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     

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     

Atorvastatin lipid nanocapsules and gold nanoparticles embedded in injectable thermo‐gelling hydrogel scaffold containing adipose tissue extracellular matrix for myocardial tissue regeneration

This study aimed to prepare, optimise, and characterise the novel hybrid hydrogel scaffold containing atorvastatin lipid nanocapsules (LNCs) and gold nanoparticles (NPs) to improve cardiomyoblasts proliferation and regeneration of myocardium. A thermo‐responsive aminated guaran (AGG) hydrogel was prepared to encompass extracellular matrix (ECM) fetched from human adipose tissue. Emulsion phase‐inversion technique was used to obtain LNCs. Biocompatibility, tensile strength, conductivity, and proliferation of human myocardial cells of the optimised formulation were studied. The LNCs have a spherical shape, and the optimised formulation showed a mean particle size of 18.79 nm, the zeta potential of − 11.4 mV, drug loading of 99.99%, and release efficiency percent over 72 h was 18.73%. The injectable thermo‐sensitive hydrogel prepared using 1 w/v% of AGG, 35 w/w% of ECM, ∼0.5 mg/ml of gold NPs and atorvastatin loaded LNCs showed the best physical characteristics. The hybrid scaffold loaded with atorvastatin and gold NPs improved the proliferation of cardiomyoblasts more than sevenfold with enhanced cell attachment to the scaffold. The tensile strength and the conductivity of the scaffold were 300 kPa and 0.14 S/m, respectively. Injectable hybrid adipose tissue prepared by ECM and AGG hydrogel loaded with atorvastatin and gold NPs showed promising physical characteristics for myocardial tissue engineering.Inspec keywords: biological tissues, nanoparticles, tensile strength, electrokinetic effects, particle size, nanomedicine, emulsions, biomedical materials, cellular biophysics, nanofabrication, drugs, drug delivery systems, molecular biophysics, tissue engineering, hydrogels, goldOther keywords: Au, cardiomyoblast, hybrid hydrogel scaffold, myocardial tissue engineering, AGG hydrogel, injectable hybrid adipose tissue, atorvastatin loaded LNCs, gold NPs, thermo‐sensitive hydrogel, drug loading, human myocardial cells, tensile strength, emulsion phase‐inversion technique, human adipose tissue, ECM, thermo‐responsive aminated guaran hydrogel, cardiomyoblasts proliferation, atorvastatin lipid nanocapsules, myocardial tissue regeneration, adipose tissue extracellular matrix, thermo‐gelling hydrogel scaffold, gold nanoparticles     

Hesperetin-Loaded Solid Lipid Nanoparticles and Nanostructure Lipid Carriers for Food Fortification: Preparation, Characterization, and Modeling

Solid lipid nanoparticles and nanostructure lipid carriers were used to entrap hesperetin and broaden confined knowledge of application of nanocarriers as the functional ingredients in food sectors. The produced nanocarriers using a high mechanical shear method were subjected to size and zeta potential analysis. The developed nanosize carriers had the encapsulation efficiency ranging from 39.90 to 63.08 %. Differential scanning calorimetry, X-ray diffraction, and Fourier transform infrared spectroscopy were also employed to study thermal behavior, crystalline state, and chemical structure. The release behavior of hesperetin in simulated gastrointestinal conditions was investigated and kinetically modeled. The modeling results indicated that the release phenomenon is mostly governed by combination of Fickian and dissolution mechanisms. Stability of the nanocarriers, as analyzed for up to 30 days, at 6 and 25 °C in aqueous suspension, showed no detectable hesperetin leakage. Cryoprotectant effect of different compounds (i.e., glucose, sorbitol, glycerin, lactose, and sucrose) was also examined. Finally, the potential capability of nanocarriers for food fortification was studied using milk as a model food. The fortified milk samples were subjected to sensory analysis and results betokened that the developed nanocarriers did not show any significant difference with blank milk sample and could well mask the bitter taste, after taste, and obviate poor solubility of hesperetin.     

Dissolution enhancement of gliclazide using in situ micronization by solvent change method

Gliclazide (GL) is a second-generation sulphonylurea, widely used for the treatment of non-insulin dependent diabetes mellitus. The low water-solubility of GL leads to a low dissolution rate and variable bioavailability. The aim of this study was to enhance the dissolution rate of GL by the preparation of micron-sized particles using a solvent change method. The in situ micronization process was carried out using solvent change method in the presence of HPMC or Brij 35 (0.05 or 0.1 g) as stabilizing agents. GL (0.5 or 1 g) was dissolved in acetone and the stabilizing agent in water (as non-solvent). The non-solvent was poured rapidly into the drug solution under stirring at 26,000 rpm by an ultra-homogenizer, and the resultant was freeze-dried. The crystalline shape of GL changed from rod-shape to diamond- or cube-shape. The FTIR and DSC results showed no interaction between the drug and the stabilizers. Presence of sharp peaks in the XRD diffractograms of microcrystals with 10 times smaller height than untreated crystals indicates that a crystalline habit modification has occurred in the microcrystals without any polymorphic changes. The particle size was reduced about 50 times and the dissolution efficiency of GL at 15 min (DE₁₅%) was increased about 4 times.