Chitosan modified with terephthaloyl diazide as a drug delivery system

Russian Chemical Bulletin - pH- and thermo-sensitive hydrogels based on chitosan cross-linked with terephthaloyl diazide were synthesized. A new formulation of the polysaccharide modified with...     

Thermosensitive nanospheres with a gold layer revealed as low-cytotoxic drug vehicles

In this paper, the positive effect of a gold layer on cell viability is demonstrated by examining the results given by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfop henyl)-2H-tetrazolium (MTS) assay and two-color cell fluorescence viability (TCCV) assay. These cytotoxicity tests were performed with human cervical adenocarcinoma cells (HeLa cell line) and transformed African green monkey kidney fibroblast cells (Cos-7 cell line). To fabricate the nanostructures as drug vehicles, first, poly(l,l-lactide-co-ethylene glycol) (PLLA-PEG) and poly(N-isopropylacrylamide-co-D,D-lactide) (PNIPAAm-PDLA) were synthesized, and then two kinds of thermosensitive nanospheres comprising "shell-in-shell" structures without a gold layer (PLLA-PEG@PNIPAAm-PDLA) and with a gold layer (Au@PLLA-PEG@PNIPAAm-PDLA) were constructed by a modified double-emulsion method (MDEM). Both of them displayed a unique thermosensitive character exhibiting the lower critical solubility temperature (LCST) at 36.7 degrees C which was confirmed by UV-vis spectroscopy and differential scanning calorimetry (DSC). The release profiles of entrapped bovine serum albumin (BSA) were monitored at 22 and 37 degrees C, respectively, to reveal the thermal dependence on the release rate. In cell viability tests, both PLLA-PEG@PNIPAAm-PDLA and Au@PLLA-PEG@PNIPAAm-PDLA showed excellent cell viability, and furthermore, Au@PLLA-PEG@PNIPAAm-PDLA, particularly at high doses, exhibited more enhanced cell viability than PLLA-PEG@PNIPAAm-PDLA. This effect is mainly attributed to the gold layer which binds the protein molecules first and consequently facilitates transmembrane uptake of essential nutrients in the cell media, resulting in favorable cell proliferation.     

Chemical conjugation with cyclodextrins as a versatile tool for drug delivery

A pillar[5]arene-based N-heterocyclic carbene ligand was prepared by reaction of bromoethoxy pillar[5]arene with excess 1-methylimidazole at 130 °C in the absence of solvent and used as a catalyst for the Suzuki coupling reaction. Excellent yields were obtained when the Suzuki reactions were carried out under ambient atmosphere in ethanol, employing 0.2 mol% ligand, 1 mol% PdCl₂(CH₃CN)₂ and 1.5 mmol of K₂CO₃. The novel pillar[5]arene-based imidazolium salt is a promising material for the construction of highly active supramolecular catalytic systems.     

Polysaccharides as a source of advanced materials: Cellulose hollow microspheres for drug delivery in cancer therapy

Biocompatible hollow poly(methyl acrylic acid-co-N-isopropylacrylamide-co-ethyleneglycol dimethacrylate)@cellulose succinate (P(MAA-co-NIPAAM-co-EGDMA)@CS) microspheres have been synthesized by employing uniform silica-MPS microspheres as template. Silica spheres were synthesized via Stöber method involving tetraethyl orthosilicate. The surface of resulting silica Stöber microspheres was modified using 3-methacryloxypropyltrimethoxysilane (MPS), a polymerizable silane coupling agent. The above reagent introduces carbon–carbon double bonds on microspheres’ surface. This strategy uses the copolymerization of the following monomers, methacrylic acid (MAA), N-isopropyl acrylamide (NIPAAM) and the ethyleneglycol dimethacrylate (EGDMA), which was used as cross-linker, aiming at fabricating the first shell. Distillation precipitation polymerization method was carried out with 2,2-azobis(2-methylpropionitrile) as initiator in acetonitrile aiming at coating the inorganic microspheres with organic shell of the above-mentioned copolymer. In continuation, cellulose succinate and cellulose powder was absorbed through electrostatic interactions onto microspheres’ surface and the isolated product was cross-linked through esteric bonds formation. The cellulose succinate hollow microspheres were obtained after the silica core removal. The resulting spheres were characterized by Fourier transform infrared spectroscopy and observed by scanning and transmission electron microscopy. Dynamic light scattering was used to study the hydrodynamic diameter of the synthesized microspheres. The anticancer drug daunorubicin was loaded in the spheres, and its release behavior was evaluated at acidic and slightly basic pH conditions, aiming at evaluating its behavior at the healthy and pathogenic tissues.     

Intercalation compound of diclofenac sodium with layered inorganic compounds as a new drug material

The intercalation reaction of diclofenac sodium (DFS) with layered inorganic compounds, gamma-titanium phosphate (gamma-TiP), proton type titanium oxide (H-TiO2) and sodium type synthetic mica (Na-TSM), was examined on. The direct reaction of DFS in ethanol-water mixed solvent resulted in the large amount accommodation of DFS. The amount of intercalated DFS was the order of gamma-TiP>H-TiO2>Na-TSM corresponding to the order of acidity. The intercalation using phospholiopids was also examined to assist the intercalation reaction. However, the amount of intercalated DFS was rather small in comparison with those in the direct reaction. DFS accommodated in gamma-TiP dissolved into neutral and basic buffer solution stoichiometry while scarcely dissolved in the acidic solution. The mechanism of the intercalation and reverse dissolution was successfully accounted according to the ion-exchange mechanism between Na+ in DFS and H+ in gamma-TiP. The dissolution from tablet of DFS/gamma-TiP intercalation compound was examined by using a disintegrator. It was found that the dissolution rate appropriately controlled by mixing the disintegrator. The present results suggested the different possibilities in the clinical field to use layered inorganic compounds such as drug delivery system (DDS).     

Preparation and characterization of a novel magnetized nanosphere as a carrier system for drug delivery using Plantago ovata Forssk. hydrogel combined with mefenamic acid as the drug model

The aim of the present study was to magnetize Plantago ovata Forssk. hydrogel and produce a nanosphere system to carrier mefenamic acid as the drug model. For this propose, P. ovata seeds hydrogel (POSH) was extracted and magnetized by Fe₃O₄ being functionalized using tetraethyl orthosilicate and trimethoxyvinysilane. Thereafter, mefenamic acid (MFA) was loaded on the carrier system. The final product, as the magnetic drug loaded nanosphere (Fe/POSH/MFA), was fully characterized through different techniques involving X-ray diffraction (XRD), scanning electron microscopy (SEM), vibrating-sample magnetometer (VSM), thermal gravimetric analysis (TGA), dynamic light scattering (DLS), and FT-IR spectroscopy. The results confirmed the successful production of the drug loaded nanosphere system with particles magnetization of 25 emu/g over a range size of 40–50 nm. However, the size distribution less than 100 nm was measured through DLS analysis. The hydrogel showed a pH sensitivity swelling behavior representing the best efficacy at pH 7.4. The efficiency of the drug encapsulation was found to be 64.35%. The drug releasing was studied using a dialysis bag at pH = 7.4. The highest in vitro drug releasing was found to be 57.3 ± 0.6% after 72 h, as well. The findings of the current report account for the potential use of P. ovata hydrogel as an effective delivery system for encapsulation of water insoluble basic drugs, e.g., MFA in a magnetized carrier system.     

FeOOH-loaded mesoporous silica nanoparticles as a theranostic platform with pH-responsive MRI contrast enhancement and drug release

The development of stimuli-responsive theranostic platforms is of great demand for efficient cancer treatment because they can enhance diagnostic specificity and sensitivity.In this work,we report a p H-responsive theranostic nanoplatform based on Fe OOH clusters loaded mesoporous silica nanoparticles(Fe@MSNs).The as-synthesized Fe@MSNs possess activatable T_1magnetic resonance imaging(MRI)performance that can respond to the acidic microenvironment of solid tumor to turn on T_1singals by releasing paramagnetic Fe~(3+)ions.The Fe@MSNs are biocompatible without appreciable cytotoxicity.Moreover,the unique mesoporous structure endows the Fe@MSNs with significant advantages to effectively deliver chemotherapeutic drug for inhibiting the growth of solid tumor.We believe that this novel p H-responsive theranostic nanoplatform holds great promise in cancer treatment.     

Conjugation of pectin biopolymer with Au-nanoparticles as a drug delivery system: Experimental and DFT studies

In the present study, pectin-coated gold nanoparticles (GNPs) were used as a candidate for curcumin drug delivery. The effect of the size of synthesized GNPs was examined, as an important factor on the yield of drug delivery. For this purpose, three different sizes of GNPs were first synthesized using a chemical method. The synthesized nanoparticles were then coated with pectin biopolymer. Finally, curcumin drug was loaded in a pectin@GNPs complex. Various methods such as UV–vis spectrophotometry, dynamic light scattering, scanning electron microscopy and Fourier-transform infrared spectroscopy were used to characterize the synthesized GNPs and pectin@GNPs. The encapsulation efficiency and the release percentage of the drug were calculated for two different pH values. Further, an antibacterial study was conducted. The results revealed that 100 nm GNPs had the highest encapsulation efficiency. An investigation of the release rate of curcumin drug at 37°C for 48 h indicated that the amount of drug released was higher in acidic pH than at pH 7.4 with a slow release rate. The electronic structure and the adsorption properties of pectin–GNPs complex were examined using the density functional theory method.     

Preparation of a thermo- and pH-sensitive nanofibrous scaffold with embedded chitosan-based nanoparticles and its evaluation as a drug carrier

Environmentally sensitive poly(N-isopropylacrylamide) (PNIPAAm) nanofibrous scaffolds loaded with a hydrophilic drug were fabricated via an electrospinning process. First, thermally crosslinkable poly(NIPAAm-co-N-methylolacrylamide) (PNN) was synthesized by redox polymerization below the phase transition temperature of PNIPAAm. The phase transition temperature of the PNN copolymer could be altered from 34 to 40 °C by changing the ratio of N-methylolacrylamide (NMA) to NIPAAm. Subsequently, PNN/chitosan nanofibers were electrospun using ethanol/acetic acid/water as a cosolvent. The PNN/chitosan nanofibers were sensitive to both pH and temperature. The fibrous structure of the soaked PNN/chitosan nanofibers was successfully preserved by the crosslinking of NMA. Furthermore, the chitosan-based nanoparticles (NPs) were introduced into the PNN nanofibers (PNN/NPs) to achieve prolonged drug release. The nanoparticles were observed in the PNN nanofibers by transmission electron microscopy. All of the scaffolds examined had high tensile strengths (1.45 MPa or above) and exhibited no significant cytotoxicity toward human fetal skin fibroblasts. Finally, doxycycline hyclate was used as a model drug. The results illustrated that PNN/NPs nanofibrous scaffolds exhibited continuous drug release behavior for up to 1 week, depending on the pH and temperature.     

A [24-MC-6] zinc metallacoronate with a nonsteroidal antiinflammatory drug as the constructing ligand

The interaction of ZnCl(2) with 2-dipyridylketonoxime (=Hpko) and flufenamic acid (=Hfluf) in a basic methanolic solution leads to the formation of a hexanuclear 24-membered metallacoronate, [Zn(6)(OH)(2)(pko)(4)(fluf)(6)] (1), with a [Zn-O-C-O] repeat unit and a nonsteroidal antiinflammatory drug as the constructing ligand. Compound 1 retains its structure in a dimethyl sulfoxide solution, as shown by (1)H NMR spectroscopy and molar conductance.     

Simple surface functionalization of magnetic nanoparticles with methotrexate-conjugated bovine serum albumin as a biocompatible drug delivery vehicle

Magnetic nanoparticles (MNPs) functionalized with methotrexate (MTX)-conjugated bovine serum albumin (BSA) as a biocompatible drug delivery vehicle were synthesized using a facile method. Characterization of the functionalized MNPs (Fe₃O₄@BSA-MTX NPs) was performed using various techniques including UV–visible spectroscopy, dynamic light scattering, vibrating sample magnetometry and X-ray diffraction. The particle size and zeta potential of Fe₃O₄@BSA-MTX NPs were 105.7 ± 3.81 nm (mean ± SD) and −18.2 mV, respectively. MTX release from Fe₃O₄@BSA-MTX NPs showed an enzyme-dependent release pattern. Hemo-biocompatibility of Fe₃O₄@BSA-MTX NPs was confirmed using hemolysis test. In addition, the cytotoxicity of functionalized MNPs and free MTX against MCF-7 cell line was investigated using MTT assay. The results of experiments revealed that the Fe₃O₄@BSA-MTX NPs as a biocompatible carrier could improve the therapeutic effect of MTX.     

Coprecipitation with yttrium phosphate as a separation technique for iron(III), lead, and bismuth from cobalt, nickel, and copper matrices

The coprecipitation behavior of 44 elements (47 ions because of chromium(III,VI), arsenic(III,V), and antimony(III,V)) with yttrium phosphate was investigated at various pHs. Yttrium phosphate could quantitatively coprecipitate iron(III), lead, bismuth, and indium over a wide pH range; however, 18 ions, including alkali metals and oxo anions, such as vanadium(V), chromium(VI), molybdenum(VI), tungsten(VI), germanium(IV), arsenic(III,V), selenium(IV), and tellurium(VI), were scarcely collected. In addition, 19 ions, including cobalt, nickel, and copper(II), were hardly coprecipitated at pHs below about 3. Based on these results, the separation of iron(III), lead, and bismuth from cobalt, nickel, and copper(II) matrices was investigated. Iron(III), lead, and bismuth ranging from 0.5 to 25 μg could be separated effectively from a solution containing 0.5 g of cobalt, nickel, or copper at pH 3.0. The separated iron(III), lead, and bismuth could be determined by inductively coupled plasma atomic emission spectrometry using internal standardization. The detection limits (3σ, n = 7) of iron(III), lead, and bismuth were 0.008, 0.137, and 0.073 μg, respectively. The proposed method was applied to the analyses of metals and chlorides of cobalt, nickel, and copper.     

Structural features of mono- and tri-nuclear Zn(II) complexes with a non-steroidal anti-inflammatory drug as ligand

The interaction of Zn(II) with the non-steroidal anti-inflammatory drug tolfenamic acid leads to the formation of the structurally characterized trinuclear [Zn(3)(tolfenamato)(6)(CH(3)OH)(2)] complex. In the presence of the N,N'-donor heterocyclic ligands 1,10-phenanthroline and 2,2'-bipyridine at a range of ratios, the mononuclear Zn complexes of the general formulae [Zn(tolfenamato)(N,N'-donor)Cl] and [Zn(tolfenamato)(2)(N,N'-donor)] have been isolated and structurally characterized by X-ray crystallography. The deprotonated tolfenamato ligands are coordinated to the Zn(II) ion through carboxylato oxygen atoms. Tolfenamic acid and its complexes exhibit good binding propensity to human or bovine serum albumin protein having relatively high binding constant values.     

Biodegradable poly(ethylene carbonate) nanoparticles as a promising drug delivery system with "stealth" potential

The goal of this study was to investigate the suitability of poly(ethylene carbonate) (PEC) nanoparticles as a novel drug delivery system, fulfilling the requirements for a long circulation time. Particles were obtained with a narrow size distribution and nearly neutral zeta potential. Adsorption studies with human plasma proteins revealed that PEC nanoparticles bind much less proteins in comparison to polystyrene (PS) nanoparticles. Cell experiments with fluorescently labeled PEC showed no uptake of the nanoparticles by macrophages. These novel PEC nanospheres with their unique surface properties are a promising candidate for long circulating drug delivery systems in vivo.     

Acyclovir release from its composites with silica as a function of the silica matrix modification and the drug loading

Acyclovir release from its composites with unmodified silica at pH 1.6 and 7.4 follows zero order kinetics for two days. Modification of the silica matrix with phenyl groups leads to dramatic decrease in the drug release level at pH 7.4 compared with pH 1.6 as well as to heterogeneous phase state of acyclovir in the phenyl modified composite with high loading of the drug.     

Efficient isolation of carbonyl‐reducing enzymes using affinity approach with anticancer drug oracin as a specific ligand

Carbonyl‐reducing enzymes are important in both metabolism of endogenous substances and biotransformation of xenobiotics. Because sufficient amounts of native enzymes must be obtained to study their roles in metabolism, an efficient purification strategy is very important. Oracin (6‐[2‐(2‐hydroxyethyl)aminoethyl]‐5,11‐dioxo‐5,6‐dihydro‐11H‐indeno[1,2‐c] isoquinoline) is a prospective anticancer drug and one of the xenobiotic substrates for carbonyl‐reducing enzymes. A new purification strategy based on molecular recognition of carbonyl‐reducing enzymes with oracin as a ligand is reported here. The type of covalent bond, ligand molecules orientation, and their distance from the backbone of the solid matrix for good stearic accessibility were taken into account during the designing of the carrier. The carriers based on magnetically active microparticles were tested by recombinant enzymes AKR1C3 and CBR1. The SiMAG‐COOH magnetic microparticles with N‐alkylated oracin and BAPA as spacer arm provide required parameters: proper selectivity and specificity enabling to isolate the target enzyme in sufficient quantity, purity, and activity.