Chitosan nanoparticles loaded with aspirin and 5‐fluororacil enable synergistic antitumour activity through the modulation of NF‐κB/COX‐2 signalling pathway

Based on the enhancement of synergistic antitumour activity to treat cancer and the correlation between inflammation and carcinogenesis, the authors designed chitosan nanoparticles for co‐delivery of 5‐fluororacil (5‐Fu: an as anti‐cancer drug) and aspirin (a non‐steroidal anti‐inflammatory drug) and induced synergistic antitumour activity through the modulation of the nuclear factor kappa B (NF‐κB)/cyclooxygenase‐2 (COX‐2) signalling pathways. The results showed that aspirin at non‐cytotoxic concentrations synergistically sensitised hepatocellular carcinoma cells to 5‐Fu in vitro. It demonstrated that aspirin inhibited NF‐κB activation and suppressed NF‐κB regulated COX‐2 expression and prostaglandin E2 (PGE2) synthesis. Furthermore, the proposed results clearly indicated that the combination of 5‐Fu and aspirin by chitosan nanoparticles enhanced the intracellular concentration of drugs and exerted synergistic growth inhibition and apoptosis induction on hepatocellular carcinoma cells by suppressing NF‐κB activation and inhibition of expression of COX‐2.Inspec keywords: proteins, molecular biophysics, cellular biophysics, biomedical materials, cancer, nanoparticles, drug delivery systems, enzymes, tumours, nanomedicine, drugsOther keywords: chitosan nanoparticles, aspirin, 5‐fluororacil, synergistic antitumour activity, anticancer drug, nonsteroidal antiinflammatory drug, hepatocellular carcinoma cells, NF‐κB activation, NF‐κB regulated COX‐2 expression, PGE2, synergistic growth inhibition, apoptosis induction, prostaglandin E2 synthesis, intracellular concentration, noncytotoxic concentrations, NF‐κB‐cyclooxygenase‐2 signalling pathways, cyclooxygenase‐2, nuclear factor kappa B     

Micro RNA‐30b (inhibitor) nanoparticles suppressed the lipopolysaccharide (LPS)‐induced acute kidney injury

The main aim of present study is to evaluate the effect of miR‐30b on the function of human proximal tubular epithelial cell line HK‐2 cells. For this purpose, miRNA was loaded in an ionically cross‐linked polysaccharide nanoparticle. The authors have demonstrated the influence of miR‐30b mimic and inhibitor in HK‐2 cell killing effect. Lipopolysaccharide (LPS) significantly increased the level of inflammatory cytokines of TNF‐α, IL‐1β and level was further increased with the treatment of PAg‐miR mimic consistent with the cell viability assay. Interestingly, PAg‐miR inhibitor significantly downregulated the expression of inflammatory cytokines and thereby reduced the inflammation in the body. Western blot analysis showed that LPS induced severe apoptosis of HK‐2 cells and the apoptosis was further promoted by the PAg‐miR (mimic). In contrast, PAg‐miR (inhibitor) alleviated the apoptosis of HK‐2 cells as indicated in the significantly reduced levels of Bax and c‐Caspase‐3 proteins. Overall, miR‐30b promoted LPS‐induced HK‐2 cell inflammatory injury by inducing the apoptosis and by releasing inflammatory cytokines, as well as by impairing autophagy process.Inspec keywords: biomedical materials, nanoparticles, molecular biophysics, enzymes, toxicology, injuries, nanomedicine, RNA, cellular biophysics, kidney, proteins, drugs, biochemistryOther keywords: microRNA‐30b, nanoparticles suppressed the lipopolysaccharide (LPS)‐induced, main aim, human proximal tubular epithelial cell line HK‐2 cells, polysaccharide nanoparticle, HK‐2 cell killing effect, inflammatory cytokines, IL‐1β, cell viability assay, PAg‐miR inhibitor, apoptosis, reduced levels, LPS‐induced HK‐2 cell inflammatory injury     

Sialic acid‐conjugated PLGA nanoparticles enhance the protective effect of lycopene in chemotherapeutic drug‐induced kidney injury

Lycopene (LYC) is known to protect cells from oxidative damage caused by free radicals in human tissues. In the present study, the authors designed a LYC‐loaded sialic acid (SA)‐conjugated poly(D,L‐lactide‐co‐glycolide) (PLGA) nanoparticle (LYC‐NP) to enhance the therapeutic efficacy of LYC in acute kidney injury. The characteristics of the LYC‐NPs were defined according to particle size, morphology, and in vitro drug release. The LYC‐NPs exhibited a controlled release of LYC over 48 h. Confocal laser scanning microscopy clearly highlighted the targeting potential of SA. Enhanced green fluorescence was observed for the LYC‐NPs in H₂ O₂ ‐treated human umbilical vein endothelial cells, indicating enhanced internalisation of NPs. The LYC‐NPs showed significantly greater cell viability than H₂ O₂ ‐treated cells. In addition, the LYC‐NPs remarkably reduced proinflammatory cytokine levels, attributable mainly to the increased cellular internalisation of the SA‐based carrier delivery system. Furthermore, protein levels of caspase‐3 and ‐9 were significantly down‐regulated after treatment with the LYC‐NPs. Overall, they have demonstrated that SA‐conjugated PLGA‐NPs containing LYC could be used to treat kidney injury.Inspec keywords: fluorescence, biomedical materials, biological tissues, cellular biophysics, drugs, proteins, molecular biophysics, injuries, drug delivery systems, kidney, nanomedicine, biochemistry, optical microscopy, nanoparticles, nanofabrication, cancer, toxicology, blood vessels, particle sizeOther keywords: sialic acid‐conjugated PLGA nanoparticles, chemotherapeutic drug‐induced kidney injury, LYC‐NP, LYC‐loaded sialic acid‐conjugated poly(D,L‐lactide‐co‐glycolide) nanoparticle, SA‐conjugated PLGA‐NP, protective effect, lycopene, human tissues, particle size, in vitro drug release, confocal laser scanning microscopy, green fluorescence, human umbilical vein endothelial cells, cell viability, proinflammatory cytokine levels, cellular internalisation, SA‐based carrier delivery system, time 48.0 hour     

Identification and analysis of circRNA–miRNA–mRNA regulatory network in hepatocellular carcinoma

This study was to identify important circRNA–miRNA–mRNA (ceRNAs) regulatory mechanisms in hepatocellular carcinoma (HCC). The circRNA dataset {"type":"entrez-geo","attrs":{"text":"GSE97332","term_id":"97332"}}GSE97332 and miRNA dataset {"type":"entrez-geo","attrs":{"text":"GSE57555","term_id":"57555"}}GSE57555 were used for analyses. Functional enrichment analysis for miRNA and target gene was conducted using cluster Profiler. Survival analysis was conducted through R package Survival. The ceRNAs and drug–gene interaction networks were constructed. The ceRNAs network contained five miRNAs including hsa‐miR‐25‐3p, hsa‐miR‐3692‐5p, hsa‐miR‐4270, hsa‐miR‐331‐3p, and hsa‐miR‐125a‐3p. Among the network, hsa‐miR‐25‐3p targeted the most genes, hsa‐miR‐3692‐5p and hsa‐miR‐4270 were targeted by more circRNAs than other miRNAs, hsa‐circ‐0034326 and hsa‐circ‐0011950 interacted with three miRNAs. Furthermore, target genes, including NRAS, ITGA5, SLC7A1, SEC14L2, SLC12A5, and SMAD2 were obtained in drug–gene interaction network. Survival analysis showed NRAS, ITGA5, SLC7A1, SEC14L2, SLC12A5, and SMAD2 were significantly associated with prognosis of HCC. NRAS, ITGA5, and SMAD2 were significantly enriched in proteoglycans in cancer. Moreover, hsa‐circ‐0034326 and hsa‐circ‐0011950 might function as ceRNAs to play key roles in HCC. Furthermore, miR‐25‐3p, miR‐3692‐5p, and miR‐4270 might be significant for HCC development. NRAS, ITGA5, SEC14L2, SLC12A5, and SMAD2 might be prognostic factors for HCC patients via proteoglycans in cancer pathway. Taken together, the findings will provide novel insight into pathogenesis, selection of therapeutic targets and prognostic factors for HCC.Inspec keywords: cancer, cellular biophysics, patient diagnosis, bioinformatics, tumours, biochemistry, molecular biophysics, genetics, drugs, RNAOther keywords: ITGA5, SMAD2, hsa‐circ‐0034326, SEC14L2, SLC12A5, target gene, survival analysis, drug–gene interaction network, miRNAs, hsa‐miR‐25‐3p, hsa‐miR‐3692‐5p, hsa‐miR‐4270, hsa‐miR‐331‐3p, hsa‐miR‐125a‐3p, hsa‐circ‐0011950, SLC7A1, pathogenesis, therapeutic targets, prognostic factors, circRNA‐miRNA‐mRNA regulatory network, current 125.0 A     

Investigation of chitosan‐g‐PEG grafted nanoparticles as a half‐life enhancer carrier for tissue plasminogen activator delivery

Tissue plasminogen activator (tPA) a thrombolytic agent is commonly used for digesting the blood clot. tPA half‐life is low (4–6 min) and its administration needs a prolonged continuous infusion. Improving tPA half‐life could reduce enzyme dosage and enhance patient compliance. Nano‐carries could be used as delivery systems for the protection of enzymes physically, enhancing half‐life and increasing the stability of them. In this study, chitosan (CS) and polyethylene glycol (PEG) were used for the preparation of CS‐g‐PEG/tPA nanoparticles (NPs) via the ion gelation method. Particles’ size and loading capacity were optimised by central composite design. Then, NPs cytotoxicity, release profile, enzyme activity and in vivo half‐life and coagulation time were investigated. The results showed that NPs does not have significant cytotoxicity. Release study revealed that a burst effect happened in the first 5 min and resulted in releasing 30% of tPA. Loading tPA in NPs could decrease 25% of its activity but the half‐life of it increases in comparison to free tPA in vivo. Also, blood coagulation time has significantly affected (p ‐value = 0.041) by encapsulated tPA in comparison to free tPA. So, CS‐g‐PEG/tPA could increase enzyme half‐life during the time and could be used as a non‐toxic candidate delivery system for tPA.Inspec keywords: drug delivery systems, nanofabrication, drugs, nanomedicine, coagulation, biomedical materials, cellular biophysics, enzymes, biochemistry, toxicology, molecular biophysics, biological tissues, blood, nanoparticles, polymersOther keywords: chitosan‐g‐PEG grafted nanoparticles, half‐life enhancer carrier, tissue plasminogen activator delivery, tPA half‐life, prolonged continuous infusion, enzyme dosage, polyethylene glycol, cytotoxicity, enzyme activity, encapsulated tPA, enzyme half‐life, blood coagulation, time 5.0 min     

Dioscin‐loaded zein nanoparticles alleviate lipopolysaccharide‐induced acute kidney injury via the microRNA‐let 7i signalling pathways

The present study investigates the potential role of dioscin (DIO) in the lipopolysaccharide (LPS)‐induced kidney injury. For this purpose, DIO‐loaded zein nanoparticles (DIO‐ZNPs) were formulated and evaluated for physicochemical parameters. The DIO‐ZNPs exhibited a controlled release of drug compared with that of the free drug suspension. Results showed that the cell viability of NRK‐52E consistently decreased with the increase in LPS from 0.01 µg/ml to 2 µg/ml. When compared with LPS, DIO‐induced NPs showed 1.10‐, 1.32‐, 1.57‐ and 1.92‐fold increase in the cell viability for concentrations of 20 µg/ml, 50 µg/ml, 100 µg/ml and 200 µg/ml, respectively. DIO‐ZNPs exhibited the most remarkable recovery in the cell proliferation compared with free DIO as shown by the cellular morphology analysis. Furthermore, Annexin‐V staining analysis showed that the LPS‐treated cells possess the lowest green fluorescence indicating fewer viable cells, whereas DIO‐ZNPs exhibited the maximum green fluorescence comparable with that of the non‐treated cells indicating maximum cell viability. Furthermore, the results show that DIO‐ZNPs significantly increased the expression of miR‐let‐7i in the epithelial kidney cells, whereas the expression levels of TLR4 were significantly downregulated compared with that of the LPS‐treated cells. In conclusion, miR‐let‐7i could be an interesting therapeutic target and nanoparticle‐based DIO could be a potential candidate in the management of acute kidney injuryInspec     

Multi‐threshold and multi‐input DNA logic design style for profiling the microRNA biomarkers of real cancers

Early detection of cancer is very critical because it can reduce the treatment risk and cost. MicroRNAs (miRNAs) have been introduced in recent years as an efficient class of biomarkers for cancer early detection. Now, real‐time polymerase chain reaction has been used to profile the miRNA expression, which is costly, time consuming and low accuracy. Most recently, DNA logic gates are used to detect the miRNA expression level that is more accurate and faster than previous methods. The DNA‐based logic gates face with serious challenges such as the large complexity and low scalability. In this study, the authors proposed a methodology to design multi‐threshold and multi‐input DNA‐based logic gates in response to specific miRNA inputs in live mammalian cells. The proposed design style can simultaneously recognise multiple miRNAs with different rising and falling thresholds. The design style has been evaluated on the lung cancer biomarkers and the experimental results show the efficiency of the proposed method in terms of accuracy, efficiency and speed.Inspec keywords: DNA, logic design, biocomputing, RNA, molecular biophysics, logic gates, lung, genetics, cellular biophysics, cancer, biology computing, enzymes, biosensorsOther keywords: falling thresholds, specific miRNA inputs, multiinput DNA‐based logic gates, low scalability, DNA‐based logic gates face, miRNA expression level, DNA logic gates, low accuracy, time consuming, real‐time polymerase chain reaction, cancer early detection, treatment risk, cancers, microRNA biomarkers, multiinput DNA logic design style, multithreshold, lung cancer biomarkers     

Nano‐encapsulated Tinospora cordifolia (Willd.) using poly (D,L‐lactide) nanoparticles educe effective control in streptozotocin‐induced type 2 diabetic rats

The therapeutics for type 2 diabetes mellitus has emerged in the current century towards nanomedicine incorporated with plant active compounds. In this study, Tinospora cordifolia loaded poly (D, L‐lactide) (PLA) nanoparticles (NPs) were evaluated in vivo for their anti‐hyperglycemic potency towards streptozotocin‐induced type 2 diabetic rats. T. cordifolia loaded PLA NPs were synthesised by the double solvent evaporation method using PLA polymer. The NPs were then characterised and administrated orally for 28 successive days to streptozotocin‐induced diabetic rats. The PLA NPs had significant anti‐diabetic effects which were equal to the existing anti‐diabetic drug glibenclamide. The antidiabetic activity is due to the synergism of compounds present in stem extract of the plant which reduced the side effects and anti‐diabetic.Inspec keywords: blood, nanofabrication, drug delivery systems, biochemistry, evaporation, nanoparticles, nanomedicine, drugs, diseases, polymers, biomedical materialsOther keywords: PLA nanoparticles, antidiabetic effects, nanoencapsulated Tinospora cordifolia, streptozotocin‐induced type 2 diabetic rats, type 2 diabetes mellitus, poly(d, l‐lactide) nanoparticles, diabetic drug glibenclamide, nanomedicine, antihyperglycemic potency, double‐solvent evaporation     

Cross‐linking gold nanoparticles aggregation method based on localised surface plasmon resonance for quantitative detection of miR‐155

MiR‐155 plays a critical role in the formation of cancers and other diseases. In this study, the authors aimed to design and fabricate a biosensor based on cross‐linking gold nanoparticles (AuNPs) aggregation for the detection and quantification of miR‐155. Also, they intended to compare this method with SYBR Green real‐time polymerase chain reaction (PCR). Primers for real‐time PCR, and two thiolated capture probes for biosensor, complementary with miR‐155, were designed. Citrate capped AuNPs (18.7 ± 3.6 nm) were synthesised and thiolated capture probes immobilised to AuNPs. The various concentrations of synthetic miR‐155 were measured by this biosensor and real‐time PCR method. Colorimetric changes were studied, and the calibration curves were plotted. Results showed the detection limit of 10 nM for the fabricated biosensor and real‐time PCR. Also, eye detection using colour showed the weaker detection limit (1 µM), for this biosensor. MiR‐133b as the non‐complementary target could not cause a change in both colour and UV–visible spectrum. The increase in hydrodynamic diameter and negative zeta potential of AuNPs after the addition of probes verified the biosensor accurately fabricated. This fabricated biosensor could detect miR‐155 simpler and faster than previous methods.Inspec keywords: RNA, molecular biophysics, biochemistry, cancer, nanoparticles, gold, aggregation, surface plasmon resonance, molecular configurations, nanosensors, enzymes, calibration, ultraviolet spectra, visible spectra, eye, hydrodynamics, electrokinetic effects, biosensors, nanofabricationOther keywords: cross‐linking gold nanoparticles aggregation method, localised surface plasmon resonance, quantitative detection, cancers, diseases, biosensor, miR‐155 detection, miR‐155 quantification, SYBR green real‐time polymerase chain reaction, thiolated capture probes, citrate capped AuNPs, synthetic miR‐155, real‐time PCR method, colorimetric changes, calibration curves, eye detection, colour, detection limit, MiR‐133b, noncomplementary target, UV‐visible spectrum, hydrodynamic diameter, negative zeta potential, Au     

Sustained delivery of olanzapine from sunflower oil‐based polyol‐urethane nanoparticles synthesised through a cyclic carbonate ring‐opening reaction

The forefront horizon of biomedical investigations in recent decades is parcelling‐up and delivery of drugs to achieve controlled/targeted release. In this regard, developing green‐based delivery systems for a spatiotemporal controlling therapeutic agent have drawn a lot of attention. A facile route based on cyclic carbonate ring‐opening reaction has been utilised to synthesise a bio‐based polyol‐containing urethane bond [polyol‐urethane (POU)] as a nanoparticulate drug delivery system of olanzapine in order to enhance its bioavailability. After characterisation, the nanoparticles were also estimated for in vitro release, toxicity, and pharmacokinetic studies. As olanzapine has shown poor bioavailability and permeability in the brain, the sustained release of olanzapine from the designed carriers could enhance pharmacokinetic effectiveness. POU in the aqueous solution formed micelles with a hydrophobic core and embedded olanzapine under the influence of its hydrophobic nature. Drug release from the nanoparticles (90 ± 0.43 nm in diameter) indicated a specific pattern with initial burst release, and then a sustained release behaviour (82 ± 3% after 168 h), by the Higuchi‐based release mechanism. Pharmacokinetics assessments of POU‐olanzapine nanoparticles were carried in male Wistar rats through intravenous administration. The obtained results paved a way to introduce the POU as an efficient platform to enhance the bioavailability of olanzapine in therapeutic methods.Inspec keywords: hydrophobicity, nanomedicine, nanofabrication, nanoparticles, drug delivery systems, biomedical materials, polymers, brainOther keywords: cyclic carbonate ring‐opening reaction, nanoparticulate drug delivery system, bioavailability, drug release, initial burst release, Higuchi‐based release mechanism, POU‐olanzapine nanoparticles, sunflower oil‐based polyol‐urethane nanoparticles, forefront horizon, biomedical investigations, green‐based delivery systems, spatiotemporal controlling therapeutic agent, bio‐based polyol‐containing urethane bond, polyol‐urethane, toxicity, pharmacokinetic studies, olanzapine, aqueous solution, micelles, hydrophobic core, Pharmacokinetics, male Wistar rats, brain     

Development of tamoxifen‐loaded surface‐modified nanostructured lipid carrier using experimental design: in vitro and ex vivo characterisation

The present study aimed to develop a surface‐modified biocompatible nanostructured lipid carrier (NLCs) system using polyoxyethylene (40) stearate (POE‐40‐S) to improve the oral bioavailability of poorly water‐soluble Biopharmaceutics Classification System class‐II drug like tamoxifen (TMX). Also aimed to screen the most influential factors affecting the particle size (PS) using Taguchi (L₁₂ (2¹¹)) orthogonal array design (TgL₁₂ OA). Then, to optimize the TMX loaded POE‐40‐S (P) surface‐modified NLCs (TMX‐loaded‐PEG‐40‐S coated NLC (PNLCs) or PNLCs) by central composite design (CCD) using a four‐factor, five‐level model. The most influential factors affecting the PS was screened and optimized. The in‐vitro study showed that increased drug‐loading (DL) and encapsulation efficiency (EE), decreased PS and charge, sustained drug release for the prolonged period of the time with good stability and suppressed protein adsorption. The Ex‐vivo study showed that decreased mucous binding with five‐fold enhanced permeability of PNLC formulation after surface modification with POE‐40‐S. The in‐vitro cytotoxicity study showed that the blank carrier is biocompatible and cytotoxicity of the formulation was dependent on the concentration of the drug. Finally, it can be concluded that the surface‐modified PNLCs formulation was an effective, biocompatible, stable formulation in the enhancement of dissolution rate, solubility, stability with reduced mucus adhesion and increased permeability thereby which indicates its enhanced oral bioavailability.Inspec keywords: nanoparticles, cellular biophysics, solubility, drug delivery systems, toxicology, adsorption, adhesion, dissolving, biomedical materials, encapsulation, polymers, proteins, nanomedicine, permeability, particle size, electrokinetic effectsOther keywords: water‐soluble BCS class‐II, TgL₁₂ OA, TMX‐loaded POE‐40‐S surface‐modified NLC, surface‐modified PNLC formulation, lipid‐based NLC system, oral bioavailability, stable formulation, biocompatible formulation, blank carrier, in vitro cytotoxicity, surface modification, PNLC formulation, drug release, central composite design, orthogonal array design, encapsulation efficiency, steric stabilisation effect, particle size, dissolution rate, polyoxyethylene stearate, surface‐modified biocompatible carrier system, systemic toxicity, water‐soluble drug, tamoxifen‐loaded surface‐modified nanostructured lipid carrier     

MicroRNAs and their target mRNAs as potential biomarkers among smokers and non‐smokers with lung adenocarcinoma

Lung adenocarcinoma is one of the major causes of mortality. Current methods of diagnosis can be improved through identification of disease specific biomarkers. MicroRNAs are small non‐coding regulators of gene expression, which can be potential biomarkers in various diseases. Thus, the main objective of this study was to gain mechanistic insights into genetic abnormalities occurring in lung adenocarcinoma by implementing an integrative analysis of miRNAs and mRNAs expression profiles in the case of both smokers and non‐smokers. Differential expression was analysed by comparing publicly available lung adenocarcinoma samples with controls. Furthermore, weighted gene co‐expression network analysis is performed which revealed mRNAs and miRNAs significantly correlated with lung adenocarcinoma. Moreover, an integrative analysis resulted in identification of several miRNA–mRNA pairs which were significantly dysregulated in non‐smokers with lung adenocarcinoma. Also two pairs (miR‐133b/Protein Kinase C Zeta (PRKCZ) and miR‐557/STEAP3) were found specifically dysregulated in smokers. Pathway analysis further revealed their role in important signalling pathways including cell cycle. This analysis has not only increased the authors’ understanding about lung adenocarcinoma but also proposed potential biomarkers. However, further wet laboratory studies are required for the validation of these potential biomarkers which can be used to diagnose lung adenocarcinoma.Inspec keywords: cancer, molecular biophysics, patient diagnosis, tumours, RNA, proteins, lung, genetics, medical diagnostic computing, molecular configurationsOther keywords: miRNAs expression profiles, mRNAs expression profiles, smokers, nonsmokers, integrative analysis, lung adenocarcinoma, microRNAs, disease specific biomarkers, noncoding regulators, genetic abnormalities, weighted gene coexpression network analysis     

HER‐2 aptamer‐targeted Ecoflex® nanoparticles loaded with docetaxel promote breast cancer cells apoptosis and anti‐metastatic effect

Breast cancer is a major cause of cancer mortality. Regarding the advantages of polymeric nanoparticles as drug delivery systems with targeting potential, in this study the antitumor mechanism of targeted docetaxel polymeric nanoparticles of Ecoflex^® was exploited. Since the overexpression of HER‐2 receptor in breast cancer cases is associated with poor prognosis and more aggressive disease, the proposed nanoparticles were conjugated to HER‐2 specific aptamer molecules. In vitro cytotoxicity was evaluated by MTT assay. Flow‐cytometry analysis was performed to evaluate the cellular uptake of nanoparticles loaded with a fluorescent probe. Anti‐migration effects of samples were studied. Annexin IV‐FITC and propidium iodide were implemented to investigate apoptosis induction and cell cycle analysis. Enhanced cytotoxicity compared with free docetaxel was explained considering improved cellular uptake of the nanoparticles and induced apoptosis in a larger portion of cells. Lower relative migration demonstrated enhanced anti‐migration effect of nanoparticles, and cell cycle was arrested in G2/M phase using both formulations so the anti‐microtubule mechanism of the drug was not altered. Therefore, this system could offer a potential substitute for the currently marketed docetaxel formulations, which may reduce adverse effects of the drug, while further in vivo and clinical investigations are required.Inspec keywords: cancer, molecular biophysics, drug delivery systems, fluorescence, biomedical materials, drugs, tumours, nanomedicine, proteins, toxicology, biochemistry, nanoparticles, diseases, cell motility, polymersOther keywords: antitumor mechanism, targeted docetaxel polymeric nanoparticles, HER‐2 specific aptamer molecules, MTT assay, flow‐cytometry analysis, annexin IV‐FITC, apoptosis induction, cell cycle, lower relative migration, cancer mortality, drug delivery systems, aggressive disease, in vitro cytotoxicity, cellular uptake, breast cancer cell apoptosis, antimetastatic effect, HER‐2 aptamer‐targeted Ecoflex nanoparticles, antimigration effect, antimicrotubule mechanism, HER‐2 receptor, fluorescent probe, propidium iodide     

In‐vitro and in‐vivo evaluation of chitosan‐based thermosensitive gel containing lorazepam NLCs for the treatment of status epilepticus

The objective of this study was to develop an in‐situ gel containing lorazepam (LZM) loaded nanostructured lipid carriers (NLCs) for direct nose‐to‐brain delivery in order to increase drug therapeutic efficacy in the treatment of epilepsy. Accordingly, LZM loaded NLCs were formulated using emulsification solvent diffusion and evaporation method; then the effects of the formulation variables on different physicochemical characteristics of NLCs were investigated. Thermosensitive in‐situ gels containing LZM‐NLCs were prepared using a combination of chitosan and β‐glycerol phosphate (β‐GP). The anticonvulsant efficacy of LZM‐NLCs‐Gel was then examined using the pentylenetetrazole (PTZ) model. The optimised NLCs were spherical, showing the particle size of 71.70 ± 5.16 nm and the zeta potential of −20.06 ± 2.70 mV. The pH and gelation time for the chitosan solution with 15% (w/v) β‐GP were determined to be 7.12 ± 0.03 and 5.33 ± 0.58 min, respectively. The in‐vivo findings showed that compared with the control group and the group that received LZM‐Gel, the occurrence of PTZ‐induced seizures in the rats was significantly reduced by LZM‐NLCs‐Gel after intranasal administration. These results, therefore, suggested that the LZM‐NLCs‐Gel system could have potential applications for brain targeting through nasal route and might increase LZM therapeutic efficacy in the treatment of epilepsy.Inspec keywords: biomedical materials, nanomedicine, cellular biophysics, electrokinetic effects, drug delivery systems, nanoparticles, brain, pH, drugs, particle size, nanofabrication, medical disorders, polymer gelsOther keywords: evaporation method, β‐glycerol phosphate, β‐GP, optimised NLCs, received LZM‐Gel, LZM therapeutic efficacy, chitosan‐based thermosensitive gel, lorazepam NLCs, nose‐to‐brain delivery, drug therapeutic efficacy, emulsification solvent diffusion, in‐vivo evaluation, in‐vitro evaluation, LZM‐NLC‐gel system, status epilepticus treatment, lorazepam loaded nanostructured lipid carriers, epilepsy treatment, physicochemical characteristics, thermosensitive in‐situ gel, anticonvulsant efficacy, pentylenetetrazole model, particle size, zeta potential, pH, gelation time, chitosan solution, PTZ‐induced seizures, intranasal administration     

Synthesis of surfactant‐modified ZIF‐8 with controllable microstructures and their drug loading and sustained release behaviour

Metal‐organic frameworks (MOFs) as drug carriers have many advantages than traditional drug carriers and have received extensive attention from researchers. However, how to regulate the microstructure of MOFs to improve the efficiency of drug delivery and sustained release behaviour is still a big problem for the clinical application. Herein, the authors synthesise surfactant‐modified ZIF‐8 nanoparticles with different microstructures by using different types of surfactants to modify ZIF‐8. The surfactant‐modified ZIF‐8 nanoparticles have the larger specific surface area and total micropore volumes than the original ZIF‐8, which enables doxorubicin (DOX) to be more effectively loaded on the drug carriers and achieve controlled drug sustained release. Excellent degradation performance of ZIF‐8 nanoparticles facilitates the metabolism of drug carriers. The formulation was evaluated for cytotoxicity, cellular uptake and intracellular location in the A549 human non‐small‐cell lung cancer cell line. ZIF‐8/DOX nano drugs exhibit higher cytotoxicity towards cells in comparison with free DOX, suggesting the potential application in nano drugs to cancer chemotherapy.Inspec keywords: nanomedicine, lung, nanofabrication, drug delivery systems, cellular biophysics, nanoparticles, cancer, toxicology, biomedical materials, drugs, organometallic compounds, surfactants, porosity, biodegradable materialsOther keywords: controlled drug sustained release, nanodrugs, controllable microstructures, drug loading, metal‐organic frameworks, traditional drug carriers, drug delivery, surfactant‐modified ZIF‐8 nanoparticles, specific surface area, micropore volumes, doxorubicin, degradation performance, metabolism, cytotoxicity, cellular uptake, intracellular location, A549 human nonsmall‐cell lung cancer cell line, cancer chemotherapy     

Facile synthesis of mesoporous alumina using hexadecyltrimethylammonium bromide (HTAB) as template: simplified sol‐gel approach

Herein the authors present the synthesis of surface functionalised mesoporous alumina (MeAl) for textural characterisation by a simplified sol–gel method obtained by using hexadecyltrimethylammonium bromide as a template. Etoricoxib (ETOX) was used as a model drug for the study. Alumina supported mesoporous material containing drug was characterised using instrumental technique namely Brunauer–Emmett–Teller surface area, Fourier transform‐infrared, differential scanning calorimetry, transmission electron microscopy, X‐ray diffraction, and field emission scanning electron microscopy. Diffusion study using a dialysis bag method used to check the release pattern of ETOX‐loaded‐MeAl. Results of characterisation study revealed the successful surface functionalisation of the drug on nanocomposite. The IC₅₀ value obtained from cell viability study demonstrated the non‐toxic behaviour of synthesised drug‐loaded mesoporous alumina up to the tested concentration range. The present work has demonstrated that synthesised MeAl showed excellent stability with an expanded surface area suitable for carrier material for drug delivery system.Inspec keywords: Fourier transform spectra, adsorption, biomedical materials, silicon compounds, drug delivery systems, X‐ray diffraction, alumina, differential scanning calorimetry, nanocomposites, field emission electron microscopy, nanofabrication, nanomedicine, mesoporous materials, transmission electron microscopy, sol‐gel processing, scanning electron microscopyOther keywords: ETOX‐loaded‐MeAl, successful surface functionalisation, synthesised drug‐loaded mesoporous alumina, synthesised MeAl, expanded surface area, drug delivery system, hexadecyltrimethylammonium bromide, sol‐gel approach, surface functionalised mesoporous alumina, simplified sol–gel method, mesoporous material containing drug, Brunauer–Emmett–Teller surface area, Fourier transform‐infrared, differential scanning calorimetry, transmission electron microscopy, X‐ray diffraction, field emission scanning electron microscopy, dialysis bag method     

Redox/pH dual stimuli‐responsive ZnO QDs‐gated mesoporous silica nanoparticles as carriers in cancer therapy

New drug delivery system (ZnO@CMS) of the redox and pH dual‐stimuli responsive based on colloidal mesoporous silica nanoparticles (CMS) has been designed, in which zinc oxide quantum dots (ZnO QDs) as a capping agent was conjugated on the surface of nanoparticles by amide bonds. The release behaviour of doxorubicin (DOX) as the model drug from ZnO@CMS (ZnO@CMS‐DOX) indicated the redox and pH dual‐stimuli responsive properties due to the acidic dissolution of ZnO QDs and cleavage of the disulphide bonds. The haemolysis and bovine serum albumin adsorption assays showed that the modification of ZnO QDs on the mesoporous silica nanoparticles modified by mercapto groups (CMS‐SH)(ZnO@CMS) had better biocompatibility compared to CMS‐SH. The cell viability and cellular uptake tests revealed that the ZnO@CMS might achieve the antitumour effect on cancer cells due to the cytotoxicity of ZnO QDs. Therefore, ZnO@CMS might be potential nanocarriers of the drug delivery system in cancer therapy. The in vivo evaluation of ZnO@CMS would be carried out in future work.Inspec keywords: biochemistry, nanomedicine, cellular biophysics, pH, toxicology, tumours, semiconductor quantum dots, proteins, colloids, II‐VI semiconductors, mesoporous materials, silicon compounds, oxidation, cancer, drug delivery systems, zinc compounds, adsorption, molecular biophysics, nanomagnetics, drugs, biomedical materials, nanofabrication, nanoparticles, nanoporous materialsOther keywords: cancer therapy, drug delivery system, amide bonds, haemolysis, bovine serum albumin adsorption assays, mercapto groups, cancer cells, cytotoxicity, antitumour effect, redox/pH dual stimuli‐responsive zinc oxide quantum dots‐gated colloidal mesoporous silica nanoparticles, ZnO, SiO₂      

Trastuzumab‐conjugated nanoparticles composed of poly(butylene adipate‐co ‐butylene terephthalate) prepared by electrospraying technique for targeted delivery of docetaxel

Human epidermal growth factor receptor 2 (HER‐2) is overexpressed in 20–30% of human breast cancers, associated with poor prognosis and tumour aggression. The aim of this study was the production of trastuzumab‐targeted Ecoflex nanoparticles (NPs) loaded with docetaxel and in vitro evaluation of their cytotoxicity and cellular uptake. The NPs were manufactured by electrospraying and characterised regarding size, zeta potential, drug loading, and release behaviour. Then their cytotoxicity was evaluated by MTT assay against an HER‐2‐positive cell line, BT‐474, and an HER‐2‐negative cell line, MDA‐MB‐468. The cellular uptake was studied by flow cytometry and fluorescent microscope. The particle size of NPs was in an appropriate range, with relatively high drug entrapment and acceptable release efficiency. The results showed no cytotoxicity for the polymer, but the significant increment of cytotoxicity was observed by treatment with docetaxel‐loaded NPs in both HER‐2‐positive and HER‐2‐negative cell lines, in comparison with the free drug. The trastuzumab‐targeted NPs also significantly enhanced cytotoxicity against BT‐474 cells, compared with non‐targeted NPs.Inspec keywords: cancer, proteins, biomedical materials, nanofabrication, drug delivery systems, cellular biophysics, biological organs, nanomedicine, toxicology, tumours, nanoparticles, biomedical optical imaging, fluorescence, particle sizeOther keywords: human breast cancers, tumour aggression, trastuzumab‐targeted Ecoflex nanoparticles, cellular uptake, zeta potential drug loading, HER‐2‐positive cell line, HER‐2‐negative cell line, MDA‐MB‐468, particle size, trastuzumab‐conjugated nanoparticles, electrospraying technique, human epidermal growth factor receptor, cytotoxicity, nontargeted nanoparticles, butylene adipate‐co‐butylene terephthalate, trastuzumab‐targeted NP, docetaxel‐loaded NP