Electrospinning of cyclodextrin functionalized polyethylene oxide (PEO) nanofibers

By means of the electrospinning technique we have successfully synthesized cyclodextrin (CD) functionalized polyethylene oxide (PEO) nanofibers (PEO/CD) with the ultimate goal to develop functional nanowebs. Three different types of CDs; α-CD, β-CD and γ-CD are incorporated individually in electrospun PEO nanofibers. The aqueous solutions containing different amount of PEO (3%, 3.5% and 4% (w/v), with respect to solvent) and CDs (25% and 50% (w/w), with respect to PEO) are electrospun and bead-free nanofibers are obtained. The presence of the CDs in the PEO solutions is found to facilitate the electrospinning of bead-free nanofibers from the lower polymer concentrations and this behavior is attributed to the high conductivity and viscosity of the PEO/CD solutions. The presence of CDs in the electrospun PEO nanofibers is confirmed by Fourier transform infrared (FTIR) spectroscopy studies. The 2-D X-ray diffraction (XRD) spectra of PEO/CD nanowebs did not show any significant diffraction peaks for CDs indicating that the CD molecules are distributed within the polymer matrix without any phase separated crystalline aggregates.     

虫草素与羟丙基-β-环糊精的包合行为及性能研究

通过饱和溶液方法制备了虫草素(COR)与羟丙基-β-环糊精(HPβCD)形成的包合物.采用紫外-可见光谱法对水溶液中HPβCD与虫草素(COR)的包合行为进行研究,利用Job曲线法确定COR/HPβCD包合物的包合比,通过1 H NMR和2D NMR、DSC、TG、XRD、FTIR和SEM对COR/HPβCD包合物进行表征和性能测定.结果表明,COR/HPβCD包合物的包合比为1:1,虫草素与HPβCD形成包合物后,其水溶性、热稳定性及生物环境稳定性都得到明显提高.COR/HPβCD包合物在医药领域具有潜在的应用前景.     

Cyclodextrin-surfactant coassembly depends on the cyclodextrin ability to crystallize

Full equilibrium phase diagrams are presented for two ternary systems composed of the cationic surfactant dodecyltrimethylammonium bromide (DTAB), water (D(2)O), and a cyclodextrin, either β-cyclodextrin (β-CD) or (2-hydroypropyl)-β-cyclodextrin (2HPβCD). (2)H NMR, SAXS, WAXS, and visual examination were used to determine the phase boundaries and characterize the nature of the phases formed. Additionally, diffusion (1)H NMR was used to investigate parts of the diagrams. The water solubility of 2HPβCD is 80% (w/w), whereas it is only 1.85% (w/w) for β-CD. Solubility increases for both species upon complexation with DTAB; while the increase is minute for 2HPβCD, it is dramatic for β-CD. Both systems displayed an isotropic liquid solution (L(1)) one-phase region, the extension of which differs extensively between the two systems. Additionally, the DTAB:2HPβCD:water system also comprised a normal hexagonal (H(1)) area, which was not found for the DTAB:β-CD:water system. In the DTAB:β-CD:water system, on the other hand, we found cocrystallization of DTAB and β-CD. From this work we conclude that DTAB and CD molecules form 1:1 inclusion complexes with high affinities. Moreover, we observed indications of an association of 2HPβCD to DTAB micelles in the isotropic solution phase, which was not the case for β-CD and DTAB micelles. This is, to our knowledge, the first complete phase diagrams of surfactant-CD mixtures; as a novel feature it includes the observation of cocrystallization at high concentrations.     

Preparation and characterization of poly(ethylene oxide)‐loaded hydroxypropyl‐β‐cyclodextrin nanofibers

Hydroxypropyl‐β‐cyclodextrin (HP‐β‐CD) is a modified β‐cyclodextrin (β‐CD) derivative, which is toxicologically harmless to mammals and other animals. HP‐β‐CD is electrospun from an aqueous solution by blending with a non‐toxic, biocompatible, synthetic polymer poly(ethylene oxide) (PEO). Aqueous solutions containing different HP‐β‐CD/PEO blends (50:50–80:20) with variable concentrations (4 wt%–12 wt%) were used. Scanning electron microscope was used to investigate the morphology of the fibers, and Fourier transform infrared spectroscopy analysis confirmed the presence of HP‐β‐CD in the fiber. Uniform nanofibers with an average diameter of 264, 244, and 236 nm were obtained from 8 wt% solution of 50:50, 60:40, and 70:30 HP‐β‐CD/PEO, respectively. The average diameter of the fiber was decreased with increasing of HP‐β‐CD/PEO ratio. However, a higher proportion of HP‐β‐CD in the spinning solution increased beads in the fibers. The polymer concentration had no significant effect on the fiber diameter. The most uniform fibers with the narrowest diameter distribution were obtained from the 8 wt% of 50:50 solution. Copyright © 2015 John Wiley & Sons, Ltd.     

Binary and ternary inclusion complexes of dapsone in cyclodextrins and polymers: preparation, characterization and evaluation

Dapsone (DAP) is a synthetic sulfone drug with bacteriostatic activity, mainly against Mycobacterium leprae. In this study we have investigated the interactions of DAP with cyclodextrins, 2-hydroxypropyl-β-cyclodextrin (HPβCD) and β-cyclodextrin (βCD), in the presence and absence of water-soluble polymers, in order to improve its solubility and bioavailability. Solid systems DAP/HPβCD and DAP/βCD, in the presence or absence of polyvinylpyrrolidone (PVP K30) or hydroxypropyl methylcellulose (HPMC), were prepared. The binary and ternary systems were evaluated and characterized by SEM, DSC, XRD and NMR analysis as well as phase solubility assays, in order to investigate the interactions between DAP and the excipients in aqueous solution. This study revealed that inclusion complexes of DAP and cyclodextrins (HPβCD and βCD) can be produced in order to improve DAP solubility and bioavailability in the presence or absence of polymers (PVP K30 and HPMC). The more stable inclusion complex was obtained with HPβCD, and consequently HPβCD was more efficient in improving DAP solubility than βCD, and the addition of polymers had no influence on DAP solubility or on the stability of the DAP/CDs complexes.     

Thermodynamic and geometric study of diasteroisomeric complexes formed by racemic flavanones and three cyclodextrins through NMR

The main purpose of this work was to study the chiral recognition thermodynamics of inclusion complexes formed by flavanones and β-cyclodextrins, and its relation with the inclusion geometries, through NMR experiments. By using the racemic mixtures of (±)-flavanone (FL) and (±)-2′-hydroxyflavanone (2′OHFL), diasteroisomeric complexes were formed employing β-cyclodextrin (βCD), (2-hydroxypropil)-β-cyclodextrin (HPβCD) and heptakis-(2,6-O-dimethyl)-β-cyclodextrin (DMβCD). ¹H NMR experiments of the complexes showed enantiodifferentiation for FL/βCD, FL/HPβCD, FL/DMβCD, 2′OHFL/HPβCD and 2′OHFL/DMβCD complexes, so they were able to be studied by obtaining the stoichiometry (1:1 for each complex), association constants (Ka), Ka ratios, and thermodynamics (ΔH, ΔS and ΔG). The results show that Ka values decrease with increasing temperature and that Ka ratio values removed from 1 not always reflect better enantiodiscrimination by NMR. Thermodynamics (ΔH and ΔG) show an exothermic and spontaneous formation of the complexes. Since the results were established for each couple of diasteroisomeric complexes separately, comparison of thermodynamics between them was possible, concluding that one half of the couples of diasteroisomeric complexes present chiral recognition due to enthalpic phenomena and the other half due to entropic phenomena. Additionally, ROESY experiments were performed to estimate the inclusion geometry of the complexes, which are in good agreement with the thermodynamic and Ka results.     

Complexation of capsaicin with β-cyclodextrins to improve pesticide formulations: effect on aqueous solubility, dissolution rate, stability and soil adsorption

The binary systems of capsaicin (CP) and β-cyclodextrin (βCD) or hydroxypropyl-β-cyclodextrin (HPβCD) were investigated in an attempt to improve formulations of this pesticide. UV spectral shift methods indicated guest–host complex formation between CP and the two cyclodextrins (CDs). Phase solubility analysis showed B_s type diagrams with βCD, A_L type with HPβCD indicating the formation of an inclusion complex at 1:1 stoichiometric ratio in solution state. Solubility profiles indicated a 50-fold enhancement of CP solubility could be achieved in the presence of 60 mM HPβCD with respect to CP alone. Solid co-evaporated systems (CES) with 1:0.5–1:5 molar ratios of CP/CDs were physicochemically characterized, revealing that the true inclusion complexes could be formed in the solid CP/βCD systems with 1:5 molar ratio and in the solid CP/HPβCD systems with the molar ratios more than 1:3, respectively. In contrast, crystalline drug was detectable in all other systems. Compared with corresponding physical mixtures (PMs), the CES exhibited significant enhancement with regard to CP dissolution and the protection from CP degradation under the accelerated conditions. It was also revealed that complexation of CP with HPβCD had a pronounced improved effect on the pesticide formulations and greatly reduced the amount of CP adsorbed in the soil. These results demonstrate that HPβCD may be a preferred excipient, enabling more efficient and intelligent use of CP/CDs inclusion complexes in the development of pesticide formulations.     

Influence of solvents on the formation of ultrathin uniform poly(vinyl pyrrolidone) nanofibers with electrospinning

Although there have been many reports on the preparation and applications of various polymer nanofibers with the electrospinning technique, the understanding of synthetic parameters in electrospinning remains limited. In this article, we investigate experimentally the influence of solvents on the morphology of the poly(vinyl pyrrolidone) (PVP) micro/nanofibers prepared by electrospinning PVP solution in different solvents, including ethanol, dichloromethane (MC) and N,N‐dimethylformamide (DMF). Using 4 wt % PVP solutions, the PVP fibers prepared from MC and DMF solvents had a shape like a bead‐on‐a‐string. In contrast, smooth PVP nanofibers were obtained with ethanol as a solvent although the size distribution of the fibers was somewhat broadened. In an effort to prepare PVP nanofibers with small diameters and narrow size distributions, we developed a strategy of using mixed solvents. The experimental results showed that when the ratio of DMF to ethanol was 50:50 (w/w), regular cylindrical PVP nanofibers with a diameter of 20 nm were successfully prepared. The formation of these thinnest nanofibers could be attributed to the combined effects of ethanol and DMF solvents that optimize the solution viscosity and charge density of the polymer jet. In addition, an interesting helical‐shaped fiber was obtained from 20 wt % PVP solution in a 50:50 (w/w) mixed ethanol/DMF solvent. © 2004 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 42: 3721–3726, 2004     

Preclinical pharmacokinetics comparison between resveratrol 2-hydroxypropyl-β-cyclodextrin complex and resveratrol suspension after oral administration

Trans-Resveratrol (RV) is a natural polyphenol characterized by interesting pleiotropic potentials and health benefits, but its administration is hampered by a unsatisfactory pharmacokinetics. Various approaches have been identified to circumvent it: among them, 2-hydroxypropyl-β-cyclodextrins (HPβCD) are valuable strategy. Here, we compare the employment of HPβCD based formulation with a resveratrol nanosupension (obtained by diluting a RV ethanol solution with PBS, added of 0.05 % hydroxyethylcellulose) to improve RV bioavailability after oral administration to mice. The inclusion of RV in HPβCD was confirmed by differential scanning calorimetry, Fourier transformed infrared spectroscopy, and phase solubility study. The two formulations were orally administered to BALB-c mice. RV concentrations in plasma and tissues were detected at different time (0–120 min) by HPLC method. HPβCD complexation mediate a approximately fourfold increment in plasma RV C_max and  approximately twofold augment of RV AUC_0-120 in comparison with RV nanosuspension. Similar increased concentrations were observed in heart, liver, kidney and gut. In particular, HPβCD mediated a 5.5-folds increase of resveratrol concentration in the intestine, in comparison to the nanosuspension. In conclusion, based on our results, HPβCD complexation is a promising approach to increase the oral bioavailability of RV. Moreover, the achievement of high concentrations in gut suggested a potential employment of oral RV-HPβCD as anti-inflammatory/chemopreventive agent in this tissue.     

Characterization of gelatin nanofibers electrospun using ethanol/formic acid/water as a solvent

Gelatin nanofibers were prepared via electrospinning using aqueous solutions of formic acid and ethanol as the solvent instead of cytotoxic solvents. The resulting mat was further crosslinked with glutaraldehyde (GTA). The influence of the storing time on the viscosity and gel point of the solution was investigated. The gelatin nanofibers were examined using a field emission scanning electron microscope (FESEM) for the fiber size and morphology. The lowest diameter of gelatin fiber (85 nm, without beads) was achieved when the gelatin concentration was 20 wt% and electrospinning was conducted with a voltage of 20 kV over a distance of 10 cm at ambient temperature. The results from differential scanning calorimetry (DSC) showed that the softening temperature of gelatin nanofibers crosslinked with GTA was elevated. In addition, GTA‐crosslinked gelatin nanofibers exhibited cell compatibility for mouse mesangial cells (CRL 1927). Copyright © 2008 John Wiley & Sons, Ltd.     

Photostability Study of Doxorubicin Aqueous Solution Enhanced by Inclusion Interaction between Doxorubicin and Hydroxypropyl-β-cyclodextrin

The photodegradation of doxorubicin (Dox) in the presence of hydroxypropyl‐β‐cyclodextrin (HP‐β‐CD) was studied; the degradation rate constant in the presence of HP‐β‐CD estimated by Lineweaver‐Burk analysis was approximately three times lower than that of free Dox aqueous solution, which shows that HP‐β‐CD can enhance the photostability of doxorubicin aqueous solution. The enhancement may be attributed to the inclusion interaction between HP‐β‐CD and doxorubicin. The characterization of FTIR, DSC, XRD and fluorescence titration indicates that 1:1 inclusion complex is formed between HP‐β‐CD and doxorubicin.     

Preparation of Imprinted PVB/β‐CD Nanofiber by Electrospinning Technique and Its Selective Binding Abilities for Naringin

A novel molecularly imprinted composite nanofiber was prepared by a simple electrospinning technique, in which polyvinylbutyral (PVB) was chosen as matrix, β‐cyclodextrin (β‐CD) was used as a functional monomer and naringin (NG) as template molecules. After cross‐linked by hexamethylene diisocyanate (HMDI), the composite nanofiber exhibited a high specific binding capacity. The morphological structure of the nanofibers was studied by means of infrared spectrum (IR), X‐ray diffraction (XRD), and scanning electron microscopy (SEM). The β‐CD molecules were mostly homogeneously distributed within the PVB nanofiber without forming phase separated crystalline aggregates. Compared with traditional imprinted β‐CD polymer, the binding experiments demonstrated that the molecularly imprinted composite nanofiber shows the specific binding sites and the selective binding ability for NG. The molecularly imprinted nanofiber could be used at least six times without any loss in binding capacity.     

Electrospun poly(ethylene oxide)/chitosan nanofibers with cellulose nanocrystals as support for cell culture of 3T3 fibroblasts

Chitosan/poly(ethylene oxide) (PEO) (5:1) nanofibers with cellulose nanocrystals (CNCs) were produced using an electrospinning technique. The addition of CNCs to the chitosan/PEO solutions allowed the production of uniform fibers (without beads) with a high proportion of chitosan. The fiber diameters were influenced by the concentration of CNCs in the chitosan/PEO solutions. The solutions containing 10% (w/w) of CNCs produced thinner fibers compared to solutions containing 5% (w/w) of CNCs. Thermogravimetric analysis indicated that the nanofibers were thermally stable, despite the CNCs having an effect on the PEO decomposition. Results from the cell assay in cultures of 3T3 fibroblasts indicated that the chitosan/PEO nanofibers (with 10% CNCs) promoted cell attachment with changes in the cytoskeletal organization. The results obtained in this work highlight the favorable effect of CNCs in electrospinning of chitosan/PEO. As expected, the influence of nanofibers on 3T3 fibroblasts F-actin and β-tubulin network revealed alterations in cytoskeleton, leading to changes in cell morphology and spreading.     

Correlation of polymer-like solution behaviors with electrospun fiber formation of hydroxypropyl-β-cyclodextrin and the adsorption study on the fiber

In this paper, the formation of hydroxypropyl-β-cyclodextrin (HPCD) nanofibers in electrospinning and the adsorption of organic molecules on the HPCD nanofiber were studied. The properties of a polymer-like solution from the highly concentrated HPCD/N,N-dimethylformamide (DMF) solution revealed HPCD supramolecular aggregates formation. The entanglements of HPCD self-organized aggregates were one of the most important factors that significantly influenced fiber formation during cyclodextrin electrospinning. The HPCD self-organized aggregates entanglement concentration (C(e)) was investigated. Analyzing the dependence of specific viscosity (η(sp)) on concentration enabled the determination of the aggregates unentangled and entangled regimes for HPCD polymer-like solutions. The dynamic light scattering (DLS) measurements and the (1)H NMR spectra of the HPCD solutions confirmed the presence of considerable HPCD self-organized aggregates in high concentrated HPCD/DMF solutions due to the intermolecular hydrogen bonding. The scanning electron microscopy (SEM) showed the electrospinning morphology transitioned from regular beads to uniform fibers with increasing the HPCD concentration. The dependence of the fiber diameter on the zero shear rate viscosity (η(0)) was determined. The static adsorption behavior of the HPCD fibers was studied. Neutral red (NR) was used as a model organic molecule. The adsorption of NR onto HPCD fibers fitted the pseudo-second-order kinetic model. The equilibrium adsorption amount of NR was 18.41 mg g(-1), and the apparent adsorption rate constant was 9.83 × 10(-4) g mg(-1) min(-1) at 25 °C.     

NMR and molecular fluorescence spectroscopic study of the structure and thermodynamic parameters of EGCG/β-cyclodextrin inclusion complexes with potential antioxidant activity

The present study is focused on the characterization of the interaction between (?)-epigallocatechingallate (EGCG) and cyclodextrins like β-cyclodextrin (βCD), heptakis(2,6 di-O-methyl)-β-cyclodextrin (DMβCD), and hydroxypropyl-β-cyclodextrin (HPβCD) in aqueous solution. These inclusion complexes previously demonstrated improvements in the antioxidant activity respect to free EGCG. The structural evidence obtained by 2D-ROESY and selective 1D-ROESY experiments was rationalized by autodock studies and indicates that all the complexes have similar inclusion geometries, but the difference resides on the exposition degree of the antioxidant rings of EGCG, such as pyrogallol and galloyl groups. The thermodynamic study allowed estimating that the inclusion process is entalpically driven for the derivatized cyclodextrins complexes and entropically driven for βCD complexes due to the predominance of hydrophobic interactions with EGCG.     

Cyclodextrin short-nanofibers using sacrificial electrospun polymeric matrix for VOC removal

Cyclodextrins (CD) are cyclic oligosaccharides that can form noncovalent host–guest inclusion complexes to yield intriguing supramolecular structures. Electrospinning of nanofibers from CD is challenging since they are small molecules, nonetheless, electrospun nanofibers from CD would be particularly attractive because of the distinctive properties obtained by combining the very large surface area of nanofibers along with the inclusion complexation capability of CD. Herein, we performed the electrospinning of native CD type (i.e. γ-CD) using a minimal amount of carrier polymeric matrix (polyethylene oxide (PEO)). Once, the uniform nanofibers were electrospun from γ-CD/PEO systems, the polymeric carrier matrix was selectively removed by simple washing procedure, at the end, γ-CD short-nanofibers were obtained. We observed that γ-CD short-nanofibers could remove volatile organic compounds (VOC) (i.e. aniline) due to the inclusion complexation capability whereas pristine γ-CD powder could not have the capability for the VOC removal.     

Genipin-modified silk-fibroin nanometric nets

Nanometric silk-fibroin nets were fabricated by electrospinning from regenerated Bombyx mori silk-fibroin (SF)/formic acid solutions with the addition of genipin (GE), 2, 15 and 24 h after the solution preparation. After spinning, the pure fibroin nanofibers were water soluble and needed a further stabilization process, whereas the reaction of fibroin with genipin resulted in water-insoluble fibroin nets due to conformational changes induced in the fibroin by the genipin. SFGE nanofibers presented diameters ranging from 140 to 590 nm and were generally thinner than pure SF nanofibers. The secondary structure of SF into SFGE nanofibers showed the presence of a beta-sheet conformation together with beta-turn intermediates (turns and bends). The approach described in this paper provides an alternative method of designing SF nanofibers that are already water insoluble, without any stability post-treatment needed.     

Double‐layered composite nanofibers and their mechanical performance

Continuous polymer nanofibers are available through electrospinning, but most have the same structure in their cross section. This article focuses on the fabrication and the structural and mechanical characterization of pencil‐like double‐layered composite nanofibers coaxially electrospun from solutions of two different biodegradable materials, i.e., gelatin and poly(ε‐caprolactone) (PCL). Transmission electron microscopy and water contact angle measurements confirmed that a gelatin inner fiber was wrapped with a PCL outer layer. Possible applications of such nanofibers include a controlled degradation rate when used as a medical device in human body. It has been found that the tensile performance of the composite nanofibers was better than those of both the pure constituent, i.e. gelatin and PCL, nanofibers alone. The ultimate strength and ultimate strain of the composite nanofibers with 7.5% w/v gelatin in the core and 10% w/v PCL as shell were at least 68% and 244% higher, respectively, than those of the same concentration pure gelatin and PCL nanofibers. Thus, a coaxial electrospinning technique as used in this article can be applicable, not only in developing functionalized nanofibers but also in elevating their mechanical property. © 2005 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 43: 2852–2861, 2005     

Cyclodextrin solubilization of celecoxib: solid and solution state characterization

The low aqueous solubility of celecoxib (CCB) hampers its oral bioavailability and permeation from aqueous environment through biological membranes. The aim of this study was to enhance the aqueous solubility of CCB by complexation with cyclodextrin (CD) in the presence of water-soluble polymer. The effects of different CDs (αCD, βCD, γCD, 2-hydroxypropyl-β-cyclodextrin and randomly methylated β-cyclodextrin (RMβCD)) and mucoadhesive, water-soluble polymers (hydroxypropyl methylcellulose (HPMC), chitosan and hyaluronic acid) were investigated. The phase solubility profiles and CCB/CD complex characteristics were determined. RMβCD exhibited the greatest solubilizing effect of the two CDs tested. However, γCD was also selected for further investigations due to its safety profile. Addition of polymer to the aqueous CD solutions enhanced the CD solubilization. Formation of CCB/RMβCD/HPMC and CCB/γCD/HPMC ternary complexes resulted in 11 and 19-fold enhancement in the apparent complexation efficiency in comparison to their CCB/CD binary complex, respectively. The size of ternary complex aggregates in solution were determined to be from about 250 to about 350 nm. The data obtained from Fourier transform infra-red, differential scanning calorimetry and powder X-ray diffraction indicated presence of CCB/CD inclusion complexes in the solid state. Proton nuclear magnetic resonance data demonstrated that CCB was partially and totally inserted into the hydrophobic central cavities of RMβCD and γCD.