Β-cyclodextrin Polymer Research Articles

Supramolecular modified porous carbons with hierarchical adsorption of quinone active molecules for high performance supercapacitors

Quinone active molecules (QAM) with high redox activity, large capacitance and exceptional electrochemical reversibility, allow for the creation of eco-sustainable and high-energy density electrode materials. However, its low conductivity and easy solubility limit its application. This study presents a novel strategy to construct QAM/CDP@PC supramolecular nanostructures for supercapacitors by in situ polymerisation of β-cyclodextrin polymers (CDP) onto porous carbon (PC), which as supramolecular acceptors, and enrichment of the guest molecule QAM (alizarin red, sodium anthraquinone-2-sulfonate, 2,6-diaminoanthraquinone). The transformation and binding energy of QAM in electrochemical processes were investigated through the use of in-situ XPS, FTIR, and DFT calculations. The results indicate that the QAM/CDP@PC exhibits better performance than most quinone based supercapacitors in terms of specific capacitance (805 F/g) and capacity retention (95.3 %). This study provides a promising strategy for the development of organic supercapacitors with increased capacity and improved cycling stability.

Constructing Quasi-Single Ion Conductors by a β-Cyclodextrin Polymer to Stabilize Zn Anode.

Aqueous Zn-ion batteries (AZIBs) are promising for the next-generation large-scale energy storage. However, the Zn anode remains facing challenges. Here, we report a cyclodextrin polymer (P-CD) to construct quasi-single ion conductor for coating and protecting Zn anodes. The P-CD coating layer inhibited the corrosion of Zn anode and prevented the side reaction of metal anodes. More important is that the cyclodextrin units enabled the trapping of anions through host-guest interactions and hydrogen bonds, forming a quasi-single ion conductor that elevated the Zn ion transference number (from 0.31 to 0.68), suppressed the formation of space charge regions and hence stabilized the plating/striping of Zn ions. As a result, the Zn//Zn symmetric cells coated with P-CD achieved a 70.6 times improvement in cycle life at high current densities of 10 mA cm-2 with 10 mAh cm-2. Importantly, the Zn//K1.1V3O8 (KVO) full-cells with high mass loading of cathode materials and low N/P ratio of 1.46 reached the capacity retention of 94.5 % after 1000 cycles at 10 A g-1; while the cell without coating failed only after 230 cycles. These results provide novel perspective into the control of solid-electrolyte interfaces for stabilizing Zn anode and offer a practical strategy to improve AZIBs.

Multivalent supramolecular fluorescent probes for accurate disease imaging.

Optical imaging is a powerful tool for early disease detection and effective treatment planning, but its accuracy is often compromised by the uptake of imaging materials by the mononuclear phagocyte system (MPS). Herein, we leverage multivalent host-guest interactions between cyanine dyes and β-cyclodextrin polymers to develop supramolecular probes with enhanced stability, optical, and transport profiles for accurate in vivo imaging. These multivalent interactions not only ensure the stability of the probes but also enhance fluorescence efficiency by minimizing nonradiative decay. Our self-assembly approach effectively modulates probe size and surface properties, enabling evasion of MPS clearance and promoting prolonged bloodstream circulation, thereby improving the signal-to-background ratio for imaging. The effectiveness of our design is demonstrated by substantial advancements in the early diagnosis of acute kidney injury and by providing high-contrast imaging and precise surgical navigation across various tumor models. Our strategy not only advances optical imaging materials toward clinical translation but also establishes a versatile platform applicable to multiple imaging modalities.

Eco-Friendly Voltammetric Analysis of Flibanserin with Electropolymerized β-Cyclodextrin on Carbon Sensors

This study developed a cost-effective method to determine flibanserin (FLN) using a screen-printed carbon electrode modified with β-Cyclodextrin polymer (SPCE/β-CD). The electrode was modified in Britton-Robinson buffer at pH 5.0 to enhance FLN’s electrochemical oxidation, with cyclic and differential pulse voltammetry used for detection. Characterization techniques included energy-dispersive X-ray analysis, scanning electron microscopy, and Fourier transform infrared spectroscopy. The method showed a linear response to FLN concentrations ranging from 5.2 to 80.0 ng ml−1, with a detection limit of 0.004 μM and a quantitation limit of 0.014 μM. The modified electrode demonstrated good sensitivity, reproducibility, and was applied successfully to FLN analysis in spiked human serum and urine samples. An environmental impact assessment was conducted using the Green Analytical Procedure Index, which evaluates the green characteristics of the entire analytical methodology from sample collection to final determination. Additionally, the Analytical Eco-Scale, which assesses the use of organic preparations, procedures, and instruments, demonstrated a favorable green analysis profile. This modified electrode provides a convenient, cost-effective, and eco-friendly approach for determining flibanserin in various matrices.

Pharmacological effects and the related mechanism of scutellarin on inflammation-related diseases: a review.

Inflammation is a biological response of multicellular organisms caused by injuries, pathogens or irritants. An excessive inflammatory response can lead to tissue damage and various chronic diseases. Chronic inflammation is a common feature of many diseases, making the search for drugs to treat inflammation-related diseases urgent. Scutellarin, a natural flavonoid metabolite, is widely used in the treatment of various inflammation-related diseases for its anti-inflammatory, anti-oxidant and anti-cancer activities. Scutellarin can inhibit key inflammatory pathways (PI3K/Akt, MAPK, and NF-κB, etc.) and activate the anti-oxidant related pathways (Nrf2, ARE, ect.), thereby protecting tissues from inflammation and oxidative stress. Modern extraction technologies, such as microwave-assisted, ultrasound assisted, and supercritical fluid extraction, have been utilized to extract scutellarin from Scutellaria and Erigeron genera. These technologies improve efficiency and retain biological activity, making scutellarin suitable for large-scale production. Scutellarin has significant therapeutic effects in treating osteoarthritis, pulmonary fibrosis, kidney injury, and cardiovascular diseases. However, due to its low bioavailability and short half-life, its clinical application is limited. Researchers are exploring innovative formulations (β-cyclodextrin polymers, triglyceride mimetic active ingredients, and liposome precursors, etc.) to improve stability and absorption rates. Despite these challenges, the potential of scutellarin in anti-inflammatory, anti-oxidant, and anti-cancer applications remains enormous. By optimizing formulations, exploring combination therapies, and conducting in-depth mechanistic research, scutellarin can play an important role in treating various inflammatory diseases, providing patients with more and effective treatment options.

Porous β-cyclodextrin polymers for rapid and efficient removal of organic micropollutants from water: The role of sulfonation and porosity on adsorption performance

Removal of organic micropollutants (OMPs) from water, especially hydrophilic and ionized ones, is challenging for water remediation. Herein, porous β-cyclodextrin polymers (PCPs) with tailored functionalization were prepared based on molecular expansion strategy and sulfonation. Partially benzylated β-cyclodextrin was knotted by external crosslinker to form PCP1, and knotting PCP1 by expansion molecule generated PCP2. PCP1 and PCP2 were sulfonated to achieve PCP1–SO3H and PCP2–SO3H. Based on systematical adsorption evaluation toward multiple categories of OMPs, it was found that the introduced strong polar –SO3H group could bring strong hydrogen bonding and electrostatic interactions. PCP2 showed the highest surface (998.97 m2/g) displayed more excellent adsorption performance toward neutral and anionic OMPs, and the adsorption mechanism for this property of PCP2 was dominated by hydrophobic interactions. In addition, the PCP1–SO3H with the lowest surface area (39.75 m2/g) rather than PCP2–SO3H with higher surface (519.28 m2/g) exhibited more superior adsorption towards hydrophilic and cationic OMPs, benefiting by hydrogen bonding and electrostatic interactions as well as appropriate porosity. These results not only confirmed the performance enhancement of PCPs through the integration of novel preparation strategy, but also provided fundamental guidance for PCPs design for water remediation.

An economic, accessible and stable sulphated cyclodextrin polymer as selector for efficiently separating chiral drugs in HPLC

In this study, sulfopropyl ether β-cyclodextrin polymer (SPE-β-CDP) with simple synthesis steps using cheap reagents was large-scalely prepared. Characterization results showed the average sulfonic group substitution in each β-CD molecule was about 7.261, and there were 195.87 μmol/g β-CD units in polymer. It was low viscosity and produced a little effect on column pressure. It was used as chiral selectors first time to add into mobile phase to separate 13 chiral drugs in HPLC. After investigation, results showed buffer pH, chiral additive concentration, organic phase proportion in mobile phase and flow rate could affect chiral separation. High separation ability of SPE-β-CDP was proved through baseline separation of 12 drugs which attributed to the homogeneity of SPE-β-CDP in sulfonic acid group substitution degree and position. The resolutions of salbutamol, bisoprolol, chlorpheniramine, propranolol and metoprolol could be even up to 7.47–19.02, which were significantly better than that of some references. Separations of 4 chiral drugs were even better than that of CE. Compared with monomer, SPE-β-CDP showed better chiral separation ability. SPE-β-CDP could be used in both of C8 and C18 columns. It was stable in batches and showed good recyclability and reusability. These provided a new strategy for chiral separation.

A universal electrochemical sensor for detection of nucleic acids and protein based on host-guest recognition of β-cyclodextrin polymer

A novel electrochemical sensing approach was developed to detect DNA, RNA, and protein targets, utilizing the host–guest interaction between methylene blue (MB)-labeled probe and β-cyclodextrin-based nanocomposite (rGO/β-CDP). During the assay, the MB-labeled probe interacted with the corresponding target to form a probe/target complex. Due to steric hindrance, the formation of this complex reduced the amount of MB-labeled probes that can be captured by the β-cyclodextrin-based nanocomposite on the electrode surface, resulting in a measurable decrease in the electrochemical signal. Upon optimization, the sensing platform exhibited satisfactory analytical performance for three cancer-related model analytes: p53 DNA, microRNA-21 RNA, and thrombin protein, achieving low detection limits of 3.4 nM, 4.4 nM, and 5.7 pM, respectively. In this work, the electrochemical assay separates the detection process into two stages: target recognition in solution and signal transduction on the electrode surface. This fabrication effectively circumvents the issues associated with nonspecific conformational changes and the complicated probe installation procedures on electrode surfaces that are common in traditional sensing platforms. Integrating host–guest recognition with electrochemical assay, the developed approach not only advances the understanding of host–guest chemistry in sensor applications but also establishes a foundation for future innovations in the detection of biomarkers.

Perfluoroalkyl acid adsorption by styrenic β-cyclodextrin polymers, anion-exchange resins, and activated carbon is inhibited by matrix constituents in different ways

Perfluoroalkyl acids (PFAAs) are ubiquitous environmental contaminants of global concern, and adsorption processes are the most widely used technologies to remove PFAAs from water. However, there remains little data on the ways that specific water matrix constituents inhibit the adsorption of PFAAs on different adsorbents. In this study, we evaluated the adsorption of 13 PFAAs on two styrene-functionalized β-cyclodextrin (StyDex) polymers, an activated carbon (AC), and an anion-exchange resin (AER) in the absence and presence of specific water matrix constituents (16 unique water matrices) in batch experiments. All four adsorbents exhibited some extent of adsorption inhibition in the presence of inorganic ions and/or humic acid (HA) added as a surrogate for natural organic matter. Two PFAAs (C5-C6 perfluorocarboxylic acids (PFCAs)) were found to exhibit relatively weak adsorption and five PFAAs (C6-C8 perfluorosulfonic acids (PFSAs) and C9-C10 PFCAs) were found to exhibit relatively strong adsorption on all four adsorbents across all matrices. Adsorption inhibition was the greatest in the presence of Ca2+ (direct site competition) and HA (direct site competition and pore blockage) for AC, NO3- (direct site competition) and Ca2+ (chemical complexation) for the AER, and SO42- (compression of the double layer) for the StyDex polymers. The pattern of adsorption inhibition of both StyDex polymers were similar to each other but different from AC and AER, which demonstrates the distinctive PFAA adsorption mechanism on StyDex polymers. The unique performance of each type of adsorbent confirms unique adsorption mechanisms that result in unique patterns of adsorption inhibition in the presence of matrix constituents. These insights could be used to develop models to predict the performance of these adsorbents in real water matrices and afford rational selection of adsorbents based on water chemistry for specific applications.

Structural Features of Styrene-Functionalized Cyclodextrin Polymers That Promote the Adsorption of Perfluoroalkyl Acids in Water.

Cross-linked β-cyclodextrin (β-CD) polymers are promising adsorbents for the removal of per- and polyfluoroalkyl substances (PFAS) from contaminated water sources, including contaminated groundwater, drinking water, and wastewater. We previously reported porous, styrene-functionalized β-cyclodextrin (StyDex) polymers derived from radical polymerization with vinyl comonomers. Because of the versatility of these polymerizations, StyDex polymer compositions are tunable, which facilitates efforts to establish structure-adsorption relationships and to discover improved materials. Here, we evaluate the material properties and PFAS adsorption of 20 StyDex derivatives with varied comonomer structure and loading, regiochemistry of styrene placement on the CD monomer, and CD size. A StyDex polymer containing N,N'-dimethylbutyl ammonium ions exhibited the most effective PFAS adsorption in batch experiments. Furthermore, a StyDex polymer containing β-CD exhibited size-selective host-guest interactions with perfluoroalkyl acids (PFAAs) and neutral contaminants in aqueous electrolyte when compared to similar polymers containing either α-CD or γ-CD. Polymers based on β-CD monomers with an average of seven styrene groups randomly positioned over the 21 available hydroxyl groups performed similarly to those based on a β-CD monomer functionalized regiospecifically at each of the seven 6' positions. The former β-CD monomer is prepared in a single step from unmodified β-CD, so the ability to use it without compromising performance demonstrates promise for developing economically competitive adsorbents. These results offered important insights into structure-adsorption properties of StyDex polymers and will inform the design of improved StyDex formulations.

Synthesis and characterization of β-cyclodextrin polymers and its performance as a drug carrier

The aim of this study was to determine the optimal reaction conditions for the synthesis of hyperbranched cyclodextrin polymer (CDP) and to investigate their performance as drug carriers. In this study, β-Cyclodextrin (β-CD) was used as the basis for CDP nanocarriers, which were synthesized by reacting β-CD with pyromellitic dianhydride (PMDA) as a crosslinking agent. The effects of β-CD/PMDA molar ratio and reaction time were investigated to optimize the synthesis of CDP. The optimal reaction conditions were determined to be a reaction time of 2 h and a molar ratio of 1/12 β-CD/PMDA. Ketoprofen (KP) was used as a model drug to evaluate the loading capacity of CDP. The effects of KP/CDP (w/w) loading ratio, temperature, and stirring speed on the formation of the KP/CDP inclusion complex were investigated. The optimum conditions for loading KP into CDP were found to be 1/4 KP/CDP ratio, 4 h, 35 °C, and 300 rpm with a loading efficiency of 39.57%. Characterization of the CDP was performed using Zetasizer, FTIR, DSC, SEM and XRD analysis.

β-cyclodextrin polymer as tetrodotoxins scavenger in oyster extracts

Tetrodotoxins (TTXs) are potent marine neurotoxins involved in poisoning cases in humans after consumption of some marine organisms. A cell-based assay (CBA) providing toxicological information is a commonly used method for their detection because of its high sensitivity. However, matrix effects may interfere in the CBA. In this work, five insoluble cyclodextrin polymers, with different chemicals structures (βCDP-14-DS2, βCDP-13-DS2, βCDP-13-DS4, βCDP-14-DS4 and βCDP-N-DS5) have been investigated as novel clean-up materials for oyster extracts containing TTXs. The best recoveries have been achieved with βCDP-14-DS2 (∼100 %), which allowed exposing cells to 27-fold higher oyster matrix concentrations and decreased the LOQ down to 46 µg equiv. TTX/kg. Then, the applicability of this strategy has been demonstrated with oyster extracts from The Netherlands and comparing the results with immunoassay and liquid chromatography-tandem mass spectrometry (LC-MS/MS). This clean-up strategy combined with CBA could be implemented for TTXs detection in monitoring programs to ensure seafood safety.

The Lawson-loaded β-cyclodextrin nanocarriers (LB-NCs) a novel targeted cancer cell in stomach and breast cancer as a drug delivery system.

Applying nanotechnology to design drug delivery systems is a promising turning point in cancer treatment strategies. In the current study, Lawson, a nonpolar anticancer phytochemical, was entrapped into β-cyclodextrin polymer to evaluate its selective cytotoxicity in several types of human cancer cell lines including MCF-7, AGS, A549, and PC3. The Lawson-loaded β-cyclodextrin nanocarriers (LB-NCs) were produced by applying a high-energy ultrasound-mediated homogenization technique. The LB-NCs were characterized by applying dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), zeta potential, and field emission scanning electron microscopy (FESEM) analysis. Also, the selective cytotoxic impact of the LB-NCs was studied by conducting the MTT assay on human MCF-7, AGS, A549, and PC3 cancer cell lines. Finally, the type of cellular death was evaluated by measuring the cell cycle status and apoptotic gene expression profile of the treated MCF-7 cells by conducting flow cytometry and Q-PCR methods, respectively. The synthesized negatively charged (- 23.8 mV) nanoparticles (348.12 nm) exhibited apoptotic activity in the human breast MCF-7 cancer cells by upregulating the apoptotic gene expression profile (Caspase 3, 8, and 9). The LB-NCs exhibited a significant selective cytotoxic effect on the human cancer cell lines compared with the normal HUVEC cells. However, variable toxic intensities were detected depending on the cancer cell type. Selective cancer cell-depended anticancer activity of the produced LB-NCs has the potential to be considered their safe efficient targeted anticancer activity. However, studying the animal cancer models has to be conducted to verify their selective toxicity and clarify the cellular death mechanism.

A novel aminated Fe3O4/GO/carboxylated cross-linked β-CDP composite for effective sorption of cationic and anionic dyes from water

A novel adsorbent, aminated Fe3O4 (Fe3O4-NH2)/graphite oxide (GO)/carboxylated cross-linked β-cyclodextrin polymer (CDP-COOH) composite, was fabricated for influential removal of various types of dyes from waters. The morphology and structure of resulting Fe3O4-NH2/GO/CDP-COOH composite was studied by SEM, two-dimensional EDS map, FTIR, WAXD, XPS, TGA, and zeta potential meter, and its saturation magnetization was determined to be 46.3 emu/g by VSM. The maximal sorption capacities of Fe3O4-NH2/GO/CDP-COOH composite for methylene blue (MB, as a model of cationic dyes) and Congo red (CR, as a model of anionic dyes) at 303 K were 201.75 mg/g and 2211.05 mg/g, respectively, which can be mainly assigned to multiple adsorptive forces like electrostatic attractions, hydrogen bonds, host–guest self-assembly interactions, π-π electron cloud interactions, and Lewis acid-base interactions. The dye sorption by the Fe3O4-NH2/GO/CDP-COOH composite had a spontaneous nature according to the sorption thermodynamic calculation and can be well explained by pseudo-second-order model. The Langmuir and Freundlich models could explain the sorption isotherms of Fe3O4-NH2/GO/CDP-COOH composite for MB and GO, respectively. The Fe3O4-NH2/GO/CDP-COOH composite possessed many other advantages including the good sorption capability for different heavy metal ions (like Pb2+, Ni2+, and Cu2+) and organic compounds (like dichlorophenol and propranolol) as well as the good recyclability and reusability.

Studies on the Removal of Malachite Green from Its Aqueous Solution Using Water-Insoluble β-Cyclodextrin Polymers.

The rising global pollution of natural waters by dyes has brought to light the need for adaptable and efficient removal techniques. To create water-insoluble β-cyclodextrin (β-CD) polymers like CA/-CD, TA/-CD, and MA/-CD, several organic acids including citric acid (CA), tartaric acid (TA), and malic acid (MA) were cross-linked with β-cyclodextrin in this study. The obtained polymers were characterized by different advanced analytical techniques such as FTIR, SEM, and UV-vis spectrophotometry. Malachite green dye was removed from aqueous solutions using the synthesized polymers by adsorption. The adsorption investigation was conducted under several conditions, including pH, adsorbent mass, dye concentration, temperature, contact time, adsorption isotherm, and kinetics. The adsorbent CA/β-CD shows the highest adsorption of MG dye in all of the conditions because it contains a high number of carboxyl groups. The negatively charged carboxyl ions of CA/β-CD attract the positively charged MG dye electrostatically and remove MG from aqueous media with an efficiency of 91%. As a result, the findings indicated that water-insoluble polymers based on β-cyclodextrin are well-suited as inexpensive adsorbents to remove colors from aqueous media.

Human Serum Albumin Grafted by Monomeric and Polymeric β-Cyclodextrin as Drug Delivery System for Levofloxacin with Improved Pharmacological Properties

Human serum albumin (HSA) is a multifunctional protein, known to be a natural carrier for a number of endogenous and exogenous compounds, including drugs. HSA-based drugs formulation is a clinically validated approach to improve pharmacological properties and biodistribution (such as in Abraxane). Based on this, one might like to modify HSA in a way that its distribution is more favorable for certain therapeutic purposes. Levofloxacin (LV), a broad-spectrum antibiotic drug, could benefit from extended systemic exposure, and stronger interactions with plasma proteins could be useful for this purpose. We engrafted monomeric or polymeric cyclodextrins (CDs) on the surface of HSA molecules to strengthen the LV adsorption (the CD−LV dissociation constant is three orders of magnitude lower than that of HSA−LV). We found that (HSA−HPolS)conj+LV exhibited the highest activity against E. coli, whereas (HSA−HPCD)conj+LV was the most effective against B. subtilis, and both HSA conjugates were more potent than LV alone or LV with HSA. Further fine-tuning of HSA could yield an improvement in biodistribution and thus a more favorable risk/benefit ratio.

Cyclodextrin Polymer-Loaded Micro-Ceramic Balls for Solid-Phase Extraction of Triazole Pesticides from Water.

A citric acid cross-linked β-cyclodextrin (β-CD) polymer was synthesized and loaded on micro-ceramic balls to fabricate the solid-phase adsorbents (P-MCB) for adsorption and extraction of triazole pesticides from water. The stability of β-CD polymer and P-MCB was investigated in solutions with different pH values at different temperatures. The adsorption properties and the influence of kinetics, sorbent amount, pesticide concentration, and temperature on the adsorption capacity were evaluated. The results showed P-MCB had favorable adsorption of 15.98 mg/g flutriafol in 3.5 h. The equilibrium data followed the Freundlich equation, and the adsorption of flutriafol and diniconazole followed the second-order kinetics. The recovery rate of P-MCB for triazole pesticides in water was satisfactory, and the recovery rate was still 80.1%, even at the 10th cycle. The P-MCB had good stability, with a degradation rate of 0.2% ± 0.08 within 10 days, which could ensure extraction and recycling.

Porous β-cyclodextrin polymer microspheres for iodine adsorption from aqueous solution

Porous β-cyclodextrin polymer microspheres for iodine adsorption from aqueous solution

Efficient and rapid capture of uranium(VI) in wastewater via multi-amine modified β-cyclodextrin porous polymer

Efficient and rapid capture of uranium(VI) in wastewater via multi-amine modified β-cyclodextrin porous polymer

Copolymerized Polymers Based on Cyclodextrins and Cationic Groups Enhance Therapeutic Effect of Rebamipide in the N-Acetylcysteine-Treated Dry Eye Model.

We aimed to prepare a β-cyclodextrin (β-CD) polymer using radical polymerization with co-monomers, 6-deoxy-6-(2-methacryloyloxyethylsuccinamide)-β-cyclodextrin (CD-MSAm) and N,N,N-trimethyl-N-(2-hydroxy-3-metacryloyloxopropyl)-ammonium chloride (QA) to design cyclodextrins suitable for use in ophthalmology. In addition, we evaluated their solubility and inclusion properties with rebamipide (REB), a poorly soluble drug, and investigated the usefulness of the β-CD polymer and REB (REB@CDQA) combination in treating dry eye. The β-CD polymer (CD-MSAm-co-QA, CDQA) based on CD-MSAm/QA was prepared via radical polymerization, and the usefulness of REB@CDQA in treating dry eye was evaluated using a rabbit treated with N-acetylcysteine (dry eye model). The solubility of the CDQA powder was higher than that of the β-CD powder, and 80 nm colloids were observed in the CDQA solution. No corneal toxicity was observed in human corneal epithelial cells or rat corneas treated with 0.2% CDQA solution. The levels of REB dissolved in the CDQA solution were higher than those of the β-CD solution. Moreover, the application of the CDQA solution enhanced REB retention in the cornea and attenuated the transcorneal penetration of REB. In addition, instillation of REB@CDQA enhanced the volume of the lacrimal fluid and normalized the reduced mucin levels in the dry eye model. The extent of tear film breakup was attenuated by REB@CDQA instillation. The CDQA solution enhanced the solubility of REB, and the combination of CDQA and REB enhanced the drug content in the corneal tissue. Moreover, the therapeutic effect on dry eye was higher than that of REB suspensions without CDQA.