Nebulized anionic guanidinylated O-carboxymethyl chitosan/N-2-hydroxypropyltimehyl ammonium chloride chitosan nanoparticles for siRNA pulmonary delivery: preparation,characterization and in vitro evaluation

This study developed a pH-sensitive anionic system composed of guanidinylated O-carboxymethyl chitosan (GOCMCS) and N-2-hydroxypropyltimehyl ammonium chloride chitosan (N-2-HACC) for efficient siRNA delivery to the lungs following nebulization. About 16.8% of guanidine groups were incorporated into O-carboxymethyl chitosan (OCMCS) with the aid of O-methylisourea. Gel electrophoresis images demonstrated that siRNA was successfully encapsulated in nanoparticles ranging from 150 to 180?nm with zeta potential of about ?17?mV. The nanoparticles containing GOCMCS existed superior transfection performance compared with their amino-based analogs. The evaluation in vitro revealed that nanoparticles were internalized into A549 cells by energy-dependent endocytosis, then achieved endosomal escape by direct transmembrane penetration of guanidine moieties as well as swelling behavior of nanoparticles due to the pH sensitivity of GOCMCS. The mRNA level of survivin gene was down-regulated to 6.9% using GOCMCS/N-2-HACC/siSurvivin NPs. The survivin siRNA mediated by nanoparticles caused 30% of cell growth inhibition and induced 19.45% of cell apoptosis, which was comparable to Lipofectamin2000. After nebulization of siRNA-loaded nanoparticles, the stability of siRNA was maintained and fine particle fractions were detected by two-stage impinger that accounted for more than 60%. These results suggested that GOCMCS/N-2-HACC nanoparticles possessed potential as safe and efficient carrier for siRNA pulmonary delivery.     

Biogenic silver,gold and copper nanoparticles - A sustainable green chemistry approach for cancer therapy

The advent of nanotechnology has revolutionized the way clinicians are treating cancers. Treatment for cancer includes surgery, radiotherapy, hormonal therapy, chemotherapy, and now nano therapy, which could be a possible alternative. This new treatment regime can be beneficial since it shows minimum side effects as compared to other treatment methods. Metallic nanoparticles synthesized through green chemistry by using biological entities minimizes the side effects and enhances the properties of the metal against cancer cells. These green nanoparticles are widely used in research and have shown promising cytotoxic activity against various cancer cell lines. Mechanistically, these nanoparticles can enter the cancer cell and cause cell death by the activation of various molecular pathways such as apoptosis, necrosis and autophagy. This review focuses on the metal nanoparticles (silver, gold and copper) synthesized by the green chemistry approach that have been utilized to study the cancer cell death and we are also discussing the underlying molecular pathways.     

Influences of opioids and nanoparticles on in vitro wound healing models

For efficient pain reduction in severe skin wounds, topical opioids may be a new option – given that wound healing is not impaired and the vehicle allows for slow opioid release, since long intervals of painful wound dressing changes are intended. We investigated the influence of opioids on the wound healing process via in vitro models, migration assay and scratch test. In fact, morphine, hydromorphone, fentanyl and buprenorphine increased the number of migrated HaCaT cells (spontaneously transformed keratinocytes) twofold. In the scratch test, morphine accelerated the closure of a monolayer wound (scratch). As possible slow release application forms are nanoparticulate systems like solid lipid nanoparticles (SLN) and dendritic core-multishell (CMS) nanotransporters, we evaluated the effect of unloaded nanoparticles on HaCaT cell migration, too. CMS nanotransporters did not inhibit migration, SLN even enhanced it (twofold). Applying morphine plus unloaded nanoparticles reduced morphine effects possibly due to uptake into CMS nanotransporters and adsorption to the surface of SLN. In contrast to SLN, TGF-β1 was taken up by CMS nanotransporters, too. Both nanoparticles are tolerable by skin and eye as derived from Episkin-SM^TM skin irritation test and HET-CAM assay. No acute toxic effects were observed either. In conclusion, opioids as well as the investigated nanoparticulate carriers conform the essential conditions for topical pain reduction.     

Eco-friendly design of TiO2 nanoparticles supported on Fe3O4 coated carbon-based biochar substrate for the synthesis of pyrano-[2, 3-c]-pyrazole derivatives

The novel naturally based magnetic biochar/Fe₃O₄–TiO₂ nanocatalyst was developed, characterised, and used to manufacture biologically active dihydropyrano-[2,3-c]-pyrazole [DHPP] derivatives. The one-pot four-component reaction between hydrazine hydrate, malononitrile, ethyl acetoacetate, and various aromatic aldehydes was carried out to synthesize the DHPP. The reaction was carried out in the presence of H₂O:EtOH (1:1) as solvent at 60 °C with excellent yield (91–98%). This operationally simple approach has numerous benefits, including a green and clean reaction profile, easy workup and purification methods, a very fast reaction time, high atom efficiency, and low cost as well as magnetically separable nanocatalyst. XRD, FT-IR, TGA, HR-TEM, FE-SEM, EDAX, VSM were used to characterize the nanocatalyst and ¹³C NMR, ¹H NMR, and mass spectrometry were investigate to studies the structure of products. Antimicrobial activity was tested on the resulting products (5a-5l). According to the data, the synthesized compounds were found to have substantial antimicrobial activities against the Gram-positive bacteria S. aureus and S. phyogens, Gram-negative bacteria E. coli and P. aeruginosa, and fungi Candida albicans.     

甘精胰岛素不同给药时间治疗1型糖尿病的疗效及安全性研究

目的：探讨不同时间皮下注射甘精胰岛素治疗1型糖尿病的疗效及安全性。方法选取50例1型糖尿病患者,应用门冬胰岛素联合甘精胰岛素进行治疗,在甘精胰岛素不改变用量前提下,给药时间由22：00调整到18：00前后,比较时间调整前后3 d患者空腹血糖（ FBG）、早中晚餐后2 h血糖（2hPG）和午餐前血糖的变化情况、门冬胰岛素的用量及午餐前患者低血糖事件发生情况。结果甘精胰岛素调整用药时间后,患者午餐前血糖调整至理想水平,FBG（7．28±2．13）mmol/L比（8．33±2．20）mmol/L、午餐后2hPG下降显著（8．61±2．59）mmol/L 比（9．70±1．75）mmol/L（U＝2．425、3．034,均 P＜0．05）,早餐后2hPG （8．27±2.02）mmol/L比（8．56±2．33）mmol/L和晚餐后2hPG（9．54±1．55）mmol/L比（9．61±1．75）mmol/L变化均不明显（均P＞0．05）;门冬胰岛素早餐前用量减少,午餐前和晚餐前用量增加;午餐前低血糖事件显著减少（χ2＝4．105、5．005,均P＜0．05）。结论甘精胰岛素联合门冬胰岛素治疗1型糖尿病患者,在不改变甘精胰岛素用量情况下,给药时间由22：00调整为18：00,可平稳降低空腹血糖,减少午餐前低血糖的发生。     

Magnetism in drug delivery: The marvels of iron oxides and substituted ferrites nanoparticles

In modern drug delivery, seeking a drug delivery system (DDS) with a modifiable skeleton for proper targeting of loaded actives to specific sites in the body is of extreme importance for a successful therapy. Magnetically guided nanosystems, where particles such as iron oxides are guided to specific regions using an external magnetic field, can provide magnetic resonance imaging (MRI) while delivering a therapeutic payload at the same time, which represents a breakthrough in disease therapy and make MNPs excellent candidates for several biomedical applications. In this review, magnetic nanoparticles (MNPs) along with their distinguishable properties, including pharmacokinetics and toxicity, especially in cancer therapy will be discussed. The potential perspective of using other elements within the MNP system to reduce toxicity, improve pharmacokinetics, increase the magnetization ability, improve physical targeting precision and/or widen the scope of its biomedical application will be also discussed.     

莫沙必利联合胰激肽原酶治疗糖尿病神经源性膀胱的疗效及安全性分析

目的 探讨莫沙必利联合胰激肽原酶治疗糖尿病神经源性膀胱(DNB)的疗效及安全性.方法 将120例糖尿病神经源性膀胱患者采用数字表法随机分为对照组和观察组,各60例.两组患者均接受基础治疗,包括降糖、降压、营养神经以及调节血脂等,观察组在此基础上加用莫沙必利与胰激肽原酶治疗,两组治疗时间均为3周.观察两组疗效、血糖、血脂、尿动力学、生活质量以及不良反应发生率.结果 观察组总有效率为93.33％,明显高于对照组的65.00％(χ2=14.602,P＜0.0l);观察组不良反应发生率为8.33％,明显低于对照组的20.00％(χ2=11.368,P＜0.01).结论 莫沙必利联合胰激肽原酶治疗糖尿病神经源性膀胱的疗效显著,能够明显改善患者的临床症状及提高患者的生活质量,应在临床上加以推广并应用.     

The safety and efficacy of the use of oral anticoagulant medications in patients with diabetes mellitus: A systematic review

AimsDiabetes mellitus (DM) and atrial fibrillation (AF) commonly co-exist. Oral anticoagulants (OACs) are widely used in patients with DM. This review aims to summarise the available literature on the safety (hypoglycaemia or bleeding) and efficacy (stroke or systemic embolism) of the use of OACs in patients with DM.MethodsWe searched the Medline, the Excerpta Medica dataBASE (Embase) and Cochrane databases up to the 10th of December 2020. The search strategy was conducted using both keywords and MeSH terms. We included randomised controlled trials (RCTs) and observational studies that reported on the safety and efficacy of the use of OACs in patients with diabetes from all age groups. Study selection, data extraction and quality assessment were conducted independently by two reviewers.ResultsA total of 3,976 articles were identified through the search process, of which seven studies met the inclusion criteria of the systematic review: four observational studies and three studies that were randomised controlled trials, with a total of 703,855 patients. Two observational studies reported that the use of warfarin was associated with a higher risk of hypoglycaemic events, specifically with sulfonylurea. One observational study and three randomised controlled trials reported that the use of warfarin compared to other oral anticoagulants was associated with a higher risk of bleeding. In addition, three randomised controlled trials reported that the use of warfarin compared to other oral anticoagulants was associated with a lower risk of stroke or systemic embolism.ConclusionsThis systematic review found that DOACs had a better efficacy outcome and safer clinical outcomes in comparison to warfarin in patients with diabetes.     

Catalytic applications of hydrotalcite and related materials in multi -component reactions: Concepts,challenges and future scope

Hydrotalcites (HTs) are the potential substitute to conventional base catalysts. HTs are useful in efficient syntheses of various heterocycles, such as chromenes, pyrans, pyrazoles, triazoles, using multi-component reactions. This review focuses on the chemistry of HTs and particularly hydrotalcites and related materials in the synthesis of heterocycles. The effects of preparation method and, physico-chemical parameters, such as calcination, molar ratio of metals, role of intercalated ions, surface area, on the catalytic activities are discussed. Along with technical aspects, this review also unlocks various untouched areas in developing sustainable catalyst for syntheses of heterocycles, drugs, etc. for the future.     

Directly reusing waste fish scales for facile,large-scale and green extraction of fluorescent carbon nanoparticles and their application in sensing of ferric ions

Fluorescent nanomaterials have important applications in environmental monitoring and biomedicine and imaging. However, their preparation often is cumbersome, expensive, and extremely small-scale, requires harsh conditions, which limit their wide and practical applications. Herein, by directly reusing waste fish scales with intrinsic fluorescent property as precursors, we developed a facile, large-scale, inexpensive, and green method for extraction of fluorescent carbon nanoparticles for sensing of Fe³⁺. Our preparation approach only requires soaking fish scales in water without harsh conditions and complicated operations, only based on physical exfoliation, not limited by containers. Fish-scale-derived fluorescent carbon nanoparticles with bright blue fluorescence and a quantum yield of 15.6% are irregular spheres with a diameter of more than 60 nm, contained smaller nanodots with a diameter of about 4.2 nm, which has obvious lattice fringes of 0.23 nm. Elemental and functional group analysis confirmed that fluorescent carbon nanoparticles were mainly composed of C, O, and N, had hydroxyl, amine, and carbonyl groups, and similar in composition to collagens and hydroxyapatites. Fluorescent carbon nanoparticles can be used for fluorescent quenching-based detection of Fe³⁺ with a linear range of 0–6.25 μM and detection limit of 0.144 μM, and have good recoveries for Fe³⁺ in actual water samples and human serum with low relative standard deviations. This study not only adds a new dimension to provide a large-scale, simple, green, and promising method for reuse of waste fish scales, but also offers a new idea for the large-scale preparation and application of fluorescent carbon nanomaterials.     

Ultrasound-assisted extraction for rapid determination of Zn,Cu, Fe,Mg and Mn in liver of diabetic rats under different antioxidant treatments

The metabolism of several essential elements is altered in diabetes mellitus and these nutrients might have specific roles in the pathogenesis and progress of this disease, nevertheless, the mechanisms are still far from known.     

The efficacy,safety and tolerability of pantoprazole-based one-week triple therapy in H. pylori eradication and duodenal ulcer healing

SUMMARY

Objective: Recently, proton pump inhibitor (PPi)-based triple therapy has been recommended as a first line treatment in the eradication of Helicobacter pylori. The aim of this open, multicentre trial was to investigate the efficacy, safety, tolerability and the ulcer healing rate of a triple regimen consisting of pantoprazole^? 40?mg, clarithromycin 500?mg and amoxicillin 1000?mg twice daily for 7?days, in the eradication of H. pylori in patients with duodenal ulcer in Turkey.

Research design and methods: H. pylori infection was assessed by histological examination and rapid urease test at baseline and 4?weeks after the completion of the therapy. Seventy-seven patients were enrolled, 5 were excluded due to various reasons and 72 completed the entire course of the trial.

Results: H. pylori eradication was confirmed in 49 of these patients; the eradication rate was 68% by per-protocol analysis and 63.6% by intention-to-treat analysis. The ulcers were completely healed in 61 patients (85%) at the second endoscopic examination. Drug compliance was excellent (97.3%) and there were no serious adverse events.

Conclusion: Pantoprazole-based 1-week triple therapy was well tolerated and the ulcer healing rate was high (85%). Relatively low H. pylori eradication rates may be attributed to rising antibiotic resistance over recent years. A large scale, comparative study with other PPi-based regimens is warranted based on the results of this open study with the pantoprazole-based regimen.     

PLGA nanoparticles for the oral delivery of nuciferine: preparation,physicochemical characterization and in vitro/in vivo studies

This article reports a promising approach to enhance the oral delivery of nuciferine (NUC), improve its aqueous solubility and bioavailability, and allow its controlled release as well as inhibiting lipid accumulation. NUC-loaded poly lactic-co-glycolic acid nanoparticles (NUC-PLGA-NPs) were prepared according to a solid/oil/water (s/o/w) emulsion technique due to the water-insolubility of NUC. PLGA exhibited excellent loading capacity for NUC with adjustable dosing ratios. The drug loading and encapsulation efficiency of optimized formulation were 8.89?±?0.71 and 88.54?±?7.08%, respectively. NUC-PLGA-NPs exhibited a spherical morphology with average size of 150.83?±?5.72?nm and negative charge of ?22.73?±?1.63?mV, which are suitable for oral administration. A sustained NUC released from NUC-PLGA-NPs with an initial exponential release owing to the surface associated drug followed by a slower release of NUC, which was entrapped in the core. In addition, ～77?±?6.67% was released in simulating intestinal juice, while only about 45.95?±?5.2% in simulating gastric juice. NUC-PLGA-NPs are more efficient against oleic acid (OA)-induced hepatic steatosis in HepG₂ cells when compared to naked NUC (n-NUC, *p < 0.05). The oral bioavailability of NUC-PLGA-NPs group was significantly higher (**p < 0.01) and a significantly decreased serum levels of total cholesterol (TC), triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C), as well as a higher concentration of high-density lipoprotein cholesterol (HDL-C) was observed, compared with that of n-NUC treated group. These findings suggest that NUC-PLGA-NPs hold great promise for sustained and controlled drug delivery with improved bioavailability to alleviating lipogenesis.     

Solid lipid nanoparticles for transdermal delivery of diclofenac sodium: preparation,characterization and in vitro studies

The aim of this study was to prepare diclofenac sodium (DNa) solid lipid nanoparticles (SLNs) by a modified emulsion/solvent evaporation method for transdermal delivery. Five independent processing parameters including the lipid matrix, emulsifiers, co-emulsifiers, water-dispersed phase and organic phase were assessed systematically to enhance the entrapment of DNa. The SLNs produced by optimal formulation were submicrometre size with low polydispersity index, the entrapment efficiency was about 89% and the drug loading was about 9.5%. Shape and surface morphology were determined by transmission electron microscopy, which revealed the fairly spherical and core-shell shapes of the SLNs. The in vitro release of SLNs showed a two-step release pattern: one initial burst release followed by a second slow-release phase. In the in vitro cutaneous permeation studies, value of flux obtained for DNa solution was higher than that of SLNs suspension. SLNs had also been shown to improve the dermal localization of DNa.     

GLP-1受体激动剂治疗2型糖尿病合并肾损伤患者的疗效和安全性:一项Meta分析

目的:评价胰高血糖素样肽-1受体激动剂(GLP-1RAs)在2型糖尿病(T2DM)合并肾损伤患者中的疗效和安全性,为该类药物的临床应用提供循证参考。方法:检索Medline、Embase、Cochrane Library、中国知网(CNKI)和万方数据库,查找有关GLP-1RAs治疗T2DM合并肾损伤患者的随机对照试验(RCT)。按照纳入与排除标准筛选文献,进行方法学质量评价之后提取相关资料,应用RevMan 5.3统计软件进行Meta分析。结果:最终纳入7项RCT,共计1 755例T2DM合并肾损伤患者。疗效方面,GLP-1RAs与胰岛素类似物或二肽基肽酶4抑制剂降低糖化血红蛋白的效应相当,但优于安慰剂,且该疗效在中重度肾损伤患者中比终末期肾病患者更佳;与对照组相比降低体质量[MD=－1.75,95% CI=(－2.18,－1.32),P<0.01]和降压作用[收缩压:MD=－7.79,95% CI=(－10.83,－4.74),P<0.01;舒张压:MD=－2.92,95% CI=(－4.79,－1.05),P=0.002]均有显著性差异;但降低空腹血糖和调节脂质代谢方面未见统计学差异。安全性方面,GLP-1RAs组与对照组致低血糖和肾损伤事件的发生率[RR=1.28,95% CI=(0.56,2.96),P=0.560;RR=0.85,95% CI=(0.44,1.62),P=0.620]无统计学差异,然而GLP-1RAs组胃肠道不良反应的发生率显著高于对照组(P<0.01)。结论:对于T2DM合并肾损伤患者,GLP-1RAs具有确切的降糖、减重和降压作用,而在终末期肾病患者中疗效降低;用药期间不增加低血糖和肾损伤风险,但应注意预防胃肠道不良反应的发生。     

Poly(lactic-co-glycolic acid) nanoparticles for sustained release of allyl isothiocyanate: characterization,in vitro release and biological activity

The objective of this study is to establish the ability of entrap allyl isothiocyanate (AITC) into polymeric nanoparticles to extend its shelf life and enhance its antiproliferative properties. Natural compounds, such as AITC, have showed multi-targeting activity resulting in a wide-range spectrum of therapeutic properties in chronic and degenerative diseases, conversely with most current pharmaceutical drugs showing single targeting activity and often result in drug resistance after extended administration periods. Apparently, AITC-loaded poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) reduced AITC degradation and volatility and were able to extend AITC shelf life compared with free AITC (65% vs. 20% in 24?h, respectively). Cell viability and uptake of AITC-loaded nanoparticles were studied in vitro, showing that the protection and sustained release of AITC from polymeric NPs involved a larger toxicity of tumoral cells. These nanoparticles could be used as protective systems for enhancing a biological activity.     

Preparation,characterization, and cytotoxic effects of liposomal nanoparticles containing cisplatin: an in vitro study

Cisplatin is a chemotherapeutic agent used for treating various malignancies. The study aimed to prepare pegylated liposomal cisplatin and evaluate its efficacy against human breast cancer cell line MCF‐7. Drug‐loaded nanoparticles were synthesized by reverse phase evaporation technique. The study is highlighted by extensive characterization of nanoparticles in terms of nanoparticle morphology, type of drug entrapment, cisplatin retention capability, and cytotoxicity effects. The size, size distribution, and zeta potential of nanodrug were estimated 142 nm, 0.33, and ?22 mV, respectively. Drug‐loading efficiency was equal to 48% that occurred physically. Furthermore, high retention capability (39% of drug was released after 72 h) with significantly enhanced cytotoxicity of nanodrug (1.75 times more than the standard drug) confirmed the potency of liposomal nanoparticles as proper cisplatin carrier.