Β-cyclodextrin Hydrogels Research Articles

Edible thermosensitive chitosan/hydroxypropyl β-cyclodextrin hydrogel with natural licoricidin for enhancing oral health: Biofilm disruption and demineralization prevention

Dental caries, a widespread and significantly detrimental health condition, is characterized by demineralization, pain, compromised tooth functionality, and various other adverse effects. Licoricidin (LC), a natural isoflavonoid, demonstrates potent antimicrobial properties for maintaining oral health. However, its practical application is significantly hindered by its limited water solubility and susceptibility to removal within the oral environment. To tackle this issue, we developed a delivery oral system by an edible thermosensitive chitosan- disodium beta-glycerol phosphate pentahydrate (CS/β-GP) hydrogel to load LC/Hydroxypropyl beta-cyclodextrin (HP-β-CD) inclusion complexes. These hydrogels (LC/HP-β-CD/CS/β-GP) could solidify rapidly at oral temperature and sustainably release LC, thereby preventing its rapid clearance from the oral cavity. We confirmed the significant antibacterial activity of this hydrogel against Streptococcus mutans and Staphylococcus aureus. Additionally, the HP-β-CD combination enhanced LC to penetrate bacterial biofilms and inhibit biofilm growth, leading to leakage of cellular proteins and DNA. Additionally, we studied the effect of LC/HP-β-CD/CS/β-GP on intracellular ROS levels and MMP, comprehensively exploring its antimicrobial mechanism. Furthermore, LC/HP-β-CD/CS/β-GP exhibited the ability to inhibit demineralization and demonstrated excellent biocompatibility. In summary, this study presented a safer approach to oral delivering bioactive substances, offering a promising strategy for enhanced oral health and safety.

Immobilization of Laccase in β-Cyclodextrin Composite Hydrogel for Efficient Degradation of Dye Pollutants

A stable and efficient biocatalyst was prepared by encapsulating Trametes versicolor laccase using an acrylic acid-grafted β-cyclodextrin hydrogel (Lac-CD-PAA). Scanning electron microscopy and nitrogen adsorption-desorption experiments showed that there were regularly distributed channels in the spongy Lac-CD-PAA. In addition, a large number of mesopores and macropores existed in the wall of the hydrogel lamellae. This network structure reduced the diffusion resistance of the hydrogel to the target substrate. The relative activity of the resulting Lac-CD-PAA could be maintained at 35.8% after six cycles of use. Lac-CD-PAA exhibited higher thermal and chemical stability compared to free laccase. The negative charge on the surface of Lac-CD-PAA gives it the ability to pretreat cationic dyes. In six consecutive methylene blue decolorization tests, Lac-CD-PAA decolorized better than free laccase. The results showed that the prepared β-cyclodextrin-based composite hydrogel was a good carrier for laccase.

Modified β-Cyclodextrin hydrogel for selective adsorption and desorption for cationic dyes

Modified β-Cyclodextrin hydrogel for selective adsorption and desorption for cationic dyes

A novel enzyme-free long-lasting chemiluminescence system based on a luminol functionalized β-cyclodextrin hydrogel for sensitive detection of H2O2 in urine and cells.

A novel long-lasting chemiluminescent (CL) hydrogel (β-CD@luminol-Co2+) was synthesized by embedding luminol and cobalt ions (Co2+) into β-cyclodextrin (β-CD) through non-covalent interactions. Due to its porous structure and viscosity, the synthesized β-CD@luminol-Co2+ hydrogel exhibited long-lasting CL properties and can emit light for 12 h under both alkaline and neutral conditions. In addition, the CL intensities of β-CD@luminol-Co2+ were linear with the logarithm of the hydrogen peroxide (H2O2) concentration in the range of 1.0 × 10-11-1.0 × 10-7 M, and the limit of detection (LOD) was 0.63 × 10-11 M and 0.85 × 10-11 M under alkaline and neutral conditions, respectively. On this basis, an enzyme-free CL sensor based on β-CD@luminol-Co2+ was fabricated for the sensitive detection of H2O2 in human urine samples under alkaline conditions, and showed good accuracy and recovery. Since β-CD@luminol-Co2+ showed good CL properties under neutral conditions, it can be applied to detect H2O2 in cells. In order to prolong the emission wavelength of β-CD@luminol-Co2+ for better cell imaging, β-CD@luminol-FL-Co2+ was prepared by adding fluorescein (FL) to β-CD@luminol-Co2+. The as-prepared β-CD@luminol-FL-Co2+ also displayed long-lasting CL properties and showed a linear relationship with H2O2 concentrations. In addition, the maximum emission wavelength of β-CD@luminol-FL-Co2+ was 520 nm, which was red-shifted by 95 nm compared with β-CD@luminol-Co2+. The methyl thiazolyl tetrazolium (MTT) assay results and confocal microscopy images illustrated that β-CD@luminol-FL-Co2+ had low toxicity and can be taken up by A549 cells. Finally, β-CD@luminol-FL-Co2+ was successfully applied for CL imaging and detection of intracellular H2O2 in A549 cells under neutral conditions. This enzyme-free long-lasting CL system with high sensitivity can also be extended to real-time monitoring of H2O2in vivo.

Natural polymers-enhanced double-network hydrogel as wearable flexible sensor with high mechanical strength and strain sensitivity

Conductive hydrogels have shown great prospects as wearable flexible sensors. Nevertheless, it is still a challenge to construct hydrogel-based sensor with great mechanical strength and high strain sensitivity. Herein, an ion-conducting hydrogel was fabricated by introducing gelatin-dialdehyde β-cyclodextrin (Gel-DACD) into polyvinyl alcohol-borax (PVA-borax) hydrogel network. Natural Gel-DACD network acted as mechanical deformation force through non-covalent cross-linking to endow the polyvinyl alcohol-borax/gelatin-dialdehyde β-cyclodextrin hydrogel (PGBCDH) with excellent mechanical stress (1.35 MPa), stretchability (400%), toughness (1.84 MJ/m3) and great fatigue resistance (200% strain for 100 cycles). Surprisingly, PGBCDH displayed good conductivity of 0.31 S/m after adding DACD to hydrogel network. As sensor, it showed rapid response (168 ms), high strain sensitivity (gage factor (GF) = 8.57 in the strain range of 200%-250%) and reliable sensing stability (100% strain for 200 cycles). Importantly, PGBCDH-based sensor can accurately monitor complex body movements (knee, elbow, wrist and finger joints) and large-scale subtle movements (speech, swallow, breath and facial expressions). Thus, PGBCDH shows great potential for human monitoring with high precision.

Poly(N-vinyl imidazole) Cross-Linked β-Cyclodextrin Hydrogel for Rapid Hemostasis in Severe Renal Arterial Hemorrhagic Model.

A unique facile process has been adopted for fast assembly of a poly(N-vinyl imidazole) cross-linked β-cyclodextrin hydrogel through microwave-assisted free radical polymerization, using N,N'-methylenebis(acrylamide) cross-linker. The copolymer possesses positive surface charge, one of the characteristic properties of an ideal hemostatic hydrogel. The functionalized imidazole-based hydrogel demonstrates rapid, superior blood coagulation kinetics under in vitro and in vivo conditions. On application to a major renal arterial hemorrhagic model, this hydrogel shows better blood clotting kinetics, leading to complete hemostasis in as few as ∼144 ± 7 s. Additionally, 350 μL of whole blood was clotted instantly, in ∼35 s, and therefore, reinforcing its hemostatic potential. The hydrogel demonstrates excellent biocompatibility, when seeded with human dermal fibroblast cells, retaining the native property of its predecessor. In addition, the hydrogel presents excellent hemocompatibility when tested with whole blood with the highest hemolytic ratio of 1.07 ± 0.05%. Moreover, it also demonstrates potential as a carrier for sustained release of an anesthetic drug, lidocaine hydrochloride monohydrate (∼83% in 24 h). The rapid hemostatic behavior of the hydrogel is coupled with its cytocompatibility and hemocompatibilty properties along with controlled drug release characteristics. These behaviors evidently demonstrate it to be an excellent alternative for a superior hemostatic material for severe hemorrhagic conditions.

Preparation and Properties of Double Sensitive β-Cyclodextrin Hydrogel

In this paper, partly esterified β-cyclodextrin derivative had been synthesized by esterification of β-cyclodextrin and maleic anhydride. Then, it is amidated by diethanolamine. β-Cyclodextrin copolymer had been prepared from amidated β-cyclodextrin derivative, cholic acid and epichlorohydrin in sodium hydroxide aqueous solution. β-Cyclodextrin hydrogel had been prepared through radical polymerization of β-cyclodextrin copolymer, N-isopropylacrylamide and acrylic acid. The structures, compositions and morphology of the hydrogel were characterized by infrared spectroscopy, nuclear magnetic resonance, differential scanning calorimetry and field-emission scanning electron microscope. Its properties were tested and analyzed by ultraviolet spectroscopy, thermogravimetric analysis and swelling experiments. The results show that the β-cyclodextrin hydrogel owns sustained release performance, temperature and pH sensitivities.

Chemically crosslinked xylan–β-Cyclodextrin hydrogel for the in vitro delivery of curcumin and 5-Fluorouracil

Novel hydrogels were synthesized from xylan and β-Cyclodextrin using Ethylene Glycol Diglycidyl Ether as a crosslinker in alkaline medium at different molar ratio. The physical characterization of hydrogels was carried out by the swelling study whereas the chemical characterization was performed in Fourier Transform Infrared Spectroscopy. The morphological analysis revealed the porous structure of hydrogel and the rheological study summarised the flow behavior and gelation characteristics of the hydrogels. Curcumin and 5-Fluorouracil (5-FU) were used as the model drugs to be loaded in hydrogel and subsequent studies involving the in vitro release in phosphate buffer saline (PBS, pH = 7.4). The hydrogels showed drug loading of 98% of 5-FU and 26% of curcumin. Furthermore, the gels showed the highest cumulative release of 56% 5-FU and 37% curcumin after 24 h. The kinetics of drug release was then analyzed by various kinetic models.

Glucose-responsive poly(vinyl alcohol)/β-cyclodextrin hydrogel with glucose oxidase immobilization

Glucose-responsive poly(vinyl alcohol)/β-cyclodextrin (PVA/β-CD) hydrogels cross-linked by citric acid were prepared through an environment-friendly synthesis procedure. The glucose oxidase (GOx) was physically immobilized within the β-CD cavity for accurate detection of interstitial fluid glucose levels reaching approximately 1 mM. We evaluated the viscoelastic behavior of the PVA/β-CD solutions through dynamic oscillatory shear testing, and the PVA/β-CD/GOx hydrogel 10 shows the optimal properties with excellent water absorption (312 ± 17%), low solubility, and long moisture retention time (approximately 4.5 h for complete drying at 37 °C). The PVA/β-CD/GOx hydrogel showed the high flexural and tensile strengths of ≥ 400 and ≥ 5 MPa, respectively. Furthermore, the fabricated PVA/β-CD/GOx hydrogel 10 displayed a linear amperometric response (R2 is 0.984) in the glucose concentration range from 1.0 to 5.0 mM with a relatively high sensitivity of 7.58 µA mM−1 and a low detection limit of 5.141 × 10−4 M at low applied potential (0.27 V vs. Ag/AgCl coated with Prussian blue), indicating its great potential as a patch sensor for noninvasive glucose monitoring.

Synthesis of β-cyclodextrin hydrogel nanoparticles for improving the solubility of dexibuprofen: characterization and toxicity evaluation

Objective: This study was aimed to enhance aqueous solubility of dexibuprofen through designing β-cyclodextrin (βCD) hydrogel nanoparticles and to evaluate toxicological potential through acute toxicity studies in rats.Significance: Dexibuprofen is a non-steroidal analgesic and anti-inflammatory drug that is one of safest over the counter medications. However, its clinical effectiveness is hampered due to poor aqueous solubility.Methods: βCD hydrogel nanoparticles were prepared and characterized by percent yield, drug loading, solubilization efficiency, FTIR, XRD, DSC, FESEM and in-vitro dissolution studies. Acute oral toxicity study was conducted to assess safety of oral administration of prepared βCD hydrogel nanoparticles.Results: βCD hydrogel nanoparticles dramatically enhanced the drug loading and solubilization efficiency of dexibuprofen in aqueous media. FTIR, TGA and DSC studies confirmed the formation of new and a stable nano-polymeric network and interactions of dexibuprofen with these nanoparticles. Resulting nanoparticles were highly porous with 287 nm in size. XRD analysis revealed pronounced reduction in crystalline nature of dexibuprofen within nanoparticles. Release of dexibuprofen in βCD hydrogel nanoparticles was significantly higher compared with dexibuprofen tablet at pH 1.2 and 6.8. In acute toxicity studies, no significant changes in behavioral, physiological, biochemical or histopathologic parameters of animals were observed.Conclusions: The efficient preparation, high solubility, excellent physicochemical characteristics, improved dissolution and non-toxic βCD hydrogel nanoparticles may be a promising approach for oral delivery of lipophilic drugs.

Synthesis and characterization of poly(2-hydroxyethylacrylate)/β-cyclodextrin hydrogels obtained by frontal polymerization

For the first time, the synthesis of polymeric hydrogels containing cyclodextrins (CDs) obtained by frontal polymerization (FP) is reported. In particular, the effects of CDs on poly(2-hydroxyethylacrylate) hydrogel properties are investigated. In a first series of materials, β-cyclodextrin is dispersed into the polymer matrix, while in the second one acryloyl-β-cyclodextrin is grafted to poly(2-hydroxyethylacrylate) chains. FP parameters (front velocity and maximum temperature), swelling properties, glass transition temperatures and mechanical properties of the hydrogels are studied. Results show that both types of cyclodextrin influence the above properties, and the major effects are found for concentration higher than 1mol% of acryloyl-β-cyclodextrin. Namely, a significant increase of glass transition temperature and of compression moduli are found. Finally, this study demonstrates that FP is a convenient technique to obtain CD-containing hydrogels, in which the type and amount of cyclodextrin can be suitably modulated to tune polymer properties, in function of the desired hydrogel applications.

Multifunctional hydrogels based on β-cyclodextrin with both biomineralization and anti-inflammatory properties

In this study, a series of carboxylated hydrogels are synthesized using β-cyclodextrin, epichlorohydrin and succinic anhydride. It is found that the carboxyl groups on the β-cyclodextrin hydrogels could facilitate the biomineralization process in the simulated body fluid. The new generated minerals are apatite and similar to that of bones. Meanwhile, the carboxylated β-cyclodextrin hydrogels can also load and release anti-inflammatory drug (using indomethacin as a model) in a controlled manner during the biomineralization process for 28 days. The carboxylated β-cyclodextrin hydrogels also have low cytotoxicity and are promising for bone tissue engineering.

β-Cyclodextrin hydrogels as potential drug delivery systems

► Insoluble cyclodextrin polymers as discs with a controlled geometry have been synthesized. ► Interaction between the polymers and model drugs in the solid state canbe evidenced. ► Kinetic, diffusion constants and diffusion coefficients have been calculated. ► In vitro drug release studies followed a simple Fickian diffusion mechanism. ► The synthesized matrices are potentially suitable as sustained release systems. β-cyclodextrins (βCD) are cyclic oligosaccharides which have been widely employed for pharmaceutical applications. Discs of insoluble polymers were synthesized by crosslinking β-cyclodextrins with the reagent epichlorohydrin. In this work, the possibility of employing a polymer containing 60 ± 3% βCD for drug delivery of two antiinflammatory (naproxen and nabumetone) and two antifungal drugs (naftifine and terbinafine) has been investigated. The interaction of Naproxen with the polymers was evidenced by X-ray diffractometry, FTIR spectroscopy and differential thermal analysis. Drug release kinetics were carried out at physiological conditions of pH and temperature, and kinetic and diffusion constants were calculated by fitting 60% of the release profile according to the Korsmeyer–Peppas equation. Also, diffusion coefficients were calculated according to the simplified Higuchi model. The drug release followed a simple Fickian diffusion mechanism for all the model drugs. This study suggests that these hydrogel matrices are potentially suitable as sustained release systems.

Experimental Studies and Modeling of Drug Release from a Tunable Affinity-Based Drug Delivery Platform

An affinity-based drug delivery platform for controlling drug release is analyzed by a combination of experimental studies and mathematical modeling. This platform has the ability to form selective interactions between a therapeutic agent and host matrix that yields advantages over systems that employ nonselective methods. The incorporation of molecular interactions in drug delivery can increase the therapeutic lifetime of drug delivery implants and limit the need for multiple implants in treatment of chronic illnesses. To analyze this complex system for rational design of drug delivery implants, we developed a mechanistic mathematical model to quantify the molecular events and processes. With a β-cyclodextrin hydrogel host matrix, defined release rates were obtained using a fluorescent model drug. The key processes were the complexation between the drug and cyclodextrin and diffusion of the drug in the hydrogel. Optimal estimates of the model parameters were obtained by minimizing the difference between model simulation and experimentally measured drug release kinetics. Model simulations could predict the drug release dynamics under a wide range of experimental conditions.

β -Cyclodextrin hydrogel incorporating hydrophobically modified poly(N -isopropylacrylamide) for a temperature-dependent release

Hydrogels exhibiting a temperature-dependent release were prepared by incorporating hydrophobically modified poly(N-isopropylacrylamide) (HmPNIPAM) into β-cyclodextrin hydrogels (β-CD hydrogels). The specific loading of HmPNIPAM was about 0.0069 g HmPNIPAM/g β-CD hydrogels. The incorporation of the polymer was qualitatively conformed by FT-IR spectroscopy and SEM. The percent release of blue dextran in 24 hr at 20°C (about 77%) was markedly higher than those obtained at 35°C and 45°C (about 53 and 55%, respectively). At the higher temperatures, the volume of the hydrogel could decrease upon the thermal contraction of HmPNIPAM, leading to a smaller mesh and a suppressed release. In fact, the swelling ratio in 24 hr at 35°C and 45°C (about 396% and 405%, respectively) was obviously lower than that obtained at 20°C (about 465%). Copyright © 2011 John Wiley & Sons, Ltd.