The aim of this study was to develop a novel controlled ionic gelation strategy for chitosan nanoparticle preparation to avoid particle aggregation tendency associated with conventional ionic gelation process. In this study inclusion complexation behaviour of sodium tripolyphosphate (TPP) with beta cyclodextrin (β-CD) has been investigated. The TPP-β-CD inclusion complex was characterized by FT-IR, XRD and DSC techniques. The complexation behaviour was also investigated by molecular docking study. The results showed that the TPP molecule formed inclusion complex with β-CD. Further, TPP-β-CD inclusion complex was used to prepare chitosan nanoparticles. The chitosan nanoparticles based on TPP-β-CD inclusion complex had smaller size of 104.2nm±0.608, good PDI value of 0.346±0.016 and acceptable zeta potential of +27.33mV±0.416. The surface characteristics of chitosan nanoparticles were also observed with transmission electron microscopy. Results indicates that TPP-β-CD inclusion complex can be used for the formation of chitosan nanoparticles with smaller and more uniform particle size in comparison to conventional TPP based chitosan nanoparticles.
The removal of four parabens, methyl-, ethyl-, propyl-, and benzyl-paraben, by β-cyclodextrin (β-CD) polymer from aqueous solution was studied. Different β-CD polymers were prepared by using two cross-linkers, i.e., hexamethylene diisocyanate (HMDI) and toluene-2,6-diisocyanate (TDI), with various molar ratios of cross-linker. β-CD-HMDI polymer with molar ratio of 1:7 and β-CD-TDI polymer with ratio 1:4 gave the highest adsorption of parabens among the β-CD-HMDI and β-CD-TDI series, and were subsequently used for further studies. The adsorption capacity of β-CD-HMDI is 0.0305, 0.0376, 0.1854 and 0.3026 mmol/g for methyl-, ethyl-, propyl-, and benzyl-paraben, respectively. β-CD-TDI have higher adsorption capacities compared with β-CD-HMDI, the adsorption capacity are 0.1019, 0.1286, 0.2551, and 0.3699 mmol/g methyl-, ethyl-, propyl-, and benzyl-paraben respectively. The parameters studied were adsorption capacity, water retention, and reusability. Role of both cross-linker in adsorption, hydrophobicity of polymers, and adsorption capacity of different parabens were compared and discussed. All experiments were conducted in batch adsorption technique. These polymers were applied to real samples and showed positive results.
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.
The effect of hydroxypropyl methylcellulose (HPMC) concentration on β-cyclodextrin (β-CD) solubilization of norfloxacin was examined. The solubility and dissolution of norfloxacin/β-CD and norfloxacin/β-CD/HPMC inclusion complexes were studied. The presence of β-CD increased significantly the solubility and dissolution of norfloxacin. The addition of HPMC until 5% (w/w) improved the solubilization of norfloxacin but further addition above 5% (w/w), decreased norfloxacin solubilization. Fourier transformed Infra-red (FTIR) showed that norfloxacin was successfully included into β-CD. Differential scanning calorimetry (DSC) showed that the norfloxacin endothermic peak shifted to a lower temperature with reduced intensity indicating the formation of inclusion complex. The addition of HPMC reduced further the intensity of norfloxacin endothermic peak. Most of the sharp and intense peaks of norfloxacin disappeared with the addition of HPMC. In conclusion, the concentration of hydrophilic polymer used to enhance β-CD solubilization of poorly soluble drugs is very critical.
Cyclodextrin-modified micellar electrokinetic chromatography (CD-MEKC) method was developed for simultaneous enantioseparation of three imidazole drugs namely tioconazole, isoconazole and fenticonazole. Three easily available and inexpensive cyclodextrins namely 2-hydroxypropyl-β-cyclodextrin (HP-β-CD), 2-hydroxypropyl-γ-cyclodextrin (HP-γ-CD) and heptakis(2,6-di-O-methyl)-β-cyclodextrin (DM-β-CD) were evaluated to discriminate the six stereoisomers of the drugs. However, none of the three CDs gave a complete enantioseparation of the drugs. Effective enantioseparation of tioconazole, isoconazole and fenticonazole was achieved using a combination of 35 mM HP-γ-CD and 10 mM DM-β-CD as chiral selectors. The best separation using both HP-γ-CD and DM-β-CD (35 mM:10 mM) as chiral selectors were accomplished in background electrolyte (BGE) containing 35 mM phosphate buffer (pH 7.0), 50 mM sodium dodecyl sulfate (SDS) and 15% (v/v) acetonitrile at 27 kV and 30 °C with all peaks resolved in less than 15 min with resolutions, Rs 1.90-27.22 and peak efficiencies, N > 180 000. The developed method was linear over the concentration range of 25-200 mg l(-1) (r(2) > 0.998) and the detection limits (S/N = 3) of the three imidazole drugs were found to be 2.7-7.7 mg l(-1). The CD-MEKC method was successfully applied to the determination of the three imidazole drugs in spiked human urine sample and commercial cream formulation of tioconazole and isoconazole with good recovery (93.6-106.2%) and good RSDs ranging from 2.30-6.8%.
Binding constants for the enantiomers of modafinil with the negatively charged chiral selector sulfated-β-CD (S-β-CD) using CE technique is presented. The calculations of the binding constants employing three different linearization plots (double reciprocal, X-reciprocal and Y-reciprocal) were performed from the electrophoretic mobility values of modafinil enantiomers at different concentrations of S-β-CD in the BGE. The highest inclusion affinity of the modafinil enantiomers were observed for the S-enantiomer-S-β-CD complex, in agreement with the computational calculations performed previously. Binding constants for each enantiomer-S-β-CD complex at different temperatures, as well as thermodynamic parameters for binding, were calculated. Host-guest binding constants using the double reciprocal fit showed better linearity (r(2)>0.99) at all temperatures studied (15-30°C) and compared with the other two fit methods. The linear van't Hoff (15-30°C) plot obtained indicated that the thermodynamic parameters of complexation were temperature dependent for the enantiomers.
Drug targeting is a progressive area of research with folate receptor alpha (FRα) receiving significant attention as a biological marker in cancer drug delivery. The binding affinity of folic acid (FA) to the FRα active site provides a basis for recognition of FRα. In this study, FA was conjugated to beta-cyclodextrin (βCD) and subjected to in silico analysis (molecular docking and molecular dynamics (MD) simulation (100 ns)) to investigate the affinity and stability for the conjugated system compared to unconjugated and apo systems (ligand free). Docking studies revealed that the conjugated FA bound into the active site of FRα with a docking score (free binding energy < -15 kcal/mol), with a similar binding pose to that of unconjugated FA. Subsequent analyses from molecular dynamics (MD) simulations, root mean square deviation (RMSD), root mean square fluctuation (RMSF), and radius of gyration (Rg) demonstrated that FA and FA-βCDs created more dynamically stable systems with FRα than the apo-FRα system. All systems reached equilibrium with stable RMSD values ranging from 1.9-2.4 Å and the average residual fluctuation values of the FRα backbone atoms for all residues (except for terminal residues ARG8, THR9, THR214, and LEU215) were less than 2.1 Å with a consistent Rg value of around 16.8 Å throughout the MD simulation time (0-100 ns). The conjugation with βCD improved the stability and decreased the mobility of all the residues (except residues 149-151) compared to FA-FRα and apo-FRα systems. Further analysis of H-bonds, binding free energy (MM-PBSA), and per residue decomposition energy revealed that besides APS81, residues HIS20, TRP102, HIS135, TRP138, TRP140, and TRP171 were shown to have more favourable energy contributions in the holo systems than in the apo-FRα system, and these residues might have a direct role in increasing the stability of holo systems.
The low bioavailability of polyphenolic compounds due to poor solubility and stability is a major challenge. Encapsulation of polyphenols in zein-based composite nanoparticles can improve the water dispersion, stability, targeted delivery, and controlled release of polyphenols in the gastrointestinal tract. In this study, we investigated the fluorescence properties, bioactivity, and microstructural characteristics of polyphenols during digestion, revealing that zein nanoparticles protect polyphenols from gastric degradation and promote their sustained release in the small intestine. The effects of different ionic species and salt ion concentrations on the digestive properties of polyphenol complex delivery systems have also been explored. In addition, the formation of "protein corona" structures during digestion may affect bioavailability. These findings highlight the potential of nanoparticle formulations to improve polyphenol stability and absorption. The results of this study may provide new insights and references for the study of polyphenol bioavailability enhancement.
The molecularly imprinted polymer (MIP) based on methacrylic acid functionalized β-cyclodextrin (MAA-β-CD) monomer was synthesized for the purpose of selective recognition of benzylparaben (BzP). The MAA-β-CD monomer was produced by bridging a methacrylic acid (MAA) and β-cyclodextrin (β-CD) using toluene-2,4-diisocyanate (TDI) by reacting the -OH group of MAA and one of the primary -OH groups of β-CD. This monomer comprised of triple interactions that included an inclusion complex, π-π interaction, and hydrogen bonding. To demonstrate β-CD performance in MIPs, two MIPs were prepared; molecularly imprinted polymer-methacrylic acid functionalized β-cyclodextrin, MIP(MAA-β-CD), and molecularly imprinted polymer-methacrylic acid, MIP(MAA); both prepared by a reversible addition fragmentation chain transfer polymerization (RAFT) in the bulk polymerization process. Both MIPs were characterized using the Fourier Transform Infrared Spectroscopy (FTIR), Field Emission Scanning Electron Microscopy (FESEM), and Brunauer-Emmett-Teller (BET). The presence of β-CD not only influenced the morphological structure, it also affected the specific surface area, average pore diameter, and total pore volume of the MIP. The rebinding of the imprinting effect was evaluated in binding experiments, which proved that the β-CD contributed significantly to the enhancement of the recognition affinity and selective adsorption of the MIP.
This work aimed to develop a chiral separation method of ketoconazole enantiomers using electrokinetic chromatography. The separation was achieved using heptakis (2, 3, 6-tri-O-methyl)-β-cyclodextrin (TMβCD), a commonly used chiral selector (CS), as it is relatively inexpensive and has a low UV absorbance in addition to an anionic surfactant, sodium dodecyl sulfate (SDS). The influence of TMβCD concentration, phosphate buffer concentration, SDS concentration, buffer pH, and applied voltage were investigated. The optimum conditions for chiral separation of ketoconazole was achieved using 10 mM phosphate buffer at pH 2.5 containing 20 mM TMβCD, 5 mM SDS, and 1.0% (v/v) methanol with an applied voltage of 25 kV at 25 °C with a 5-s injection time (hydrodynamic injection). The four ketoconazole stereoisomers were successfully resolved for the first time within 17 min (total analysis time was 28 min including capillary conditioning). The migration time precision of this method was examined to give repeatability and reproducibility with RSDs ≤5.80% (n =3) and RSDs ≤8.88% (n =9), respectively.
Cyclodextrin-ionic liquid polymer (βCD-BIMOTs-TDI) is a new class of macroporous material and has great potential to be used as an SPE adsorbent material for extraction of phenols in river water samples. Six phenols, as model analytes, were extracted on a βCD-BIMOTs-TDI SPE cartridge, and then, eluted with 2 mL of methanol containing 1% acetic acid. The optimum experimental condition was 15 mL of sample volume (sample at pH 6) and 2 mL of methanol containing 1% acetic acid as an eluent solvent. The eluent concentration was determined by using Gas Chromatography-Flame Ionization Detector (GC-FID). Under optimized condition, high sensitivity (detection limits 0.23-0.35 µg/L) and good recoveries (87-116%) were achieved with satisfactory relative standard deviation (RSD) (0.1-1.7%). The developed βCD-BIMOTs-TDI-SPE was then compared with other adsorbents, and the obtained results showed that the βCD-BIMOTs-TDI exhibited higher extraction recovery due to the unique structure and properties. Finally, the βCD-BIMOTs-TDI was applied as a solid phase extraction sorbent for phenols determination under optimized condition, in river and tap waters, prior to the GC-FID separation.
This work describes methacrylic acid functionalized β-cyclodextrin (MAA-βCD) as a novel functional monomer in the preparation of molecular imprinted polymer (MIP MAA-βCD) for the selective removal of 2,4-dichlorophenol (2,4-DCP). The polymer was characterized using Fourier Transform Infrared (FTIR) spectroscopy, Brunauer-Emmett-Teller (BET) and Field Emission Scanning Electron Microscopy (FESEM) techniques. The influence of parameters such as solution pH, contact time, temperature and initial concentrations towards removal of 2,4-DCP using MIP MAA-βCD have been evaluated. The imprinted material shows fast kinetics and the optimum pH for removal of 2,4-DCP is pH 7. Compared with the corresponding non-imprinted polymer (NIP MAA-βCD), the MIP MAA-βCD exhibited higher adsorption capacity and outstanding selectivity towards 2,4-DCP. Freundlich isotherm best fitted the adsorption equilibrium data of MIP MAA-βCD and the kinetics followed a pseudo-second-order model. The calculated thermodynamic parameters showed that adsorption of 2,4-DCP was spontaneous and exothermic under the examined conditions.
A cloud point extraction (CPE) process using non-ionic surfactant (DC193C) to extract selected paraben compounds from water samples was investigated using reversed phase high performance liquid chromatography (RP-HPLC). The CPE process with the presence of β-cyclodextrin (βCD) functionalized ionic liquid as a modifier (CPE-DC193C-βCD-IL) is a new extraction technique that has been applied on the optimization of parameters, i.e., pH, βCD-IL concentration and phase volume ratio. This CPE-DC193C-βCD-IL method is facilitated at 30 °C, showing great losses of water content in the surfactant-rich phase, resulting in a high pre-concentration factor and high distribution coefficient. The developed method CPE-DC193C-βCD-IL did show enhanced properties compared to the CPE method without the modifier (CPE-DC193C). The developed method of CPE-DC193C-βCD-IL gives an excellent performance on the detection of parabens from water samples with the limit of detection falling in the range of 0.013-0.038 µg mL-1. Finally, the inclusion complex formation, hydrogen bonding, and π-π interaction between the βCD-IL, benzyl paraben (ArP), and DC 193C were proven using 1H NMR and 2D NOESY spectroscopy.
This study aimed to work out a simple and high-yield procedure for the immobilization of horseradish peroxidase on silver nanoparticle. Ultraviolet-visible (UV-vis) and Fourier-transform infrared spectroscopy and transmission electron microscopy were used to characterize silver nanoparticles. Horseradish peroxidase was immobilized on β-cyclodextrin-capped silver nanoparticles via glutaraldehyde cross-linking. Single-cell gel electrophoresis (Comet assay) was also performed to confirm the genotoxicity of silver nanoparticles. To decrease toxicity, silver nanoparticles were capped with β-cyclodextrin. A comparative stability study of soluble and immobilized enzyme preparations was investigated against pH, temperature, and chaotropic agent, urea. The results showed that the cross-linked peroxidase was significantly more stable as compared to the soluble counterpart. The immobilized enzyme exhibited stable enzyme activities after repeated uses.
This study has investigated complexation of fisetin, a natural flavonoid, with three types of cyclodextrins to improve its solubility. Sulfobutylether-β-cyclodextrin (SBE-β-CD) showed the highest complexation efficiency while maintaining the in vitro antioxidant activity of fisetin. Addition of 20%v/v ethanol in water improved the amount of solubilized fisetin in the complex 5.9-fold compared to the system containing water alone. Spray drying of fisetin-SBE-β-CD complex solution in the presence of ethanol produced a dry powder with improved aerosolization properties when delivered from a dry powder inhaler, indicated by a 2-fold increase in the fine particle fraction (FPF) compared to the powder produced from the complex solution containing water alone. The pitted morphological surface of these particles suggested a more hollow internal structure, indicating a lighter and less dense powder. Incorporation of 20%w/w leucine improved the particle size distribution of the powder and further increased the FPF by 2.3-fold. This formulation also showed an EC50 value equivalent to fisetin alone in the A549 cell line. In conclusion, an inhalable dry powder containing fisetin-SBE-β-CD complex was successfully engineered with an improved aqueous solubility of fisetin. The dry powder may be useful to deliver high amounts of fisetin to the deep lung region for therapeutic purposes.
Kenaf seed oil-in-water nanoemulsions (NANO) stabilized by sodium caseinate (SC), beta-cyclodextrin (β-CD), and Tween 20 (T20) have been optimized and shown to improve in vitro bioaccessibility and physicochemical stability in the previous study. The main objective of this study was to evaluate the stability of bioactive compounds and antioxidants in the NANO during storage at different temperatures (4 °C, 25 °C, and 40 °C). An evaluation of the antioxidant activities of each emulsifier showed that SC had good scavenging capability with 97.6% ABTS radical scavenging activity. Therefore, SC which was used as one of the main emulsifiers could further enhanced the antioxidant activity of NANO. At week 8 of storage, NANO that stored at 4 °C had maintained the best bioactive compounds stability and antioxidant activities with 90% retention of vitamin E and 65% retention of phytosterols. These results suggested that 4 °C would be the most suitable storage temperature for NANO containing naturally present vitamin E and phytosterols. From the accelerated storage results at 40 °C, NANO containing vitamin E and phytosterols had maintained half of its initial concentration until week 4 and week 2 of storage, which is equivalent to 16 weeks and 8 weeks of storage at room temperature, respectively.
PRACTICAL APPLICATION: The results of this study provide a better understanding on the stability of bioactive compounds and antioxidant activities in oil-in-water nanoemulsions that stabilized by similar ternary emulsifiers during storage at different temperatures. In addition, this study could be used as a predictive model to estimate the shelf life of bioactive compounds encapsulated in the form of nanoemulsions.
Poly(β-cyclodextrin-ionic liquid) grafted magnetic nanoparticles combined with 1-octanol as supramolecular solvents (SUPRASs) presenting new ferrofluid was developed and successfully applied in the dispersive liquid-phase microextraction of seven representative polycyclic aromatic hydrocarbons. One variable at-a-time (OVAT) analysis and response surface methodology (RSM) were used for efficient optimization of the main variables. The calibration curves were found to be linear in the range of 0.1-150 ng mL-1 with correlation of determinations (R2) ranging from 0.9944 to 0.9986. Detection limits ranged at 0.02-0.07 ng mL-1 for all studied PAHs. The intra and inter-day precision values (RSD %) were in the range of 1.80%-7.56% and 2.97%-8.23%, respectively. The ferrofluid showed a satisfactory reproducibility between 1.72% and 5.90%, and acceptable recovery values at 84%-110% were obtained for the real samples analysis. The optimized method was successfully applied to access the content safety of the PAHs studied in a variety of commercial food and beverages available in Malaysia.
Sorbents were prepared by cross-linking β-cyclodextrin (β-CD) using two different types of cross-linker units at variable reactant mole ratios. The resulting polymers containing β-CD were evaluated as sorbents in micro-solid phase extraction (μ-SPE) format for the extraction of the endogenous steroids testosterone (T), epitestosterone (E), androsterone (A), etiocholanolone (Etio), 5α-androstane-3α,17β-diol (5αAdiol) and 5β-androstane-3α,17β-diol (5βAdiol). The best sorbent (C1; cyclodextrin polymer) showed superior extraction characteristics compared with commercial sorbents (C18 and Bond Elut Plexa). Parameters influencing the extraction efficiency of the C1 sorbent such as extraction and desorption times, desorption solvent and volume of sample were investigated. The extracts were separated using a Hypersil Gold column (50 × 2.1 mm, 1.9 μm) under gradient elution coupled to a LC-MS/MS. The compounds were successfully separated within 8 min. The method offers good repeatability (RSD 0.995) were within the range of 1-200 ng mL-1 for T and E, 250-4000 ng mL-1 for A and Etio and 25-500 ng mL-1 for 5αAdiol and 5βAdiol, respectively. The method was applied for the determination of steroid profile of urine from volunteers.
β-Cyclodextrin-ionic liquid polymer (CD-ILP) was first synthesized by functionalized β-cyclodextrin (CD) with 1-benzylimidazole (BIM) to form monofunctionalized CD (βCD-BIMOTs) and was further polymerized using a toluene diisocyanate (TDI) linker to form insoluble CD-ILP (βCD-BIMOTs-TDI). The βCD-BIMOTs-TDI polymer was characterized using various tools and the results obtained were compared with those derived from the native β-cyclodextrin polymer (βCD-TDI). The SEM result shows that the presence of ionic liquid (IL) increases the pore size, while the thermo gravimetric analysis (TGA) result shows that the presence of IL increases the stability of the polymer. Meanwhile, Brunauer-Emmett-Teller (BET) results show that βCD-BIMOTs-TDI polymer has 1.254 m(2)/g surface areas and the Barret-Joyner-Halenda (BJH) pore size distribution result reveals that the polymer exhibits macropores with a pore size of 77.66 nm. Preliminary sorption experiments were carried out and the βCD-BIMOTs-TDI polymer shows enhanced sorption capacity and high removal towards phenols and As(V).
The increase in diseases of the colon underscores the need to develop cost-effective site-directed therapies. We formulated a polysaccharide-based matrix system that could release ibuprofen under conditions simulating those in the colon by employing a wet granulation method. Tablets were prepared in a series of formulations containing a polysaccharide (beta-cyclodextrin and chitosan) matrix system along with ethylcellulose. We characterized physicochemical properties and performed an in vitro drug release assay in the absence and presence of digestive enzymes to assess the ability of the polysaccharides to function as a protective barrier against the upper gastrointestinal environment. Fourier transform infrared spectroscopy studies revealed no chemical interaction between ibuprofen and polysaccharides; however, spectrum analysis suggested the formation of an inclusion complex of beta-cyclodextrin with ibuprofen. The formulations contained 50% ethylcellulose and 50% beta-cyclodextrins (1:1) were proven to be the better formulation that slowly released the drug until 24 h (101.04 ± 0.65% maximum drug release in which 83.08 ± 0.89% drug was released in colonic medium) showed better drug release profiles than the formulations containing chitosan. We conclude that a beta-cyclodextrin drug carrier system may represent an effective approach for treatment of diseases of the colon.