Acrylic acid–methyl methacrylate copolymer for oral prolonged drug release

Acrylic acid (AA)–methyl methacrylate (MMA) based copolymers, in different molar ratios (3:7, 4:6, 5:5, 6:4, and 7:3) were synthesized using tetrahydrofuran as solvent and AIBN as free radical initiator. Increase in acrylic acid concentration promoted pH-dependent swelling of copolymer and copolymer AA:MMA (3:7) was selected due to minimum swelling. ATR/FTIR and ¹H NMR spectra of the copolymer showed absence of vinyl bond/protons present in the monomers suggesting successful polymerization. The copolymer was hemocompatible. Flurbiprofen sodium microspheres made with the copolymer, by oil/oil solvent evaporation, were spherical, anionic (zeta potential −59.0 mV) and contained 4.53% drug. ATR spectrum of microspheres showed peaks for aromatic C=C stretching and substituted benzene ring, indicating entrapment of flurbiprofen. XRD analysis revealed crystalline structure of flurbiprofen while copolymer and microspheres were amorphous. DSC thermograms showed a sharp melting endotherm of flurbiprofen sodium at 129.26°C against broad endotherms of copolymer and microspheres having peaks at 82.24 and 86.59°C, respectively. The thermogram of microspheres did not show the melting peak of flurbiprofen. The microspheres exhibited no drug release at pH <6.8 and released 83.4 and 99% drug at pH 6.8 and 7.4 in 3 h. The microspheres did not adhere on gastric mucosa at pH 1.2 but showed mucoadhesion time of 28 min on intestinal mucosa at pH 6.8. Thus, the microspheres on oral administration, would release the drug in distal ileum, suggesting the potential of the hemocompatible copolymer for enteric coating for prolonged drug release.     

Cobalt hexacyanoferrate–poly(methyl methacrylate) composite: Synthesis and characterization

The preparation of cobalt hexacyanoferrate nanoparticles–poly(methyl methacrylate) (CoHCF–PMMA) composites are described together with their characterization and thermochromic properties. CoHCF nanoparticles – investigated by dynamic light scattering – were prepared by optimizing solvent composition and temperature to obtain nanoparticles with a reduced degree of aggregation. The nanoparticles were embedded in a PMMA matrix to obtain a transparent coloured composite which was studied by transmission electron microscopy. The nanoparticle chromic features, enhanced by their reduced sizes, were investigated by UV–vis and FT-IR spectroscopy.     

In vitro evaluation of compression-coated glycyl-l-histidyl-l-lysine–Cu(II) (GHK–Cu2+)-loaded microparticles for colonic drug delivery

Glycyl-l-histidyl-l-lysine–Cu(II) (GHK–Cu²⁺)-loaded Zn-pectinate microparticles in the form of hydroxypropyl cellulose (HPC) compression-coated tablets were prepared and their in vitro behavior tested. GHK–Cu²⁺ delivery to colon can be useful for the inhibition of matrix metalloproteinase, with the increasing secretion of tissue inhibitors of metalloproteinases (TIMPS),which are the major factors contributing in mucosal ulceration and inflammation in inflammatory bowel disease. The concentration of peptide was determined spectrophotometrically. The results obtained implied that surfactant ratio had a significant effect on percent production yield (1.25 to 1.75 w/w; 72.22% to 80.84%), but cross-linking agent concentration had not. The entrapment efficiency (EE) was found to be in the range of 58.25–78.37%. The drug-loading factor significantly increased the EE; however, enhancement of cross-linking agent concentration decreased it. The release of GHK–Cu²⁺ from Zn-pectinate microparticles (F1–F8) in simulated intestinal fluid was strongly affected by cross-linking agent concentration and drug amount (50?mg for F1–F6; 250?mg for F7–F8), but not particularly affected by surfactant amount. Release profiles represented that the microparticles released 50–80% their drug load within 4?h. Therefore, the optimum microparticle formulation (F8) coated with a relatively hydrophobic polymer HPC to get a suitable colonic delivery system. The optimum colonic delivery tablets prepared with 700?mg HPC-SL provided the expected delayed release with a lag time of 6?h. The effects of polymer viscosity and coat weight on GHK–Cu²⁺ release were found to be crucial for the optimum delay of lag time. The invention was found to be promising for colonic delivery.     

PEGylated nanostructured lipid carriers (PEG–NLC) as a novel drug delivery system for biochanin A

With the aim to develop a lipid nanoparticle for biochanin A (BCA) by emulsion-evaporation and low temperature-solidification technique. The results revealed that BCA–PEG–NLC not only have small mean particle (148.5?±?2.88?nm) with narrow polydispersity index (PI) (0.153?±?0.01), encapsulation capacity (99.62?±?0.06%), payload (9.06?±?0.01%), zeta potential (?19.83?±?1.19?mV), but also slower release rate compared with BCA suspension over 48?h by the dialysis method (n=3). The crystallinity of lipid matrix within BCA–PEG–NLC was evaluated by differential scanning calorimetry (DSC) which verified the BCA successfully into the nanoparticles. Particularly, in pharmacokinetic, the BCA–PEG–NLC of C_max values and AUC (area under curve) was higher than BCA suspension (approximately 15.8 and 2.9 times, respectively), meanwhile, the mean residence time (MRT) was significantly longer. Furthermore, in vitro cytotoxicity BCA–PEG–NLC showed higher cytotoxicity against MCF-7 cell line compared with BCA suspension. This study suggested that PEG–NLC is a novel anti-cancer nanoparticle, which could provide attractive treatment for a wide variety of tumors and improved the oral bioavailability of poorly water-soluble drug.     

Development of an image-based numerical model for predicting the microstructure–property relationship in alumina trihydrate (ATH) filled poly(methyl methacrylate) (PMMA)

Particulate composites are found in a wide range of applications. Their heterogeneous microstructure affects their bulk behavior and structural performance, however tools for predicting this important structure-property relationship are still lacking. In this study, a numerical method that can provide predictions of the mechanical response of a particulate polymeric matrix composite as a function of volume fraction and particle mean diameter is presented. The work is derived for an alumina trihydrate filled poly(methyl methacrylate) but the methodology is generic and can be used for any particulate composite. Representative Volume elements are determined through images obtained from scanning electron microscopy. The model takes into account the possibility of failure through interface debonding as well as cracks through the matrix. The model predictions for the modulus and fracture strength of the composites are validated through independent experiments on the composite. The numerical results are also used to qualitatively explain the trends measured regarding the fracture toughness of the composites. Compared to other literature on particulate composites, our study is the first to report accurate stress–strain distributions as well as fracture predictions whilst all the necessary model parameters defining the failure criteria are all derived through independent experiments. This paves the way for a relatively simple methodology for determining structure-property relationships in composites design, enabling smarter material utilization and optimal mechanical properties.     

High drug loading polymer micelle@ZIF-8 hybrid core–shell nanoparticles through donor–receptor coordination interaction for pH/H2O2-responsive drug release

Smart drug delivery nanocarriers with high drug loading capacity are of great importance in the treatment of diseases, and can improve therapeutic effectiveness as well as alleviate side effects in patients. In this work, a pH and H₂O₂-responsive drug delivery platform with high doxorubicin (DOX) loading capacity has been established through coordination interaction between DOX and phenylboronic acid containing block polymer. A composited drug nanocarrier is further fabricated by growing a zeolitic imidazolate framework 8 (ZIF-8) on the surface of drug-loaded polymer micelles. The study verifies that ZIF-8 shell can act as intelligent “switch” to prevent DOX leaking from core–shell nanoparticles upon H₂O₂ stimulus. However, a burst drug release is detected upon pH and H₂O₂ stimuli due to the further disassociation of ZIF-8 in acid solution. Moreover, the in vitro anti-cancer experiments demonstrate that the DOX-loaded core–shell nanoparticles provide effective treatment towards cancer cells but have negligible effect on normal cells, which results from the high concentration of H₂O₂ and low pH in the microenvironment of tumor cells.     

Polybutylacrylate/poly(methyl methacrylate) Core-Shell Elastic Particles as Epoxy Resin Toughener:Part Ⅰ Design and Preparation

Polybutylacrylate (PBA)/poly(methyl methacrylate) (PM MA) core-shell elastic particles (CSEP), whose rubbery core diameterranged from 0.08 μm to 1.38 μm, were synthesized by using conventional emulsion polymerization, multi-step emulsion polymerization, and soapless polymerization. Allyl methacylate (ALMA) and ethylene glycol dimethacrylate (EGDMA) were selected as crosslinking reagents for core polymerization. Methacrylic acid (MAA) was used as functional co-monomer with methyl methacrylate as shell component. The content of vinyl groups in PBA rubbery core increased with the amount of crosslinking reagents. The core-shell ratio affected great on the morphology of the complex particles. Furthermore, the amounts of carboxyl on the surface of core-shell particles, copolymerized with acrylic acid, were determined by potentiometric titration. Results showed that methylacrylic acid was distributed mostly on the surface of particles.     

Polybutylacrylate/poly(methyl methacrylate) Core-Shell Elastic Particles as Epoxy Resin Toughener: Part I Design and Preparation

Polybutylacrylate (PBA)/poly(methyl methacrylate) (PMMA) core-shell elastic particles (CSEP), whose rubbery core diameter ranged from 0.08 μm to 1.38μm, were synthesized by using conventional emulsion polymerization, multi-step emulsion polymerization, and soapless polymerization. Allyl methacylate (ALMA) and ethylene glycol dimethacrylate (EGDMA) were selected as crosslinking reagents for core polymerization. Methacrylic acid (MAA) was used as functional co-monomer with methyl methacrylate as shell component. The content of vinyl groups in PBA rubbery core increased with the amount of crosslinking reagents. The core-shell ratio affected great on the morphology of the complex particles. Furthermore, the amounts of carboxyl on the surface of core-shell particles, copolymerized with acrylic acid, were determined by potentiometric titration. Results showed that methylacrylic acid was distributed mostly on the surface of particles.     

Polybutylacrylate/poly (methyl methacrylate) Core-Shell Elastic Particles as Epoxy Resin Toughener: Part Ⅱ Toughness on DGEBA/DDM system

Mechanlcal properties of epoxy resin were investigated by adding core-shell elastic particles (CSEP). The results indicated that optimized core-shell ratio was 60/40 and the loading volume of CSEP was 10 phr (per hundred parts of epoxy resin by weight). The impact strength of modified systems increased apparently with the decrease of core sizes. However, the shearing strength changed gently with the particle sizes. CSEP with lightly crosslinked rubbery core showed more effectiveness on toughness than others. With solution blending, CSEP could be dispersed in epoxy matrix well, and the morphologies of dispersed rubber domains were controlled perfectly by CSEP whose structure was predesigned. A cavitation-shearing band toughness mechanism was observed from the SEM micrographs of fracture surface. It also was found that the deforming temperature (DT) of modified epoxy did not decline apparently.     

Development of new ionic gelation strategy: Towards the preparation of new monodisperse and stable hyaluronic acid/β-cyclodextrin-grafted chitosan nanoparticles as drug delivery carriers for doxorubicin

In the present study, β-cyclodextrin-grafted chitosan nanoparticles (β-CD-g-CS NPs) were prepared using a new ionic gelation strategy involving a synergistic effect of NaCl (150 mmol/L), 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES, 10 mmol/L), and water bath sonication. This new strategy afforded smaller and more monodisperse β-CD-g-CS NPs vs. the classical ionic gelation method. New HA/β-CD-g-CS NPs were also prepared using the above-mentioned strategy by adding hyaluronic acid (HA) to the β-CD-g-CS copolymer at different weight ratios until the ZP values conversion. The best result was obtained with the weight ratio of w(HA):w(β-CD-g-CS) = 2:1 and furnished new spherical and smooth HA/β-CD-g-CS NPs. Furthermore, the stability of β- CD-g-CS NPs and HA/β-CD-g-CS NPs at 4°C in physiological medium (pH 7.4) was compared for 3 weeks period and showed that HA/β-CD-g-CS NPs were more stable all maintaining their monodispersity and high negative ZP values compared to β-CD-g-CS NPs. Finally, preliminary study of HA/β-CD-g-CS NPs as carrier for the controlled release of the anticancer drug doxorubicin was investigated. These new HA/β-CD-g-CS NPs can potentially be used as drug delivery and targeting systems for cancer treatment.     

AlGaAs/GaAs multiquantum-well heterostructures for long-wavelength (8–10 μm) IR photodetectors

We have studied AlGaAs/GaAs multiquantum-well heterostructures grown by molecular beam epitaxy in an STE-3532 setup (SemiTEq, St. Petersburg), which are intended for long-wavelength IR photodetectors operating on inter-subband transitions. Quantum wells (QWs) in the obtained heterostructures are highly homogeneous and possess sharp heteroboundaries, which is confirmed by the photoluminescence spectra and dark current-voltage characteristics of photodetectors based on these heterostructures. The photodetectors exhibit sensitivity in the atmospheric transparency window (8?C10 mm) and possess parameters that make possible their use in large-format photodetector arrays for a new generation of long-wavelength IR camera systems.     

Structural,thermal and optical properties of $${\hbox {Cu}}^{2+}$$ doped methacrylic acid–ethyl acrylate (MAA:EA) copolymer films

Pure and \({\hbox {Cu}}^{2+}\) doped methacrylic acid–ethyl acrylate (MAA:EA) copolymer films were prepared using the solution cast technique. The amorphous feature of the copolymer was depicted using X-ray diffraction scans and degree of crystallinity was found to vary with increasing doping content. UV–Vis absorption spectra in the wavelength region 200–900 nm were used to evaluate the optical properties like direct band gap, indirect band gap and absorption edge. The optical band gap decreased with the increase of mol% of \(\hbox {Cu}^{2+}\) ions. Fourier transform infrared spectral studies on pure MAA:EA and \(\hbox {Cu}^{2+}\) ions-doped films revealed the vibrational changes that occurred due to the effect of dopant salt in the copolymer. Thermal properties of these films were investigated by employing differential scanning calorimetry and thermogravimetric analysis. The variation in film morphology was examined by scanning electron microscopy. Electron paramagnetic resonance (EPR) spectra of all the doped samples exhibited signals due to \(\hbox {Cu}^{2+}\) ions with the effective g-values \(g_{\Vert } = 2.177\) and \(g_{\bot }= 2.058\). The observed variation in the EPR signal intensity is due to the isolated and aggregated copper ions. The photoluminescence spectra of \(\hbox {Cu}^{2+}\) ions-doped MAA:EA copolymer exhibited four emission peaks at 480 (blue), 579 (yellow), 604 (red) and 671 nm (red).     

A meshfree method: meshfree weak–strong (MWS) form method,for 2-D solids

A novel meshfree weak–strong (MWS) form method is proposed based on a combined formulation of both the strong-form and the local weak-form. In the MWS method, the problem domain and its boundary is represented by a set of distributed points or nodes. The strong form or the collocation method is used for all nodes whose local quadrature domains do not intersect with natural (Neumann) boundaries. Therefore, no numerical integration is required for these nodes. The local weak-form, which needs the local numerical integration, is only used for nodes on or near the natural boundaries. The locally supported radial point interpolation method and the moving least squares approximation are used to construct the meshfree shape functions. The final system matrix will be sparse and banded for computational efficiency. Numerical examples of two-dimensional solids are presented to demonstrate the efficiency, stability, accuracy and convergence of the proposed meshfree method.     

Surface functionalization of BiFeO<Subscript>3</Subscript>: A pathway for the enhancement of dielectric and electrical properties of poly(methyl methacrylate)–BiFeO<Subscript>3</Subscript> composite films

A novel two-phase composite film is prepared by the solvent casting method employing poly(methyl methacrylate) (PMMA) as polymer matrix and bismuth ferrite (BFO) as ceramic filler. The surfaces of BFO are functionalized by proper hydroxylating agents to activate their chemical nature. The structural analysis of the composite films confirms that the composites made up of functionalized BFO (BFO-OH) have a distorted rhombohedral structure. The morphological analysis shows that BFO-OH particles are equally distributed over the polymer matrix. The -OH functionality of BFO-OH is confirmed by FTIR. The dielectric and electrical studies at a frequency range from 100 Hz to 1 MHz reveal that PMMA-(BFO-OH) composites have enhanced dielectric constant as well as electrical conductivities, much higher than that of unmodified composites. According to the ferroelectric measurement result, the hydroxylated composite film shows a superior ferroelectric behavior than that of the unmodified one, with a remanent polarization (2P_r) of 2.764 μC/cm².     

Corrosion behaviour of single (Ti) and duplex (Ti–TiO2) coating on 304L stainless steel in nitric acid medium

Sputter deposited single titanium (Ti) layer, and duplex Ti–TiO₂ coating on austenitic type 304L stainless steel (SS) was prepared, and the corrosion performance was evaluated in nitric acid medium using surface morphological and electrochemical techniques. Morphological analysis using atomic force microscope of the duplex Ti–TiO₂ coated surface showed minimization of structural heterogeneities as compared to single Ti layer coating. The electrochemical corrosion results revealed that, titanium coated 304L SS showed moderate to marginal improvement in corrosion resistance in 1 M, and 8 M nitric acid, respectively. Duplex Ti–TiO₂ coated 304L SS specimens showed improved corrosion resistance as compared to Ti coating from dilute (1 M) to concentrated medium (8 M). The percentage of protection efficiency for base material increases significantly for duplex Ti–TiO₂ coating as compared to single Ti layer coating. The oxidizing ability of nitric acid on both the coatings as well as factors responsible for improvement in protection efficiency are discussed and highlighted in this paper.     

The system Yb–Ru–O: High temperature studies on the oxides Yb2Ru2O7(s) and Yb3RuO7(s)

The standard molar Gibbs free energy of formation of Yb₂Ru₂O₇(s) and Yb₃RuO₇(s) was determined using an oxide solid-state electrochemical cell wherein calcia-stabilized-zirconia (CSZ) was used as an electrolyte. The standard molar Gibbs free energy of formation of Yb₂Ru₂O₇(s) and Yb₃RuO₇(s) from elements in their standard state was calculated by the least squares regression analysis of the data obtained in the present study and can be given respectively by: