug delivery systems (nano-DDSs) have been successively developed and applied in the clinical practice. Among them, small molecule pure drug and prodrug-based nanoassemblies have grasped great attention, owing to the facile fabrication, ultrahigh drug loading and feasible industrial production. Herein, we provide an overview on the latest updates of small-molecule nanoassemblies. Firstly, the self-assembled prodrug-based nano-DDSs are introduced, including nanoassemblies formed by amphiphilic monomeric prodrugs, hydrophobic monomeric prodrugs and dimer monomeric prodrugs. Then, the recent advances on nanoassemblies of small molecule pure chemical drugs and biological drugs are presented. Furthermore, carrier-free small-molecule hybrid nanoassemblies of pure drugs and/or prodrugs are summarized and analyzed. Finally, the rational design, application prospects and clinical challenges of small-molecule self-assembled nano-DDSs are discussed and highlighted. This review aims to provide scientific reference for constructing the next generation of nanomedicines.

Advances in applications of molecular dynamics simulation techniques to the research of self-assembled nano-drug delivery systems / 药学学报

Molecular dynamics simulation technology relies on Newtonian mechanics to simulate the motion of molecular system of the real system by computer simulation. It has been used in the research of self-assembly processes illustration and macroscopic performance prediction of self-assembly nano-drug delivery systems (NDDS) in recent years, which contributes to the facilitation and accurate design of preparations. In this review, the definitions, catalogues, and the modules of molecular dynamics simulation techniques are introduced, and the current status of their applications are summarized in the acquisition and analysis of microscale information, such as particle size, morphology, the formation of microdomains, and molecule distribution of the self-assembly NDDS and the prediction of their macroscale performances, including stability, drug loading capacity, drug release kinetics and transmembrane properties. Moreover, the existing applications of the molecular dynamic simulation technology in the formulation prediction of self-assembled NDDS were also summarized. It is expected that the new strategies will promote the prediction of NDDS formulation and lay a theoretical foundation for an appropriate approach in NDDS studies and a reference for the wider application of molecular dynamics simulation technology in pharmaceutics.

Application and mechanism of nanomedicine and nanomaterials in antibacterial infection therapy / 药学学报

Antibacterial therapy is a global health issue. The antibiotic resistance is becoming an increasingly serious threat, which caused by misuse and overuse of antibacterial agents combined with the emergence of new resistance mechanism. The resulting infection treatment risk and incidence of the spread of disease, severe cases and deaths are increased in different degrees. With the extensive application of biomaterials and nanotechnology to biomedicine, extensive research has been conducted on antibacterial infection. With the specific physicochemical properties like optical, electric and magnetic and high penetration, inorganic nanomaterials can produce natural antibacterial effect. Nanomedicine can be designed to allow controlled drug release and targeting effect, thus demonstrated better antibacterial efficiency. In this review, the mechanism of antibacterial resistance is described, and the antibacterial infection research on inorganic nanomaterials, as well as nano-drug delivery system including liposomes, nanoparticles, dendrimers and biomimetic nanocarriers are summarized. Nanomaterials and nanotechnology offer promising strategies for the development of new agents that can improve efficacy on antibacterial infections and overcome antibiotic resistance potentially.

Advance of hair follicle targeted drug delivery systems in the treatment of acne and hair loss / 药学学报

Hair follicle (HF), one of the skin appendages, has received a lot of attention to be a new target and pathway for drug delivery. The development of hair follicle targeted drug delivery system (HFTDDS) through percutaneous permeation is particularly important for skin diseases derived from HF such as acne, hair loss, and folliculitis for their on-site action. This review describes the structure and physiological function of HF, the microenvironment of HF, and factors affecting HF permeation. Multiple nanoformulations used to improve the HF permeation and technologies to characterize the HF permeation were introduced. The latest advance of HFTDDS based on nanoformulations were systematically summarized and analyzed in the treatment of acne and hair loss. Finally, the challenges of formulating HFTDDS were discussed. The review is expected to provide some ideas and references for developing delivery systems for treating skin diseases derived from HF.

Research progress of platelets and their derivatives based drug delivery systems / 中国输血杂志

Platelets play an important role in physiological and pathological activities such as thrombosis, inflammation and tumorigenesis. At present, the application of platelets in drug delivery systems is increasingly studied. Compared with traditional drug delivery systems, new drug delivery systems based on platelets and their derivatives can effectively improve the circulation time and selective accumulation, and reduce the occurrence of related immune reactions or off-target toxic and side effects. In this paper, the types and applications of platelet and its derivatives drug delivery systems were summarized in order to provide reference for platelet-related drug delivery research.

Research progress in biomimetic nano formulations of biofilms / 中国药科大学学报

@#Biomimetic nano formulations of biofilms have low immunogenicity, high targeting, and good biocompatibility, and can avoid being cleared by the endothelial reticular system, thus with in longer blood circulation time in the body.This article mainly reviews the main types as well as advantages and disadvantages of biomimetic nano formulations of biofilms, including tumor cell membranes, red blood cell membranes, platelet membranes, white blood cell membranes, stem cell membranes, extracellular vesicles (exosomes, microvesicles, and apoptotic bodies), endoplasmic reticulum membranes, and composite biofilms, with also a prospect of the challenges facing biomimetic nano formulations of biofilms and their future development based on their current research status, aiming to provide some insight for further research on biomimetic nano formulations of biofilms.