Efavirenz oral delivery via lipid nanocapsules: formulation,optimisation, and ex‐vivo gut permeation study

Present investigation aimed to prepare, optimise, and characterise lipid nanocapsules (LNCs) for improving the solubility and bioavailability of efavirenz (EFV). EFV‐loaded LNCs were prepared by the phase‐inversion temperature method and the influence of various formulation variables was assessed using Box–Behnken design. The prepared formulations were characterised for particle size, polydispersity index (PdI), zeta potential, encapsulation efficiency (EE), and release efficiency (RE). The biocompatibility of optimised formulation on Caco‐2 cells was determined using 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5‐diphenyltetrazolium bromide assay. Then, it was subjected to ex‐vivo permeation using rat intestine. EFV‐loaded LNCs were found to be spherical shape in the range of 20–100 nm with EE of 82–97%. The best results obtained from LNCs prepared by 17.5% labrafac and 10% solutol HS15 when the volume ratio of the diluting aqueous phase to the initial emulsion was 3.5. The mean particle size, zeta potential, PdI, EE, drug loading%, and RE during 144 h of optimised formulation were confirmed to 60.71 nm, −35.93 mV, 0.09, 92.60, 7.39 and 55.96%, respectively. Optimised LNCs increased the ex vivo intestinal permeation of EFV when compared with drug suspension. Thus, LNCs could be promising for improved oral delivery of EFV.Inspec keywords: biomedical materials, solubility, drugs, encapsulation, emulsions, nanoparticles, particle size, nanofabrication, suspensions, toxicology, nanomedicine, cellular biophysics, lipid bilayers, electrokinetic effects, drug delivery systems, molecular biophysicsOther keywords: ex‐vivo permeation, diluting aqueous phase, mean particle size, zeta potential, drug loading, optimised formulation, ex vivo intestinal permeation, improved oral delivery, efavirenz oral delivery, optimisation, ex‐vivo gut permeation study, solubility, bioavailability, phase‐inversion temperature method, formulation variables, Box–Behnken design, polydispersity index, encapsulation efficiency, Caco‐2 cells, lipid nanocapsules, 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5‐diphenyltetrazolium bromide assay, EFV‐loaded LNC, drug suspension, size 20.0 nm to 100.0 nm, time 144.0 hour, size 60.71 nm, voltage ‐35.93 mV     

Fabrication and characterisation of super‐paramagnetic responsive PLGA–gelatine–magnetite scaffolds with the unidirectional porous structure: a physicochemical,mechanical, and in vitro evaluation

Architecture and composition of Scaffolds are influential factors in the regeneration of defects. Herein, synthesised iron oxide (magnetite) nanoparticles (MNPs) by co‐precipitation technique were evenly distributed in polylactic‐co‐glycolic acid (PLGA)–gelatine Scaffolds. Hybrid structures were fabricated by freeze‐casting method to the creation of a matrix with tunable pores. The synthesised MNPs were characterised by transmission electron microscopy, Fourier transform infrared spectroscopy, X‐ray diffraction spectroscopy, and vibrating sample magnetometer analysis. Scanning electron microscopy micrographs of porous Scaffolds confirmed the formation of unidirectional microstructure, so that pore size measurement indicated the orientation of pores in the direction of solvent solidification. The addition of MNPs to the PLGA–gelatine Scaffolds had no particular effect on the morphology of the pores, but reduced slightly pore size distribution. The MNPs contained constructs demonstrated increased mechanical strength, but a reduced absorption capacity and biodegradation ratio. Stability of the MNPs and lack of iron release was the point of strength in this investigation and were determined by atomic absorption spectroscopy. The evolution of rat bone marrow mesenchymal stem cells performance on the hybrid structure under a static magnetic field indicated the potential of super‐paramagnetic constructs for further pre‐clinical and clinical studies in the field of neural regeneration.Inspec keywords: transmission electron microscopy, biodegradable materials, nanofabrication, freezing, mechanical strength, tissue engineering, X‐ray diffraction, cellular biophysics, precipitation (physical chemistry), biomedical materials, iron compounds, porosity, scanning electron microscopy, atomic absorption spectroscopy, gelatin, nanoparticles, porous materials, bone, nanocomposites, Fourier transform infrared spectraOther keywords: unidirectional microstructure, pore size measurement, mechanical strength, atomic absorption spectroscopy, hybrid structure, super‐paramagnetic responsive PLGA–gelatine–magnetite scaffolds, unidirectional porous structure, tissue engineering Scaffolds, co‐precipitation technique, polylactic‐co‐glycolic acid–gelatine Scaffolds, freeze‐casting method, transmission electron microscopy, Fourier‐transform infrared spectroscopy, X‐ray diffraction spectroscopy, scanning electron microscopy micrographs, pore size distribution, absorption capacity, iron oxide nanoparticles, Fe₃ O₄      

Luteinizing hormone‐releasing hormone targeted poly(methyl vinyl ether maleic acid) nanoparticles for doxorubicin delivery to MCF‐7 breast cancer cells

The purpose of this study was to design a targeted anti‐cancer drug delivery system for breast cancer. Therefore, doxorubicin (DOX) loaded poly(methyl vinyl ether maleic acid) nanoparticles (NPs) were prepared by ionic cross‐linking method using Zn²⁺ ions. To optimise the effect of DOX/polymer ratio, Zn/polymer ratio, and stirrer rate a full factorial design was used and their effects on particle size, zeta potential, loading efficiency (LE, %), and release efficiency in 72 h (RE₇₂, %) were studied. Targeted NPs were prepared by chemical coating of tiptorelin/polyallylamin conjugate on the surface of NPs by using 1‐ethyl‐3‐(3‐dimethylaminopropyl) carboiimid HCl as cross‐linking agent. Conjugation efficiency was measured by Bradford assay. Conjugated triptorelin and targeted NPs were studied by Fourier‐transform infrared spectroscopy (FTIR). The cytotoxicity of DOX loaded in targeted NPs and non‐targeted ones were studied on MCF‐7 cells which overexpress luteinizing hormone‐releasing hormone (LHRH) receptors and SKOV3 cells as negative LHRH receptors using Thiazolyl blue tetrazolium bromide assay. The best results obtained from NPs prepared by DOX/polymer ratio of 5%, Zn/polymer ratio of 50%, and stirrer rate of 960 rpm. FTIR spectrum confirmed successful conjugation of triptorelin to NPs. The conjugation efficiency was about 70%. The targeted NPs showed significantly less IC₅₀ for MCF‐7 cells compared to free DOX and non‐targeted NPs.Inspec keywords: nanoparticles, polymer blends, cancer, cellular biophysics, drug delivery systems, drugs, biomedical materials, zinc, positive ions, Fourier transform infrared spectra, nanomedicine, proteinsOther keywords: luteinizing hormone‐releasing hormone, poly(methyl vinyl ether maleic acid), doxorubicin delivery, MCF‐7 breast cancer cell, anticancer drug delivery system, doxorubicin‐loaded PVM‐MA nanoparticle, ionic cross‐linking method, zinc ion, doxorubicin‐polymer ratio effect, zinc‐polymer ratio effect, particle size, zeta potential, loading efficiency, release efficiency, chemical coating, tiptorelin‐polyallylamin conjugation, PVM‐MA nanoparticle surface, 1‐ethyl‐3‐(3‐dimethylaminopropyl) carboiimid HCl, cross‐linking agent, Bradford assay, Fourier transform infrared spectroscopy, cytotoxicity, LHRH receptor, SKOV3 cell, Thiazolyl blue tetrazolium bromide assay, conjugation efficiency, time 72 h, Zn²⁺      

Preparation and in vitro evaluation of novel cross‐linked chondroitin sulphate nanoparticles by aluminium ions for encapsulation of green tea flavonoids

Chondroitin sulphate is a sulphated glycosaminoglycan biopolymer composed over 100 individual sugars. Chondroitin sulphate nanoparticles (NPs) loaded with catechin were prepared by an ionic gelation method using AlCl₃ and optimised for polymer and cross‐linking agent concentration, curing time and stirring speed. Zeta potential, particle size, loading efficiency, and release efficiency over 24 h (RE₂₄ %) were evaluated. The surface morphology of NPs was investigated by scanning electron microscopy and their thermal behaviour by differential scanning calorimetric. Antioxidant effect of NPs was determined by chelating activity of iron ions. The cell viability of mesenchymal stem cells was determined by 3‐[4, 5‐dimethylthiazol‐2‐yl]‐2, 5‐diphenyl tetrazolium bromide assay and the calcification of osteoblasts was studied by Alizarin red staining. The optimised NPs showed particle size of 176 nm, zeta potential of −20.8 mV, loading efficiency of 93.3% and RE₂₄ % of 80.6%. The chatechin loaded chondroitin sulphate NPs showed 70‐fold more antioxidant activity, 3‐fold proliferation effect and higher calcium precipitation in osteoblasts than free catechin.Inspec keywords: nanoparticles, encapsulation, biomedical materials, particle size, nanofabrication, nanomedicine, electrokinetic effects, cellular biophysics, polymer blends, molecular biophysics, molecular configurations, biochemistry, curing, surface morphology, scanning electron microscopy, differential scanning calorimetry, dyes, precipitationOther keywords: in vitro evaluation, cross‐linked chondroitin sulphate nanoparticles, aluminium ions, nanoparticles, green tea flavonoids, sulphated glycosaminoglycan biopolymer, sugars, catechin, ionic gelation method, cross‐linking agent concentration, curing time, size 176 nm, time 24 h, calcium precipitation, 3‐fold proliferation effect, antioxidant activity, chatechin loaded chondroitin sulphate NPs, Alizarin red staining, osteoblasts, calcification, 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5‐diphenyl tetrazolium bromide assay, mesenchymal stem cells, cell viability, chelating activity, differential scanning calorimetry, thermal behaviour, scanning electron microscopy, surface morphology, release efficiency, loading efficiency, particle size, zeta potential, stirring speed     

Development and in vitro evaluation of oxytetracycline‐loaded PMMA nanoparticles for oral delivery against anaplasmosis

Poly‐methyl methacrylate (PMMA) polymer with remarkable properties and merits are being preferred in various biomedical applications due to its biocompatibility, non‐toxicity and cost effectiveness. In this investigation, oxytetracycline‐loaded PMMA nanoparticles were prepared using nano‐precipitation method for the treatment of anaplasmosis. The prepared nanoparticles were characterised using dynamic light scattering (DLS), atomic force microscopy (AFM), differential scanning calorimetry (DSC) and Fourier transform infrared (FTIR) spectroscopy. The mean average diameter of the nanoparticles ranged between 190–240 nm and zeta potential was found to be −19 mV. The drug loading capacity and entrapment efficiency of nanoparticles was found varied between 33.7–62.2% and 40.5–60.0%. The in vitro drug release profile exhibited a biphasic phenomenon indicating controlled drug release. The uptake of coumarin‐6(C‐6)‐loaded PMMA nanoparticles in Plasmodium falciparum (Pf 3D7) culture model was studied. The preferential uptake of C‐6‐loaded nanoparticles by the Plasmodium infected erythrocytes in comparison with the uninfected erythrocytes was observed under fluorescence microscopy. These findings suggest that oxytetracycline‐loaded PMMA nanoparticles were found to be an effective oral delivery vehicle and an alternative pharmaceutical formulation in anaplasmosis treatment, too.Inspec keywords: nanoparticles, nanomedicine, conducting polymers, microorganisms, cellular biophysics, toxicology, drug delivery systems, light scattering, atomic force microscopy, differential scanning calorimetry, Fourier transform infrared spectra, bloodOther keywords: in vitro evaluation, oxytetracycline‐loaded PMMA nanoparticles, anaplasmosis, polymethyl methacrylate polymer, biocompatibility, toxicity, oxytetracycline‐nanoparticles, nanoprecipitation method, dynamic light scattering, atomic force microscopy, AFM, differential scanning calorimetry, DSC, Fourier transform infrared spectroscopy, FTIR spectroscopy, zeta potential, drug loading capacity, entrapment efficiency, in vitro drug release profile, biphasic phenomenon, coumarin‐6(C‐6)‐loaded PMMA nanoparticles, plasmodium falciparum culture model, preferential uptake, plasmodium infected erythrocytes, fluorescence microscopy, oral delivery vehicle, anaplasmosis treatment, size 190 nm to 240 nm     

Factorial design analysis and optimisation of chitosan‐based nanogels as controlled release system for gentamicin

The aim of this study was preparation and optimisation of a controlled‐release delivery system to decrease the dose‐dependent side effects of gentamicin. Hydrogel nanoparticles composed of a polycationic polymer (chitosan) and an inorganic polyanion (sodium tripolyphosphate) were fabricated in the presence of gentamicin. An experimental design was drawn upon to determine the optimum condition of nanoparticle preparation. Various features of the nanoparticles including drug loading parameters, particle size distribution, zeta potential and in vitro drug release profile were evaluated. Ultimately, the antimicrobial activity of the gentamicin‐loaded nanoparticles was analysed by determination of the minimum inhibitory concentration (MIC) and the potency test. As a result, the nanocarriers with an average size of about 250 nm (unloaded) and 493 nm (gentamicin‐loaded) were obtained with unimodal distribution and a notable polydispersity index (≤0.3). The drug loading efficiency was between 28 and 32%. The gradual and sustained releases (∼90%) of gentamicin were achieved in 24 h. The MIC and potency test showed no significant decrease in the antibacterial activity of gentamicin‐loaded nanoparticles. The outcomes demonstrated that the optimised chitosan nanogels prepared in this study can be considered as a suitable carrier for a controlled release system.Inspec keywords: hydrogels, nanoparticles, drug delivery systems, particle size, electrokinetic effects, antibacterial activity, nanomedicineOther keywords: factorial design analysis, chitosan‐based nanogels, gentamicin, controlled‐release delivery system, hydrogel nanoparticles, polycationic polymer, inorganic polyanion, sodium tripolyphosphate, particle size distribution, drug loading parameters, zeta potential, in vitro drug release profile, antimicrobial activity, minimum inhibitory concentration, polydispersity index, drug loading efficiency, antibacterial activity     

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     

Preparation and characterisation of atorvastatin and curcumin‐loaded chitosan nanoformulations for oral delivery in atherosclerosis

Atorvastatin known to be a potential inhibitor of HMG‐CoA reductase involved in the synthesis of cholesterol. It is touted as miracle drug due to its profound effect in decreasing the low‐density lipoproteins in blood. Unfortunately, the high dosage used poses side‐effects relatively in comparison to other statins. On the other hand, curcumin has a diverse therapeutic potential in health and disease. However, the poor aqueous solubility and low bioavailability hinders the therapeutic potential of it when administrated orally. Therefore, it was thought to minimise the frequency of atorvastatin doses to avoid the possibility of drug resistance and also to overcome the limitations of curcumin for desirable therapeutic effects by using nanocarriers in drug delivery. In this investigation, synergistic effect of atorvastatin and curcumin nanocarriers was encapsulated by chitosan polymer. The chitosan nanocarriers prepared by ionic gelation method were characterised for their particle size, zeta potential, and other parameters. The drug‐loaded nanocarriers exhibited good encapsulation efficiency (74.25%) and showed a slow and sustained release of atorvastatin and curcumin 60.36 and 61.44%, respectively, in a span of 48 h. The drug‐loaded nanocarriers found to be haemocompatible and qualified for drug delivery in atherosclerosis.Inspec keywords: nanomedicine, drug delivery systems, diseases, cardiovascular system, enzymes, nanofabricationOther keywords: atorvastatin chitosan nanoformulation, curcumin‐loaded chitosan nanoformulation, oral delivery, atherosclerosis, potential inhibitor, HMG‐CoA reductase, cholesterol synthesis, miracle drug, low‐density lipoproteins, blood, diverse therapeutic potential, poor aqueous solubility, low bioavailability, drug resistance, nanocarriers, ionic gelation method, particle size, zeta potential, encapsulation efficiency     

Fluorescein isothiocyanate‐dyed mesoporous silica nanoparticles for tracking antioxidant delivery

This study investigated the cellular uptake of fluorescein isothiocyanate‐labelled mesoporous silica nanoparticles (FITC‐MSNs), amine‐functionalised FITC‐MSNs (AP‐FITC‐MSNs) and their gallic acid (GA)‐loaded counterparts. Mesoporous silica nanoparticles were labelled with fluorescein isothiocyanate, functionalised by 3‐aminopropyltriethoxysilane (APTES) (AP‐FITC‐MSNs) and then loaded by GA. All nanoparticles were characterised by transmission electron microscopy (TEM), Fourier transform infrared spectroscopy, and X‐ray diffraction. The cytotoxicity of different concentrations of dyed nanoparticles was investigated using (3‐(4,5‐trihydroxybenzoic acid, dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide) assay and flow cytometry. TEM images showed that the average particle sizes of FITC‐MSNs and AP‐FITC‐MSNs were about 100 and 110 nm, respectively. These nanoparticles were internalised by Caco‐2 cells, accumulated and dispersed into the cytoplasm, nucleus, and subcellular organelles. Nanoparticles containing GA clearly decreased the viability of cells. FITC‐MSNs showed no toxicity on Caco‐2 cells at concentrations of ≤50 µg/ml. Functionalisation of FITC‐MSNs using APTES decreased toxicity effects on the cells. It was found that FITC‐MSNs can be applied at low concentrations as a marker in the cells. In addition, AP‐FITC‐MSNs showed better biocompatibility with Caco‐2 cells than FITC‐MSNs, because of their positive surface charges.Inspec keywords: mesoporous materials, porosity, nanoparticles, dyes, silicon compounds, nanocomposites, nanofabrication, nanomedicine, cellular biophysics, molecular biophysics, biochemistry, transmission electron microscopy, Fourier transform infrared spectra, X‐ray diffraction, toxicology, particle size, biomedical materials, surface charging, cancerOther keywords: fluorescein isothiocyanate‐dyed mesoporous silica nanoparticles, antioxidant delivery tracking, cellular uptake, amine‐functionalised FITC‐MSNs, gallic acid‐loaded counterparts, 3‐aminopropyltriethoxysilane, transmission electron microscopy, TEM, Fourier transform infrared spectroscopy, X‐ray diffraction, cytotoxicity, dyed nanoparticles, (3‐(4,5‐trihydroxybenzoic acid‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide) assay, flow cytometry, particle sizes, AP‐FITC‐MSNs, Caco‐2 cells, cytoplasm, subcellular organelles, cell viability, biocompatibility, positive surface charges, 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     

5 Fluorouracil‐loaded biosynthesised gold nanoparticles for the in vitro treatment of human pancreatic cancer cell

In this study, green synthesis of gold nanoparticles (AuNPs) was performed by a sunlight irradiation method using the Borassus flabellifer fruit extract as a reducing agent. 5‐Fluorouracil (5‐FU)‐loaded GG capped AuNPs (5FU‐G‐AuNPs) was prepared. The nanoparticles was further characterised by UV‐visible spectra, particle size analysis, zeta potential, SAED, HRTEM, and XRD. The MTT assay results showed the suitability 5‐FU‐G‐AuNPs. In this study, 5‐FU‐G‐AuNPs exhibited potential cytotoxic and apoptotic effects on (MiaPaCa‐2) cell line.Inspec keywords: gold, biochemistry, X‐ray diffraction, nanofabrication, biomedical materials, transmission electron microscopy, toxicology, electrokinetic effects, particle size, nanoparticles, cancer, visible spectra, cellular biophysics, ultraviolet spectra, nanomedicine, patient treatment, organic compoundsOther keywords: 5FU‐G‐AuNPs, suitability 5‐FU‐G‐AuNPs, human pancreatic cancer cell, green synthesis, sunlight irradiation method, 5‐Fluorouracil‐loaded GG, in vitro treatment, 5 fluorouracil‐loaded biosynthesised gold nanoparticles, borassus flabellifer fruit extract, reducing agent, UV‐visible spectra, particle size analysis, zeta potential, SAED, HRTEM, XRD, MTT assay, apoptotic effects, cytotoxic effects, MiaPaCa‐2 cell line, Au     

Synthesis of biotin‐targeted chitosan/poly (methyl vinyl ether‐alt ‐maleic acid) copolymeric micelles for delivery of doxorubicin

Biotinylated chitosan/poly(methyl vinyl ether‐alt ‐maleic acid) (PMVEMA) copolymer was synthesised by an amide reaction in two steps. Structural characterisation was performed using ¹ HNMR and Fourier transform infra‐red (FTIR) spectra. Critical micelle concentration (CMC) of the copolymer was determined by pyrene as a fluorescent probe. Doxorubicin (DOX) was loaded in the micelles by the direct dissolution method. The effects of different variables including type of copolymer, copolymer concentration, stirring rate and stirring time were studied on the physicochemical properties of the micelles including: particle size, zeta potential, release efficiency and loading efficiency of nanoparticles using an irregular factorial design. The in vitro cytotoxicity of DOX‐loaded biotin‐targeted micelles was studied in HepG2 cells which over express biotin receptors by 3, 5‐[dimethylthiazol‐2‐yl]‐2, 5‐diphenyl tetrazolium bromide assay. The successful synthesis of the biotinylated copolymer of chitosan/PMVEMA was confirmed by FTIR and ¹ HNMR. The optimised micelles showed the CMC of 33 μg/ml, particle size of 247 ± 2 nm, zeta potential of +9.46 mV, polydispersity index of 0.22, drug‐loading efficiency of 71% and release efficiency of 84.5 ± 1.6%. The synthesised copolymer was not cytotoxic. The cytotoxicity of DOX‐loaded in targeted micelles on HepG2 cell line was about 2.2‐fold compared with free drug.Inspec keywords: biomedical materials, cellular biophysics, dissolving, drug delivery systems, drugs, electrokinetic effects, fluorescence, Fourier transform infrared spectra, particle size, polymer blends, spectrochemical analysis, toxicologyOther keywords: ¹ HNMR spectra, biotin‐targeted chitosan‐poly (methyl vinyl ether‐alt‐maleic acid) copolymeric micelles, doxorubicin delivery, amide reaction, structural characterisation, Fourier transform infrared spectra, pyrene, fluorescent probe, direct dissolution method, physicochemical properties, particle size, zeta potential, nanoparticles, irregular factorial design, in vitro cytotoxicity, DOX‐loaded biotin‐targeted micelles, 3, 5‐[dimethylthiazol‐2‐yl]‐2, 5‐diphenyl tetrazolium bromide assay, polydispersity index, drug‐loading efficiency, HepG2 cell line, voltage 9.46 mV     

Preparation and characterisation of ciprofloxacin‐loaded silver nanoparticles for drug delivery

Silver nanoparticles (AgNPs) have shown potential applications in drug delivery. In this study, the AgNPs was prepared from silver nitrate in the presence of alginate as a capping agent. The ciprofloxacin (Cipro) was loaded on the surface of AgNPs to produce Cipro‐AgNPs nanocomposite. The characteristics of the Cipro‐AgNPs nanocomposite were studied by X‐ray diffraction (XRD), UV–Vis, transmission electron microscopy (TEM), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), Fourier‐transform infra‐red analysis (FT‐IR) and zeta potential analyses. The XRD of AgNPs and Cipro‐AgNPs nanocomposite data showed that both have a crystalline structure in nature. The FT‐IR data indicate that the AgNPs have been wrapped by the alginate and loaded with the Cipro drug. The TEM image showed that the Cipro‐AgNPs nanocomposites have an average size of 96 nm with a spherical shape. The SEM image for AgNPs and Cipro‐AgNPs nanocomposites confirmed the needle‐lumpy shape. The zeta potential for Cipro‐AgNPs nanocomposites exhibited a positive charge with a value of 6.5 mV. The TGA for Cipro‐AgNPs nanocomposites showed loss of 79.7% in total mass compared to 57.6% for AgNPs which is due to the Cipro loaded in the AgNPs. The release of Cipro from Cipro‐AgNPs nanocomposites showed slow release properties which reached 98% release within 750 min, and followed the Hixson–Crowell kinetic model. In addition, the toxicity of AgNPs and Cipro‐AgNPs nanocomposites was evaluated using normal (3T3) cell line. The present work suggests that Cipro‐AgNPs are suitable for drug delivery.     

Biogenic synthesis of silver nanoparticles from Cassia fistula (Linn.): In vitro assessment of their antioxidant,antimicrobial and cytotoxic activities

The present study reports on biogenic‐synthesised silver nanoparticles (AgNPs) derived by treating Ag ions with an extract of Cassia fistula leaf, a popular Indian medicinal plant found in natural habitation. The progress of biogenic synthesis was monitored time to time using a ultraviolet–visible spectroscopy. The effect of phytochemicals present in C. fistula including flavonoids, tannins, phenolic compounds and alkaloids on the homogeneous growth of AgNPs was investigated by Fourier‐transform infrared spectroscopy. The dynamic light scattering studies have revealed an average size and surface Zeta potential of the NPs as, −39.5 nm and −21.6 mV, respectively. The potential antibacterial and antifungal activities of the AgNPs were evaluated against Bacillus subtilis, Staphylococcus aureus, Candida kruseii and Trichophyton mentagrophytes. Moreover, their strong antioxidant capability was determined by radical scavenging methods (1,1‐diphenyl‐2‐picryl‐hydrazil assay). Furthermore, the AgNPs displayed an effective cytotoxicity against A‐431 skin cancer cell line by 3‐(4, 5‐dimethylthiazol‐2‐yl)‐2, 5‐diphenyltetrazolium bromide (MTT) assay, with the inhibitory concentration (IC₅₀) predicted as, 92.2 ± 1.2 μg/ml. The biogenically derived AgNPs could find immense scope as antimicrobial, antioxidant and anticancer agents apart from their potential use in chemical sensors and translational medicine.Inspec keywords: antibacterial activity, biomedical materials, cancer, cellular biophysics, electrokinetic effects, Fourier transform infrared spectra, light scattering, microorganisms, nanomedicine, nanoparticles, silver, skin, spectrochemical analysis, toxicology, ultraviolet spectra, visible spectraOther keywords: Ag, voltage ‐21.6 mV, size ‐39.5 nm, A‐431 skin cancer cell line, cytotoxicity, 1,1‐diphenyl‐2‐picryl‐hydrazil assay, radical scavenging methods, Trichophyton mentagrophytes, Candida kruseii, Staphylococcus aureus, Bacillus subtilis, surface zeta potential, dynamic light scattering studies, Fourier‐transform infrared spectroscopy, alkaloids, phenolic compounds, tannins, flavonoids, phytochemical effect, ultraviolet‐visible spectroscopy, Cassia fistula leaf extract, biogenic‐synthesised silver nanoparticles, cytotoxic activities, antimicrobial activities, antioxidant activities     

Enhanced stability of L‐asparaginase by its bioconjugation to poly(styrene‐co‐maleic acid) and Ecoflex nanoparticles

Acute lymphoblastic leukemia (ALL) is the white blood cell cancer in children. L‐asparaginase (L‐ASNase) is one of the first drugs used in ALL treatment. Anti‐tumor activity of L‐ASNase is not specific and indicates limited stability in different biological environments, in addition to its quick clearance from blood. The purpose of the present study was to achieve a new L‐ASNase polymer bioconjugate to improve pharmacokinetic, increase half‐life and stability of the enzyme. The conjugations were achieved by the cross‐linking agent of 1‐ethyl‐3‐(3‐ dimethylaminopropyl) carbodiimide (EDC) which activates the carboxylic acid groups of polymeric nanoparticles to create amide bond. EDC conjugated the L‐ASNase to two biodegradable polymers including; Ecoflex^® and poly (styrene‐co‐maleic acid) (PSMA) nanoparticles. To achieve optimal L‐ASNase nanoparticles the amounts of each polymer and the crosslinker were optimized and the nanoparticles were characterized according to their particle size, zeta potential and percent of conjugation of the enzyme. The results showed that conjugated enzyme had more stability against pH changes and proteolysis. It had lower Km value (indicating more affinity to the substrate) and greater half‐life in plasma and phosphate buffered saline, in comparison to native enzyme. Generally, the conjugated enzyme to PSMA nanoparticles showed greater results than Ecoflex^® nanoparticles.Inspec keywords: enzymes, polymer blends, nanomedicine, biomedical materials, blood, nanoparticles, cancer, molecular biophysics, molecular configurations, biochemistry, conducting polymers, electrokinetic effects, particle size, bonds (chemical), biodegradable materials, pHOther keywords: enhanced stability, L‐asparaginase, bioconjugation, poly(styrene‐co‐maleic acid), Ecoflex nanoparticles, acute lymphoblastic leukaemia, white blood cell cancer, children, drugs, ALL treatment, antitumour activity, biological environments, L‐ASNase polymer bioconjugate, pharmacokinetic, enzyme, crosslinking agent, amide bond, 1‐ethyl‐3‐(3‐dimethylaminopropyl) carbodiimide, carboxylic acid groups, polymeric nanoparticles, EDC conjugation, biodegradable polymers, PSMA nanoparticles, optimal L‐ASNase nanoparticles, particle size, zeta potential, pH changes, proteolysis, native enzyme, conjugated enzyme     

Biosynthesis of zinc oxide nanoparticles using anjbar (root of Persicaria bistorta) extract and their cytotoxic effects on human breast cancer cell line (MCF‐7)

Biosynthesis of nanoparticles (NPs) using biomass is now one of the best methods for synthesising NPs due to their nontoxic and biocompatibility. Plants are the best choice among all biomass to synthesise large‐scale NPs. The objectives of this study were to synthesise zinc oxide nanoparticles (ZnO‐NPs) using Anjbar (root of Persicaria bistorta) [An/ZnO‐NPs] and investigate the cytotoxic and anti‐oxidant effects. For this purpose, the An/ZnO‐NPs were synthesised by using Bistort extract and characterised using UV–Visible spectroscopy, transmission electron microscope, field emission scanning electron microscope, x‐ray diffraction and Fourier‐transform infrared spectroscopy. The cytotoxic effects of the An/ZnO‐NPs on MCF‐7 cells were followed by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assays at 24, 48, and 72 h. Nuclear morphology changed and apoptosis in cells was investigated using acridine orange/propodium iodide (AO/PI) staining and flow cytometry analysis. The pure biosynthesised ZnO‐NPs were spherical in shape and particles sizes ranged from 1 to 50 nm. Treated MCF‐7 cells with different concentrations of ZnO‐NPs inhibited cell viability in a time‐ and dose‐dependent manner with IC50 about 32 μg/ml after 48 h of incubation. In flow cytometry analysis the sub‐G1 population, which indicated apoptotic cells, increased from 12.6% at 0 μg/ml (control) to 92.8% at 60 μg/ml, 48 h after exposure. AO/PI staining showed that the treated cells displayed morphologic evidence of apoptosis, compared to untreated groups. Inspec keywords: cancer, cellular biophysics, toxicology, particle size, nanofabrication, X‐ray diffraction, nanomedicine, nanoparticles, ultraviolet spectra, scanning electron microscopy, visible spectra, transmission electron microscopy, patient treatment, field emission electron microscopy, Fourier transform infrared spectra, drug delivery systemsOther keywords: anjbar, cytotoxic effects, human breast cancer cell line, biomass, transmission electron microscope, field emission scanning electron microscope, Fourier‐transform infrared spectroscopy, flow cytometry analysis, ZnO‐NPs inhibited cell viability, antioxidant effects, MCF‐7 cells, biosynthesised ZnO‐NP, biosynthesised ZnO‐NP, acridine orange‐propodium iodide staining, An‐ZnO‐NP, Persicaria bistorta, zinc oxide nanoparticle biosynthesis, 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide     

Honokiol–camptothecin loaded graphene oxide nanoparticle towards combinatorial anti‐cancer drug delivery

Honokiol (HK) is a natural product isolated from the bark, cones, seeds and leaves of plants belonging to the genus Magnolia. It possesses anti‐cancer activity which can efficiently impede the growth and bring about apoptosis of a diversity of cancer cells. The major concerns of using HK are its poor solubility and lack of targeted drug delivery. In this study, a combinatorial drug is prepared by combining HK and camptothecin (CPT). Both CPT and HK belong to the Magnolian genus and induce apoptosis by cell cycle arrest at the S‐phase and G1 phase, respectively. The combinatorial drug thus synthesised was loaded onto a chitosan functionalised graphene oxide nanoparticles, predecorated with folic acid for site‐specific drug delivery. The CPT drug‐loaded nanocarrier was characterised by X‐ray diffractometer, scanning electron microscope, transmission electron microscope, UV–vis spectroscopy and fluorescence spectroscopy, atomic force microscopy. The antioxidant properties, haemolytic activity and anti‐inflammatory activities were analysed. The cellular toxicity was analysed by 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐Diphenyltetrazolium Bromide (MTT assay) and Sulforhodamine B (SRB) assay against breast cancer (MCF‐7) cell lines.Inspec keywords: nanofabrication, cancer, nanoparticles, atomic force microscopy, graphene, scanning electron microscopy, cellular biophysics, toxicology, transmission electron microscopy, drug delivery systems, nanomedicine, tumours, solubilityOther keywords: targeted drug delivery, combinatorial drug, Magnolian genus, apoptosis, cell cycle, chitosan functionalised graphene oxide nanoparticles, site‐specific drug delivery, CPT drug‐loaded nanocarrier, transmission electron microscope, fluorescence spectroscopy, haemolytic activity, antiinflammatory activities, breast cancer cell lines, honokiol–camptothecin loaded graphene oxide nanoparticle, combinatorial anti‐cancer drug delivery, natural product, genus Magnolia, anticancer activity, cancer cells     

Evaluation of betamethasone sodium phosphate loaded chitosan nanoparticles for anti‐rheumatoid activity

Nanocarriers, in various forms, have the possibility of providing endless opportunities in the area of drug delivery. The purpose of this study was formulation and evaluation of betamethasone sodium phosphate (BSP) loaded chitosan nanoparticles (CNPs) using cross‐linked chitosan malic acid derivative for better therapeutic effect. The prepared BSP loaded CNPs formulations were characterised for photon correlation spectroscopy, zeta potential, transmission electron microscopy, in‐vitro release kinetics and in‐vivo toxicity studies. Mean particle diameter of BSP loaded CNPs was about 130 nm with spherical morphology. The in‐vitro drug release study of BSP loaded CNPs showed sustained drug release for 48 h and drug release was found to follow zero order. The biochemical, haematology and histopathology reports of in‐vivo toxicity studies revealed that BSP loaded CNPs do not exhibit any toxic effect on vital organs and could be safe. The developed BSP loaded CNPs are found to be safer, and used for the treatments of highly prevalent and chronic disease like rheumatoid arthritis.Inspec keywords: nanoparticles, drug delivery systems, electrokinetic effects, toxicology, photon correlation spectroscopy, transmission electron microscopy, diseases, organic compounds, nanomedicineOther keywords: betamethasone sodium phosphate, chitosan nanoparticles, antirheumatoid activity, nanocarriers, drug delivery, cross‐linked chitosan malic acid derivative, photon correlation spectroscopy, zeta potential, transmission electron microscopy, in‐vitro release kinetics, in‐vivo toxicity, spherical morphology, rheumatoid arthritis     

Method development for optimised green synthesis of gold nanoparticles from Millettia pinnata and their activity in non‐small cell lung cancer cell lines

Green synthesis of gold nanoparticles (GNPs) has received substantial attention, because nanoparticles are produced in an eco‐friendly way using biomolecules present in plant extracts in a single step reaction. This research article highlights GNPs obtained using shade‐dried leaf extracts of Millettia pinnata (L.) with aqueous auric chloride (HAuCl₄) at ambient temperature. In the present study, GNPs with average particle size 37 nm in size were fabricated. Furthermore, the synthesis method to obtain stable and monodispersed GNPs was advanced by optimising enzyme concentration 100 μg/ml, pH 5.4, substrate concentration 0.45 mM and 12 h time of reaction. The confirmation of GNPs formation and characterisation was followed by UV‐vis‐absorption spectroscopy, dynamic light scattering (DLS), and zeta potential (ZP) for the analysis of shape, size, and stability, respectively. TEM images and powder XRD revealed the GNPs synthesis of spherical‐shaped nanoparticles in the face‐centred cubic arrangement. Cytotoxicity of GNPs was studied against A549 lung cancer cells with IC₅₀ 14.76 μg/ml and found lower as compared to doxorubicin IC₅₀ 11.23 μg/ml but significant enough to be used as a vehicle GNPs produced using green source can be used as significant therapeutic agents and drug delivery carriers.Inspec keywords: nanomedicine, molecular biophysics, cancer, electrokinetic effects, pH, transmission electron microscopy, toxicology, gold, cellular biophysics, X‐ray diffraction, lung, biomedical materials, nanofabrication, nanoparticles, particle size, enzymes, visible spectra, ultraviolet spectra, light scattering, biochemistryOther keywords: method development, optimised green synthesis, gold nanoparticles, millettia pinnata, nonsmall cell lung cancer cell lines, plant extracts, single step reaction, shade‐dried leaf extracts, aqueous auric chloride, synthesis method, stable GNPs, monodispersed GNPs, spherical‐shaped nanoparticles, A549 lung cancer cells, green source, particle size, enzyme concentration, substrate concentration, biomolecules, reaction time, UV‐visible‐absorption spectroscopy, dynamic light scattering, zeta potential, TEM images, powder XRD, face‐centred cubic arrangement, cytotoxicity, pH, therapeutic agents, drug delivery carriers, time 12.0 hour, Au     

RES‐loaded pegylated CS NPs: for efficient ocular delivery

The objective of this study is to develop resveratrol (RES) loaded polyethylene glycols (PEGs) modified chitosan (CS) nanoparticles (NPs) by ionic gelation method for the treatment of glaucoma. While increasing the concentration of PEG, the particle size and polydispersity index of the formulations increased. Entrapment efficiency and RES loading (RL) of NPs decreased while increasing PEG concentration. The in vitro release of NPs showed an initial burst release of RES (45%) followed by controlled release. Osmolality of formulations revealed that the prepared NPs were iso‐osmolar with the tear. Ocular tolerance of the NPs was evaluated using hen''s egg test on the chorioallantoic membrane and it showed that the NPs were non‐irritant. RES‐loaded PEG‐modified CS NPs shows an improved corneal permeation compared with RES dispersion. Fluorescein isothiocyanate loaded CS NPs accumulated on the surface of the cornea but the PEG‐modified CS NPs crossed the cornea and reached retinal choroid. RES‐loaded PEG‐modified CS NPs reduced the intra‐ocular pressure (IOP) by 4.3 ± 0.5 mmHg up to 8 h in normotensive rabbits. These results indicate that the developed NPs have efficient delivery of RES to the ocular tissues and reduce the IOP for the treatment of glaucoma.Inspec keywords: conducting polymers, nanoparticles, nanomedicine, drug delivery systems, particle size, nanofabrication, organic compounds, biomembranes, cellular biophysics, eye, vision defects, biological tissuesOther keywords: RES‐loaded pegylated CS NP, efficient ocular delivery, resveratrol loaded polyethylene glycol modified chitosan nanoparticles, ionic gelation method, glaucoma treatment, particle size, polydispersity index, entrapment efficiency, RES loading, PEG concentration, in vitro release, osmolality formulations, ocular tolerance, hen egg testing, chorioallantoic membrane, improved corneal permeation, RES dispersion, fluorescein isothiocyanate loaded CS NP, cornea surface, reached retinal choroid, intraocular pressure, normotensive rabbits, RES delivery, ocular tissues