Improve Solubility and Bioavailability of Silver Sulfadiazine via Formation of Inclusion Complex by Cyclodextrin

Supramolecular nanocontainers of cyclodextrins (α-CD or β-CD)/silver sulfadiazine (SSD) were prepared by inclusion complex (IC) forming between CDs and SSD at various conditions (at room temperature and under sonic energy). Obtained nanocontainers were characterized by XRD, SEM, EDX and FTIR. Formation of inclusion complex was confirmed via significant differences between FTIR and XRD spectra of pure compounds with respect to those of the complexes. EDX analysis indicated the homogenous distribution of Ag nanoparticles in the nanocontainers. Solubility, bioavailability and in vitro dissolution of obtained SSD nanocontainers were compared with pure SSD and results show that by encapsulation of SSD, solubility improved and its release is controllable. Solubility and bioavailability of β-CD/SSD is higher than α-CD/SSD, which is related bigger β-CD cavity that can entrap a higher number of SSD molecules.     

Anticorrosion behavior of cyclodextrins/inhibitor nanocapsule-based self-healing coatings

The self-healing anticorrosion property of coating containing cyclodextrins/inhibitor nanocontainers was investigated by SEM, TEM, salt spray, and EIS measurements. The influences of cyclodextrin type (α-CD, β-CD and γ-CD) and nanocapsules diameter on the anticorrosive performance of the scratched samples were studied under salt spray conditions, which revealed that the coatings containing γ-CD/inhibitor nanocontainers with larger nanocapsules at room temperature demonstrated the best anticorrosion behavior. Inclusion complex formation of MBI or MBT with CDs led to encapsulated corrosion inhibitors which became active in corrosive electrolytes, and could slowly diffuse out of the host material to ensure continuous delivery of the inhibitors to corrosion sites and long-term corrosion protection. Additionally, the kinetics of the self-healing process characterized by EIS measurement was parametrically analyzed in an equivalent circuit when the coating was exposed to salt solution.     

Epoxy coating with self-healing capability based on a 2-mercaptobenzothiazole-loaded CeO2 nanocontainer

In this study, we demonstrated a facile approach for the synthesis of nanocontainers using the encapsulation of a 2-mercaptobenzothiazole (MBT) inhibitor; these nanocontainers were capable of responsively releasing a corrosion inhibitor and of self-healing performances. The anticorrosive performance of the CeO₂ nanocontainers was investigated with electrochemical impedance spectroscopy (EIS) measurement in a saline electrolyte via the incorporation of different weight percentages (0.5, 1, and 2 wt %) of synthesized nanocontainer in epoxy (EP) resin. The EIS results show that the loading of 1 wt % CeO₂ nanocontainer containing MBT inhibitor in the epoxy (EP) coating [EP/NC MBT–CeO₂ (1%)] provided the highest R_coat, the lowest constant phase element of coating, and the optimum release of MBT at different operating pHs. The highest coating resistance R_coat values of this coating (7.81 × 10⁷ Ω cm²) were about 12 and 8573 times greater than those considered for EP–CeO₂ and EP coatings, respectively. Different releases of the MBT inhibitor were detected at various pHs. We found that the coating operating in acidic media exhibited a better self-healing performance. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47297.     

Role of intermolecular interaction between hydrophobic blocks in block-selected inclusion complexation of amphiphilic poly(ethylene oxide)-poly[(R)-3-hydroxybutyrate]-poly(ethylene oxide) triblock copolymers with cyclodextrins

The influence of hydrophobic interaction between poly[(R)-3-hydroxybutyrate] blocks on block-selected inclusion complexation between amphiphilic poly(ethylene oxide)-poly[(R)-3-hydroxybutyrate]-poly(ethylene oxide)) (PEO-PHB-PEO) triblock copolymers and α-cyclodextrin (α-CD) or γ-cyclodextrin (γ-CD) was studied by X-ray diffraction, differential scanning calorimetry (DSC), FTIR and ¹H NMR. Due to the stronger hydrophobic interaction at higher temperature, the amphiphilic triblock copolymer tends to aggregate to form tighter core-shell sphere with PHB block in the core and PEO in the corona. Therefore, the CD threaded onto PEO blocks cannot further slide onto the PHB block, which resulted in a highly block-selected inclusion complex formation. Moreover, the DSC results indicated that the triblock copolymer coalesced from its ICs with hot water showed an increase in microphase separation compared with the as-synthesized triblock copolymer, which further supports our hypothesis that CD only selectively includes PEO blocks of the triblock copolymer at higher temperature.     

Synthesis and Characterization of the Inclusion Complex of Dicationic Ionic Liquid and β-Cyclodextrin

The supramolecular structure of the inclusion complex of β-cyclodextrin (β-CD) with 1,1',2,2'-tetramethyl-3,3'-(p-phenylenedimethylene) diimidazolium dibromide (TetraPhimBr), a dicationic ionic liquid, has been investigated. The inclusion complex with 1:1 molar ratio was prepared by a kneading method. Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction (XRD) analysis, (1)H NMR and thermogravimetric analysis (TGA) confirmed the formation of the inclusion complex. The results showed that the host-guest system is a fine crystalline powder. The decomposition temperature of the inclusion complex is lower than that of its parent molecules, TetraPhimBr and β-CD individually.     

Antibacterial activity of PVA-based nanofibers loaded with silver sulfadiazine/cyclodextrin nanocapsules

Silver sulfadiazine (SSD) is a highly insoluble drug in water with a significant antibacterial activity. Supramolecular nanocontainers of cyclodextrins (β-CD or HPβ-CD)/SSD were prepared by inclusion complex (IC) forming between CDs and SSD at various conditions. Solubility, bioavailability and in vitro dissolution of obtaining SSD were investigated and the results showed of SSD in CDs that solubility improved and its release is controllable by encapsulation cavity. Electro-spun nanofibers of PVA containing SSD/CDs inclusion complex showed significant antibacterial effect against Escherichia coli and Staphylococcus aureus, which are related to SSD     

Preparation and Characterization of Inclusion Complexes of Poly(dimethylsiloxane)s with <Emphasis Type="Bold">γ</Emphasis>-Cyclodextrin Without Utilizing Sonic Energy

cyclodextrin (-CD) formed inclusion complexes with poly(dimethylsiloxane)s (PDMS) under sonic energy and the products were crystalline compounds. In this study an inclusion complex between PDMS and -CD was synthesized at room temperature in the presence of light and mixing, in the absence of light and in the absence of mixing. These inclusion complexes (ICs) were characterized by XRD, DSC, ¹H NMR, UV–Vis and FT-IR spectroscopy. The findings suggest that the reaction conditions change the crystalline structure and mole ratios of the complexes (monomer unit/-CD) determined by ¹H NMR spectroscopy for all of the ICs with -CD; which is 2 at room temperature, 1.5 under sonic energy, 3 without light and mixing. The UV–Vis results indicate an IC between -CD and PDMS.     

Conventional Study on Novel Dicationic Ionic Liquid Inclusion with β-Cyclodextrin

This study focuses on the synthesis and characterization of the inclusion complex of β-Cyclodextrin (β-CD) with dicationic ionic liquid, 3,3'-(1,4-Phenylenebis [methylene]) bis(1-methyl-1H-imidazol-3-ium) di(bromide) (PhenmimBr). The inclusion complex was prepared at room temperature utilizing conventional kneading technique. Proton ((1)H) NMR and 2D ((1)H-(1)H) COSY NMR were the primary characterization tools employed to verify the formation of the inclusion complex. COSY spectra showed strong correlations between protons of imidazolium and protons of β-CD which indicates that the imidazolium ring of PhenmimBr has entered the cavity of β-CD. UV absorption indicated that β-CD reacts with PhenmimBr to form a 2:1 β-CD-PhenmimBr complex with an apparent formation constant of 2.61 × 10(5) mol&(-2) L(2). Other characterization studies such as UV, FT-IR, XRD, TGA, DSC and SEM studies were also used to further support the formation of the β-CD-PhenmimBr inclusion complex.     

Enhanced thermal properties of PS nanocomposites formed from montmorillonite treated with a surfactant/cyclodextrin inclusion complex

We have prepared polystyrene/clay nanocomposites using an emulsion polymerization technique. The nanocomposites were exfoliated at 3 wt% content of pristine clay relative to the amount of polystyrene (PS). We employed two surfactants for the montmorillonite: cetylpyridinium chloride (CPC) and the CPC/α-CD inclusion complex. Prior to polymerization, each surfactant intercalates into the layers of the pristine clay dispersed in water. The inclusion complex was characterized by X-ray diffraction, ¹³C CP/MAS NMR spectra, and ¹H NMR spectroscopy, and TGA. X-ray powder patterns of the CPC/α-CD complex indicate that the α-CDs units form channels. The ¹³C CP/MAS NMR spectrum of the complex suggests that a CPC chain is included in the channel formed by the α-CDs. The ¹H NMR spectra of the complexes indicate that the stoichiometry of the complexes is 1:2 (i.e. one CPC molecule and two α-CD units). The TGA reveals that the inclusion complex has higher thermal stability relative to the virgin CPC. We employed both X-ray diffraction (XRD) and transmission electron microscopy (TEM) to characterize the structures of the nanocomposites. The value of T_g of the PS component in the nanocomposite is 6 °C higher than that of the virgin PS and its thermal decomposition temperature is 33 °C higher. The CPC/α-CD-treated clay is more effective than is virgin CPC-treated clay at enhancing the thermal stability of polystyrene.     

青藤碱与羟丙基-β-环糊精的包合作用

通过溶液共混法制备青藤碱-羟丙基-β-环糊精包合物,纯化后利用体视显微镜观察包合物的结晶形态,通过差热示重扫描、红外光谱、X射线粉末衍射及核磁共振波谱等方法对包合物进行性质分析,并通过相溶解度法计算包合物的包合常数。结果表明,青藤碱、羟丙基-β-环糊精包合后性质发生明显变化,羟丙基-β-环糊精能显著增加青藤碱的溶解度,包合物中青藤碱与羟丙基-β-环糊精包合分子个数比为1∶1,其包合常数为150.0 L/mol,反应的吉布斯自由能为-12.41 kJ/mol。     

Poly(ε-caprolactone) electrospun nanofibers containing curcumin nanocontainers: enhanced solubility,dissolution and physical stability of curcumin via formation of inclusion complex with cyclodextrins

Supramolecular nanocontainers of cyclodextrins (α- and β-CD)/curcumin (CUR) were prepared by inclusion complex (IC) forming between CDs and guest molecule at two conditions. Formation of the inclusion complex between CDs and CUR at various conditions in solid phase was characterized by various methods. Solubility and in vitro dissolution of obtaining CUR nanocapsules were investigated and results showed that encapsulation of CUR, improved CUR bioavailability with a controllable release. Electrospun nanofibers of poly-ε-caprolactone (PCL) containing CUR/CDs inclusion complex of various conditions have been fabricated using a conventional electrospinning process and indicated that these nanofibers are bead-free.     

Synthesis and controlled release of curcumin-β-cyclodextrin inclusion complex from nanocomposite poly(N-isopropylacrylamide/sodium alginate) hydrogels

Inclusion complex of curcumin with β-cyclodextrin (Cur-β-CD) was prepared using coprecipitation method. Stoichiometric ratio between curcumin and β-cyclodextrin was found to be 1:2 with an association constant of 3.80 × 10⁸ M⁻² using Benesi–Hildebrand method. Inclusion complex formation was confirmed by FTIR and DSC analyses. Water solubility of curcumin increased from 0.00122 to 0.721 mg mL⁻¹ with the inclusion complex formation. Release of the inclusion complex from the nanocomposite and conventional poly(N-isopropylacrylamide/sodium alginate hydrogels crosslinked by nanoclay and N,N′-methylenebis(acrylamide) (BIS), respectively, were investigated in simulated gastrointestinal conditions. Swelling ratio and cumulative release were dependent on the hydrogel composition and pH. At pH = 1.2, hydrogels showed the lowest release ratio, but at pH = 6.8 highest swelling ratios were attained. The swelling ratio and cumulative release decreased with increasing the nanoclay content in nanocomposite hydrogels. On the contrary, as the ratio of BIS in the conventional hydrogels increased, the swelling ratio and cumulative release increased. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47554.     

Comparative electrochemical study of self-assembled monolayers of 2-mercaptobenzoxazole, 2-mercaptobenzothiazole, and 2-mercaptobenzimidazole formed on polycrystalline gold electrode

Comparative electrochemical behavior of self-assembled monolayers (SAMs) of three heteroaromatic thiols, 2-mercaptobenzoxazole (MBO), 2-mercaptobenzothiazole (MBT), and 2-mercaptobenzimidazole (MBI) are investigated by means of cyclic voltammetry and electrochemical impedance spectroscopy (EIS). The electrochemical characteristics of the electrode/solution interface are considerably and differently affected by thiols constructing the SAMs. The consumed charges for reductive desorption of SAMs, which is criterion for the amount of chemically adsorbed thiol, are significantly different for these three SAMs, specially for MBT, implying that SAM of MBT is formed through both sulfur atoms; the thiol sulfur and skeleton sulfur of the thiazole ring. Desorption potentials of the SAMs have shown the following order for strength of gold-sulfur bond: MBT > MBO > MBI. Activity of the three SAMs as pH-sensitive interfaces was also investigated and their surface-pK_a values derived from the EIS measurements showed this order for acidic strength of SAMs: MBO > MBT > MBI. This is the same order expected due to the difference in electronegativity of the O, S, and N heteroatoms, and confirms that the most electron-rich ring imidazole is attached to the benzene ring of MBI. A comparison of the interfacial charge transfer resistance variation as a function of gold immersion time in thiols solution reveals that kinetics of Au-MBT assembly is different from those of two others and confirms formation of Au-MBT SAM via both sulfur atoms of MBT.     

Experimental and Theoretical Investigations on the Supermolecular Structure of Isoliquiritigenin and 6-O-α-d-Maltosyl-β-cyclodextrin Inclusion Complex

Isoliquiritigenin (ILTG) possesses many pharmacological properties. However, its poor solubility and stability in water hinders its wide applications. The solubility of bioactive compounds can often be enhanced through preparation and delivery of various cyclodextrin (CD) inclusion complexes. The 6-O-α-d-maltosyl-β-CD (G₂-β-CD), as one of the newest developments of CDs, has high aqueous solubility and low toxicity, especially stable inclusion characteristics with bioactive compounds. In this work, we for the first time construct and characterize the supermolecular structure of ILTG/G₂-β-CD by scanning electron microscopy (SEM), ultraviolet-visible spectroscopy (UV), Fourier transform infrared spectroscopy (FT-IR), and X-ray diffractometry (XRD). The solubility of ILTG in water at 25 °C rises from 0.003 to 0.717 mg/mL by the encapsulation with G₂-β-CD. Our experimental observations on the presence of the ILTG/G₂-β-CD inclusion complex are further supported by the ONIOM(our Own N-layer Integrated Orbital molecular Mechanics)-based QM/MM (Quantum Mechanics/Molecular Mechanics) calculations, typically substantiating these supermolecular characteristics, such as detailed structural assignments, preferred binding orientations, selectivity, solvent effects, interaction energies and forces of the ILTG/G₂-β-CD inclusion complex. Our results have elucidated how ILTG interacts with G₂-β-CD, demonstrating the primary host-guest interactions between ILTG and G₂-β-CD, characterized by hydrogen bonds, hydrophobic interactions, electrostatic forces, and conformational effects, are favored for the formation of the ILTG/G₂-β-CD inclusion.     

Formation of the crystalline inclusion complex between γ-cyclodextrin and poly(N-acetylethylenimine)

Poly(N-acetylethylenimine) was found to form a crystalline inclusion complex with γ-cyclodextrin (CD). It did not form crystalline inclusion complexes with α-CD or β-CD. It is a hydrophilic, nitrogen atom-containing polymer that forms a crystalline inclusion complex with CD. FT-IR spectroscopy, thermogravimetry analysis, X-ray diffraction, ¹H NMR spectra and ¹³C CP/MAS NMR spectra were used to characterize the structure and property of the crystalline inclusion complex.     

Inclusion complexes of atorvastatin calcium (ATV-Ca) and rosuvastatin calcium (ROV-Ca) drugs with α-CD, β-CD, γ-CD,HP-β-CD,M-β-CD,and maltodextrin along with their characterizations through experimental and computational methods

The aim of this research is a comparison of the efficiency of six commercially available cyclodextrins (CDs) to improve the solubility and oral bioavailability of atorvastatin calcium (ATV-Ca) and rosuvastatin calcium (ROV-Ca) drugs in aqueous media. Inclusion complexes of both drugs with non-toxic α-CD, β-CD, γ-CD, HP-β-CD, M-β-CD, and maltodextrin were prepared in a 1:1 stoichiometry via the kneading method. To reach the best CD, various experimental and computational analyses were performed including phase solubility, dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), atomic force microscopy (AFM), hydrogen-1 nuclear magnetic resonance (¹HNMR), carbon-13 nuclear magnetic resonance (¹³CNMR), and molecular docking calculations. The M-β-CD turned out to be the best substrate for the micro-encapsulation of both drugs. Also, ATV showed a higher tendency than ROV to form inclusion complexes with CDs. Molecular docking studies showed that HP–β–CD and M-β-CD are the most suitable substrates for the formation of inclusion complexes, respectively. Our research showed that the β-CD is not necessarily the most efficient substrate for increasing solubility based on previous reports in the literature; meanwhile, the other employed substrates in this study can show acceptable performances in this regard. According to our results, M-β-CD is the best substrate for the micro-encapsulation of both drugs, which increases their solubility in water.     

Synthesis and Characterization of the Inclusion Complex of β-cyclodextrin and Azomethine

A β-cyclodextrin (β-Cyd) inclusion complex containing azomethine as a guest was prepared by kneading method with aliquot addition of ethanol. The product was characterized by Fourier Transform Infrared (FTIR) spectrometer, ¹H Nuclear Magnetic Resonance (¹H NMR) and Thermogravimetric Analyzer (TGA), which proves the formation of the inclusion complex where the benzyl part of azomethine has been encapsulated by the hydrophobic cavity of β-Cyd. The interaction of β-Cyd and azomethine was also analyzed by means of spectrometry by UV-Vis spectrophotometer to determine the formation constant. The formation constant was calculated by using a modified Benesi-Hildebrand equation at 25 °C. The apparent formation constant obtained was 1.29 × 10⁴ L/mol. Besides that, the stoichiometry ratio was also determined to be 1:1 for the inclusion complex of β-Cyd with azomethine.     

Synergistic effect of 2-mercapto benzimidazole and KI on copper corrosion inhibition in aerated sulfuric acid solution

2-Mercapto benzimidazole (MBI) was used as a copper corrosion inhibitor in aerated 0.5 mol L^–1 H₂SO₄ solutions. The inhibition efficiency (IE) increased with increasing MBI concentration to 74.2% at the 1 mM level. A synergistic effect existed when MBI and iodide ions were used together to prevent copper corrosion in sulfuric acid. It was found that IE reached 95.3% in 0.5 mol L^–1 H₂SO₄ solutions containing 0.75 mmol L^–1 MBI and 0.25 mmol L^–1 KI. X-ray photoelectron spectroscopy (XPS) analysis of the copper samples showed that a (Cu⁺MBI) complex film formed on the surface to inhibit the copper corrosion and the iodide ions did not participate in the formation of the inhibitor film. The synergistic effect was attributed to the adsorption of iodide anions on the copper surface, which then facilitated the adsorption of protonated MBI and the formation of an inhibitive film.     

Preparation, characterization and novel photoregulated rheological properties of azobenzene functionalized cellulose derivatives and their α-CD complexes

Novel azobenzene functionalized hydroxypropyl methylcellulose (AZO-HPMC) polymers and their α-CD (α-Cyclodextrin) complexes have been prepared. FT-IR, ¹H NMR and FT-Raman spectroscopy confirm the existence of azobenzene chromophores in AZO-HPMC polymers. α-CD can improve the water solubility of AZO-HPMC by formation of inclusion complexes with azobenzene side groups. Rheological studies substantiate that both AZO-HPMC and its α-CD complex undergo thermoreversible sol-gel transitions in aqueous solutions. Viscometric measurements suggest that the association between azobenzene side groups can be eliminated by α-CD. The effect of photoirradiation on the rheological behavior shows that the gelation temperature of AZO-HPMC increases after UV irradiation, while the gelation temperature of AZO-HPMC/α-CD complex decreases after UV irradiation.     

β-Cyclodextrin Inclusion Complex to Improve Physicochemical Properties of Pipemidic Acid: Characterization and Bioactivity Evaluation

The aptitude of cyclodextrins (CDs) to form host-guest complexes has prompted an increase in the development of new drug formulations. In this study, the inclusion complexes of pipemidic acid (HPPA), a therapeutic agent for urinary tract infections, with native β-CD were prepared in solid state by kneading method and confirmed by FT-IR and ¹H NMR. The inclusion complex formation was also characterized in aqueous solution at different pH via UV-Vis titration and phase solubility studies obtaining the stability constant. The 1:1 stoichiometry was established by a Job plot and the inclusion mechanism was clarified using docking experiments. Finally, the antibacterial activity of HPPA and its inclusion complex was tested on P. aeruginosa, E. coli and S. aureus to determine the respective EC_50s and EC_90s. The results showed that the antibacterial activity of HPPA:β-CD against E. coli and S. aureus is higher than that of HPPA. Furthermore, HPPA and HPPA:β-CD, tested on human hepatoblastoma HepG2 and MCF-7 cell lines by MTT assay, exhibited, for the first time, antitumor activities, and the complex revealed a higher activity than that of HPPA. The use of β-CD allows an increase in the aqueous solubility of the drug, its bioavailability and then its bioactivity.