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.

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.

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.

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.

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.

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.

Efficacy of the photon-induced photoacoustic streaming combined with nano-silver solution on Enterococcus faecalis in root canals / 口腔医学

Objective@#o explore the antibacterial effect of combined use of photon-induced photoacoustic streaming (PIPS) and silver nanoparticles (AgNPs) on Enterococcus faecalis biofilm in root canals.@*Methods@#A total of 36 isolated teeth with single root canal were collected to establish an experimental root canal model of Enterococcus faecalis infection. Samples were randomly divided into six groups and 0.9% NaCl, 2% NaClO, 0.1% AgNPs solutions were used with conventional needle irrigation (CNI) or PIPS for root canals. Colony count method was used to measure the number of Enterococcus faecalis biofilm in root canals before and after treatment, and the percentage of colony count reduction was calculated.@*Results@#The inhibitory effect of Enterococcus faecalis biofilm in all experimental groups was stronger than that in the control group (P<0.05). The decrease amplitude of 0.9% NaCl, 2% NaClO, 0.1% AgNPs assisted with PIPS was greater than that of 0.9% NaCl, 2% NaClO, 0.1% AgNPs assisted with CNI (P<0.05). The decrease in the 0.1% AgNPs assisted with PIPS group was significantly greater than that in the 2% NaClO assisted with PIPS group (P<0.05).@*Conclusion@#PIPS-assisted AgNPs solution washing can significantly improve the effect of clearing Enterococcus faecalis biofilm in root canals.

Research progress of biomimetic nano drug delivery system in nervous system disease / 药学学报

Brain delivery of drugs remains challenging due to the presence of the blood-brain barrier (BBB). With advances in nanotechnology and biotechnology, new possibilities for brain-targeted drug delivery have emerged. Biomimetic nano drug delivery systems with high brain-targeting and BBB-penetrating capabilities, along with good biocompatibility and safety, can enable 'invisible' drug delivery. In this review, five different types of biomimetic strategies are presented and their research progress in central nervous system disorders is reviewed. Finally, the challenges and future prospects for biomimetic nano drug delivery systems in intracerebral drug delivery are summarized.

Transdermal drug delivery technology for brain-targeted drug delivery / 药学学报

Intracerebral delivery of drugs for the treatment of central nervous system disorders is usually limited by the blood-brain barrier (BBB). Transdermal drug delivery systems (TDDS) have the advantage of improving patient compliance and avoiding first-pass effects compared to intravenous, oral and intranasal drug delivery, and are an emerging non-invasive drug delivery route that facilitates long-term drug delivery to patients. The discovery of direct subcutaneous targeting of lymphatic pathways to brain tissue has made TDDS a new brain-targeted drug delivery strategy. At the same time, the development of nano-delivery technology has further facilitated the application of TDDS for targeted drug delivery to the brain. This review summarizes the mechanism of transdermal drug delivery into the brain and the application of TDDS in the treatment of brain diseases, providing new ideas and methods for the treatment of central nervous system diseases.

Immune effects of nano-tumor vaccine against melanoma in mice / 中国生物制品学杂志

@#Objective To investigate the anti-melanoma immune effects of nano-tumor vaccine based on nano-adjuvant[CpG-coated nanoparticles(CNP)] and melanoma cell lysate antigen.Methods The immunoregulatory effects of CNP and melanoma cell lysate antigens on bone marrow-derived dendritic cells(BMDCs) and the regulatory effects on expression and secretion of cytokines IL-6 and IL-12 were investigated.After the mice inoculated with melanoma cells formed tumor,40C57BL/6N fermale mice with similar size of tumor were randomly divided into 4 groups:control(PBS) group,adjuvant(CNP) group,lysate(Lysate) group and vaccine(CNP+Lysate) group,which were administered subcutaneously once a week for 3 weeks.The tumor size of mice was recorded every 3 d and the tumor growth curve was drawn.The peripheral blood of mice was collected to detect the contents of IFN_γ and TNF_α,and immunohistochemical method was used to detect the infiltration of CD8~+T lymphocytes in tumor tissues.Results Compared with PBS,CpG and tumor lysate antigen groups,nano-vaccine adjuvant CNP effectively stimulated BMDCs maturation and promoted IL-6 and IL-12 secretion;Nanotumor vaccine showed good anti-tumor activity in vivo, the tumor size of mice in vaccine group decreased significantly,and the secretion levels of IFN_γ and TNF-α in serum were significantly higher than those in other groups;The infiltration of CD8~+T lymphocytes in tumor tissues of mice in vaccine group was also significantly better than that in other groups.Conclusion Nano-tumor vaccine effectively activated BMDCs,highly expressed immune factors,and also effectively inhibited tumor growth,showing good application potential.

Analysis of the application of nano-carbon lymphatic tracer technology in laparoscopic radical resection of colon cancer based on propensity matching / 中国医师进修杂志

Objective:To analyze the application effect of nano-carbon lymphatic tracer technology in laparoscopic colon cancer (CC) radical resection based on propensity matching.Methods:Retrospective case-control study was performed in this study. From January 2016 to April 2021, 714 cases of CC patients who underwent laparoscopic CC radical resection in Kunshan Second People′s Hospital were divided into groups according to whether or not the nano-carbon lymphatic tracing technique was applied. Seventy-eight cases in group A were applied with nano-carbon lymphatic tracing technique, while 636 cases in group B were not applied with nano-carbon lymphatic tracing technique. The initial data were matched 1∶3 by the propensity score matching method, and finally group A (73 cases) and group B (219 cases) were obtained. The detection of lymph nodes in the two groups after propensity score matching was compared.Results:By comparing the baseline data of the two groups after propensity score matching, it was found that there were no significant differences in gender, height, weight, body mass index, tumor T stage, tumor N stage, tumor TNM stage, preoperative chemotherapy, or tumor location ( P>0.05). The total number of lymph nodes in group A was higher than that in group B: (22.24 ± 7.08) pieces vs. (19.03 ± 6.29) pieces, and the difference was statistically significant ( t = 3.66, P<0.05); the number of positive lymph nodes and the degree of lymph node metastasis in group A were not significantly different from those in group B ( P>0.05). Tumor T stage T 3, tumor N stage N 0, tumor TNM stage Ⅱ, and preoperative chemotherapy, the total number of lymph nodes in group A was higher than that in group B: 23 (6, 60) pieces vs. 19 (4, 54) pieces , 20 (3, 62) pieces vs. 18 (3, 75) pieces, 23 (6, 59) pieces vs. 20 (7, 54) pieces, 22 (5, 45) pieces vs. 14 (4, 46) pieces, and the difference was statistically significant ( Z = 2.43, 2.70, 2.64 and 3.32; P<0.05); the number of positive lymph nodes and the degree of lymph node metastasis of tumor N stage N 2 in group A were lower than those in group B: 4 (4, 9) pieces vs. 6 (4, 25) pieces , 16 (10, 42) pieces vs. 32 (19, 100) pieces, and the difference between groups was statistically significant ( Z = -2.53 and -2.87, P<0.05). Followed up to April 2022, among the 292 patients, 5 were lost to follow-up, the 3-year disease-free survival rates of 72 patients in group A and 215 patients in group B were 83.33% (60/72) and 91.16% (196/215) respectively, there was no significant difference between two groups ( P>0.05). Conclusions:The number of lymph nodes detected in laparoscopic CC radical resection increases after the application of nano-carbon lymphatic tracing technology.

Clinical application study of parathyroid autofluorescence in identification of parathyroid gland in thyroid carcinoma surgery / 中华内分泌外科杂志

Objective:To observe the application of near-infrared autofluorescence imaging (NIRAF) technology combined with carbon nanoparticle (CNP) negative imaging in identification of parathyroid gland (PG) during thyroid carcinoma surgery.Methods:80 patients with thyroid cancer who underwent total thyroidectomy + central lymph node dissection performed by the same experienced physician team at the 960th Hospital of the PLA from Jan. to Mar. 2022 were prospectively included. Before operation, they were divided into two groups using random number table method before surgery: control group (40 cases) using CNP negative imaging, and experimental group (40 cases) using CNP negative imaging combined with NIRAF technique for intraoperative identification of PG. The gold standard for the identification of parathyroid glands was to compare the amount of intraoperative discovery retention misresection and transplantation of PG and the number of postoperative parathyroid hormone (PTH) and the number of complications in the two groups by immune colloidal gold technique. SPSS 25.0 software was used for statistical analysis.Results:All patients in the two groups were successfully operated and followed up. 137 149 PG were found and confirmed in the control group and the observation group, 108 132 PG were retained in situ and 29 17 PG were transplanted, the differences were statistically significant (all P <0.05) ; The number of A1 PG was 103 and 109, respectively. Among them, 84 102 were retained in situ and 19 7 were transplanted, the difference was statistically significant ( P <0.05) . There was no significant difference in the amount of A2 type PG and B type PG between the two groups ( P >0.05) . No A3 type PG was found in the two groups, and a total of 3 A3 types of PG were confirmed in postoperative pathological reports. There were no significant differences in misresection in the control group and the observation group, 5 and 2 PG were mistakenly cut, respectively (all P >0.05) . The PTH 1 day after surgery was 17.7 (5.6,30.4) pg/mL in the control group and 21.7 (12.8,38.3) pg/mL in the observation group, the difference was statistically significant ( P<0.05) . There were no significant differences in the levels of serum calcium and serum phosphorus 1 day after operation and PTH 1 month after surgery between the two groups (all P > 0.05) . Conclusion:Compared with CNP alone, combined with NIRAF technique can quickly and effectively identify PG, and PG can be better protected in situ and postoperative hypoparathyroidism can be reduced.

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.

Allergic reactions of COVID-19 vaccine based on mRNA-LNP and its pharmacokinetics in vivo / 药学学报

Vaccination has been proved to be the most effective strategy to prevent the Corona Virus Disease 2019 (COVID-19). The mRNA vaccine based on nano drug delivery system (NDDS) - lipid nanoparticles (LNP) has been widely used because of its high effectiveness and safety. Although there have been reports of severe allergic reactions caused by mRNA-LNP vaccines, the mechanism and components of anaphylaxis have not been completely clarified yet. This review focuses on two mRNA-LNP vaccines, BNT162b2 and mRNA-1273. After summarizing the structural characteristics, potential allergens, possible allergic reaction mechanism, and pharmacokinetics of mRNA and LNP in vivo, this article then reviews the evaluation methods for patients with allergic history, as well as the regulations of different countries and regions on people who should not be vaccinated, in order to promote more safe injection of vaccines. LNP has become a recognized highly customizable nucleic acid delivery vector, which not only shows its value in mRNA vaccines, but also has great potential in treating rare diseases, cancers and other broad fields in the future. At the moment when mRNA-LNP vaccines open a new era of nano medicine, it is expected to provide some inspiration for safety research in the process of research, development and evaluation of more nano delivery drugs, and promote more nano drugs successfully to market.

Preparation, pharmacokinetics and pharmacodynamics of curcumin nano emulsion / 药学实践杂志

Objective To explore the pharmacokinetic properties of curcumin nano emulsion and its pharmacodynamic effects on hyperlipidemia in rats. Methods The method for determination of curcumin was established by HPLC-MS. The pharmacokinetics characteristics of curcumin nano emulsion oral administration system were investigated. SD rats were used as model animals to establish hyperlipidemia animal models, and the pharmacodynamic effects of curcumin nano emulsion on hyperlipidemia induced by high fat diet was preliminarily investigated. Results The results of pharmacokinetic studies in vivo showed that the relative bioavailability of curcumin nano emulsion was 313.47% with bulk drug group as the reference preparation. The relative bioavailability of curcumin nano emulsion was 279.52 % with tablets as reference preparation. Cmax of curcumin nano emulsion group was 201.48 % of that of bulk drug group and 193.02 % of that of tablet group, and had higher MRT value (183.52 % of that of bulk drug group and 154.21 % of that of tablet group) than bulk drug group and tablet group. Pharmacodynamics research results showed that curcumin nano emulsion oral administration system could significantly reduce the levels of triglyceride and LDL-c in serum of model rats, and relieve liver lipid deposition and liver injury caused by high-fat diet in model animals. Conclusion The oral administration system of curcumin nano emulsion could effectively improve the bioavailability of curcumin, which has a good hypolipidemic effect. It also could control the weight gain of hyperlipidemia rats and improve the changes of liver coefficient caused by lipid metabolism disorder.

Efficacy of Jiangsha Banxia nano-paste on nausea and vomiting in end-stage patients and its effect on QOL in cancer patients / 药学实践杂志

Objective To observe the clinical efficacy of Jiangshabanxia nano-paste on nausea and vomiting in end-stage patients and its effect on the quality-of-life (QOL) in cancer patients. Methods 120 end-stage patients with nausea and vomiting symptoms above grade III were randomly divided into observation group and control group. They were treated with Jiangshabanxia nano-paste and placebo paste respectively. The paste patch was changed every 24 hours and used continuously for 7 days. The nausea and vomiting symptom score, the quality-of-life measurement score and KPS score of cancer patients in the two groups were observed to evaluate the curative effect. Results After 7 days of treatment, the symptom scores of nausea and vomiting in the observation group decreased significantly, the KPS score of the observation group increased, and the effective rate was higher than that in the control group. The score of QOL measurement showed that after treatment, the score of main symptom areas and other symptom areas (except external dyspnea, diarrhea and economic difficulties) in the observation group decreased, and the score of overall health area increased. After treatment, the score of main symptom areas and other symptom areas (except external dyspnea, diarrhea and economic difficulties) in the observation group was lower than that in the control group, and the scores of overall health area in the observation group were higher than those in the control group. Conclusion Jiangshabanxia nano-paste has a good clinical efficacy nausea and vomiting in end-stage patients, it also can improve the quality of life end-stage cancer patients.

Anti-tumor Effect of Alkaloids of Chinese Medicine： A Review / 中国实验方剂学杂志

Malignant tumors， with the increasing crude morbidity and mortality year by year， have become the major diseases threatening human health. The conventional therapeutic drugs against tumors have serious adverse reactions， which can cause a heavy burden on patients. The active components of Chinese medicine can effectively inhibit tumor growth， improve the quality of life of patients， and have few toxic and side effects. Alkaloids of Chinese medicine are natural organic compounds widely existing in a variety of Chinese herbal medicines. In recent years， they have attracted more and more attention because of their anti-tumor effect. The anti-tumor mechanisms of alkaloids of Chinese medicine mainly include the induction of apoptosis， inhibition of tumor cell migration and invasion， suppression of proliferation， induction of autophagy of tumor cells， cell cycle arrest， inhibition of tumor angiogenesis， regulation of microRNA， and modulation of immunity. In addition， Chinese medicine alkaloids can also reverse tumor drug resistance and reduce the stemness of tumor stem cells. Alkaloids of Chinese medicine can regulate the phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， c-Jun N-terminal kinase （JNK）， p38 mitogen-activated protein kinase （p38 MAPK）， mammalian target of rapamycin （mTOR）， Notch， Hedgehog， Wnt/β-catenin， and other signaling pathways to participate in the processes of tumor proliferation， invasion and metastasis， autophagy and apoptosis， and affect the occurrence and development of tumors in multiple links and ways. The derivatives and nano-preparations of alkaloids can improve the solubility， utilization， and anti-tumor activity of alkaloids， bringing a broader prospect for the clinical application of alkaloids. This review summarized the recent anti-tumor research on alkaloids， their representative derivatives， and nano-preparations to provide references for the in-depth research on the anti-tumor effect of alkaloids.