Β-cyclodextrin Polymer Research Articles

Enhanced degradation of sulfamethoxazole by a modified nano zero-valent iron with a β-cyclodextrin polymer: Mechanism and toxicity evaluation

Rising concern about emerging and already persisting pollutants in water has urged the scientific community to develop novel remedial techniques. A new group of remediation methods is based on the modification of nanoscale zero-valent iron particles (nZVI), which are well known for treating volatile organic compounds and heavy metals. The properties of nZVI may be further enhanced by modifying their structure or surface using “green” polymers. Herein, nZVI was modified by a β-cyclodextrin polymer (β-CDP), which is considered an environmentally safe and inexpensive adsorbent of contaminants. This composite was used for the first time for the degradation of sulfamethoxazole (SMX). Coating by β-CDP not only enhanced the degradation of SMX (>95%, under 10 min) by the nanoparticles in a wide pH range (3–9) and enabled their efficient reusability (for three cycles) but also made the coated nZVI less toxic to the model bioindicator microalga Raphidocelis subcapitata. Moreover, degradation products of SMX were found to be less toxic to Escherichia coli bacteria and R. subcapitata microalga, contrary to the SMX antibiotic itself, indicating a simple and eco-friendly cleaning process. This research aims to further stimulate and develop novel remedial techniques based on nZVI, and provides a potential application in the degradation of antibiotics in a wide pH range. Moreover, the wealth of available cyclodextrin materials used for surface modification may open a way to discover more efficient and attractive composites for environmental applications.

Design of a hydrophilic mercaptosuccinic acid-functionalized β-cyclodextrin polymer via host-guest interaction: toward highly efficient glycopeptide enrichment.

A hydrophilic interaction chromatography (HILIC) strategy is considered as an efficient strategy for efficient glycopeptide enrichment. Here, a novel hydrophilic material (denoted as magCDP@Ada-MSA) was constructed through host-guest interaction between crosslinked β-cyclodextrin (β-CD) polymers and mercaptosuccinic acid (MSA) derived adamantane. On the one hand, crosslinked β-CD polymers have great hydrophilicity due to their abundant hydrophilic hydroxyl groups. On the other hand, the hydrophilic functional molecule MSA was introduced into crosslinked β-CD polymers through host-guest interaction for further hydrophilic modification of the material. Hydroxyl groups in crosslinked β-CD polymers and carboxyl groups in MSA together endow the material with excellent hydrophilicity and good affinity toward glycopeptides. The prepared hydrophilic material demonstrated rapid magnetic separation (within 5 s) and reusability (at least 10 cycles). Thanks to the above advantages, magCDP@Ada-MSA showed satisfactory performance for the specific enrichment of glycopeptides (selectivity, 1 : 500 molar ratios of HRP/BSA and sensitivity, 0.1 fmol μL-1). Moreover, magCDP@Ada-MSA was successfully applied for selective glycopeptide enrichment from complex biological samples (human serum and saliva).

Cyclodextrin/Adamantane-Grafted Polyethylene Glycol–Based Self-assembling Constructs for Topical Delivery of Ketorolac Tromethamine: Formulation, Characterization, and In Vivo Studies

Topical formulation of non-steroidal anti-inflammatory drugs (NSAIDs) exhibits many advantages over the oral administration route, such as avoiding the direct effect on GIT and avoiding the poor oral bioavailability of such drugs. Our study aims to develop a new self-assembling construct based on the hydrophobic interaction between adamantane terminated poly (ethylene glycol) polymers and polymerized β-cyclodextrin. The viscous constructs were developed from direct mixing of host and guest polymer solutions, indicating spontaneous formation without cross-linkers. The modified system was evaluated by different analyses, including X-ray diffractometry, electron microscopy, isothermal titration calorimetry, and rheological analysis. Moreover, such a system's ability for drug loading and release was investigated via the in vitro release of ketorolac tromethamine (KT) as a model of NSAIDs. Finally, the prepared formulas were applied on a rat paw edema model to prove the enhanced anti-inflammatory activities. The obtained results indicated that the modified constructs have a rubbery porous structure with an amorphous nature. Also, from rheological results, the modified system exhibited a viscous behavior with higher loss modulus (G″) compared with storage (G'). The inclusion complexation between cyclodextrin and adamantane moieties was proved by the recorded high binding constants with a 1:1 stoichiometric ratio. Furthermore, the results showed the successful KT incorporation into the modified system and quantitatively released through a semi-permeable membrane in a sustained fashion (over 24 h). Finally, the in vivo results of the medicated constructs showed a significant inhibition of the induced inflammation and swelling, indicating that the modified construct has a great utility for safe non-irritating topical delivery applications.

Phosphate-crosslinked β-cyclodextrin polymer for highly efficient removal of Pb(ii) from acidic wastewater

Novel phosphate-crosslinked β-cyclodextrin polymer was synthesized for highly efficient Pb(ii) removal from acidic wastewater.

Efficient Adsorption of Bpa and Pb2+ by Sulfhydryl-Rich Β-Cyclodextrin Polymers

Efficient Adsorption of Bpa and Pb2+ by Sulfhydryl-Rich Β-Cyclodextrin Polymers

Adsorptive removal of uranium(vi) from wastewater using a crosslinked amidoxime-functionalized β-cyclodextrin polymer

A crosslinked amidoxime β-CDP-AO was applied to adsorptive removal of radioactive U(vi) from wastewater.

Study of a water-soluble supramolecular complex of curcumin and β-cyclodextrin polymer with electrochemical property and potential anti-cancer activity

As a member of the curcuminoid compound family, curcumin (Cur) has many interesting therapeutic properties. However, its low aqueous solubility and stability have resulted in poor bioavailability and restricted clinical efficacy. Based on size matching, β-cyclodextrin polymer (β-CDP), with its hydrophilic polymer chains and hydrophobic cavities, can form an inclusion complex with Cur. To improve the water solubility and stability of Cur, a simple and eco-friendly grinding method was designed to form β-CDP inclusion complexes. According to the Boltzmann–Hamel's method and Job's method, the molar ratio of the β-CD unit in β-CDP to Cur was determined to be 1:1. The diffusion coefficient and diffusion activation energy of Cur-β-CDP were calculated in an electrochemical study. This supramolecular complex worked well in vitro to inhibit the proliferation of hepatoma carcinoma cells HepG2. Remarkably, this method visibly reduced the undesirable side effects on normal cells, without weakening the anti-cancer activity of the drugs. We expect that the obtained host–guest complex will provide a new approach for delivering natural drug molecules, having low water solubility.

Identifying the physicochemical properties of β-cyclodextrin polymers that determine the adsorption of perfluoroalkyl acids

Cyclodextrin polymers (CDPs) are emerging adsorbents with demonstrated potential to remove perfluoroalkyl acids (PFAAs) from water. However, little is known about how the physicochemical properties of different types of CDPs determine PFAA adsorption on CDPs. In this study, we investigated the adsorption performance of 34 CDPs which consist of 14 different crosslinkers and exhibit a wide range of physicochemical properties. The performance metrics included adsorption kinetics, equilibrium adsorption density, and adsorption affinity for six PFAAs. We then used complementary bivariate and multivariate analyses to discover relationships between sixteen measurable physicochemical properties of the CDPs and their performance as adsorbents. We found that: (1) CDPs with a less negative or more positive surface charge will exhibit enhanced adsorption of all types of PFAAs; (2) CDPs with greater porosity and surface area will exhibit enhanced adsorption kinetics for all types of PFAAs; (3) CDPs with greater crosslinker content will exhibit enhanced adsorption of short-chain PFAAs; (4) CDPs containing more hydrophobic crosslinkers will exhibit enhanced equilibrium adsorption density and adsorption affinity for longer-chain PFAAs; and (5) CDPs with smaller particle sizes will exhibit enhanced adsorption kinetics and equilibrium adsorption density for all PFAAs. These insights will enable the further development of CDPs and other novel adsorbents to optimize their performance for removing PFAAs during water and wastewater treatment or groundwater remediation.

Design and synthesis of a star-like polymeric micelle modified with AS1411 aptamer for targeted delivery of camptothecin for cancer therapy

Improving of tumor targeting and decreasing side effects at normal cells of antitumor drugs are necessary to promote the cancer chemotherapy efficacy. Herein, we have synthesized a novel 21-arm star like diblock polymer of β-cyclodextrin-{poly(ε-caprolactone)-poly(2-aminoethylmethacrylate)}21 which decorated with nucleolin aptamer (AS1411). The diblock polymer was prepared by combined ROP with electron transfer atom transfer radical polymerization (ARGET ATRP) methods followed camptothecin (CPT) encapsulation with high entrapment efficiency (65%). Subsequently, the attachment of AS1411 aptamer via covalent bond led to the formation of the final product β-CD-(PCL-PAEMA)21/AS1411/CPT. In vitro drug release experiment demonstrated almost 50% of CPT was released in 72 h at acidic tumoral environment. The data of cellular toxicity (MTT) showed that the final product remarkably enhanced cell death in MCF-7 and 4T1 cells while normal cells (L929) showed high viability toward the prepared complex. Also, the finding of flow cytometry analysis and fluorescence imaging indicated successful internalization of complex into the target cells but not the nontarget cells. The in vivo experiments revealed the fact that β-CD-(PCL-PAEMA)21/AS1411/CPT micelles showed high tumor inhibitory potential in comparison with free CPT. These findings exhibited the excellent ability of the novel star-like polymeric micelle with targeting agent for the targeted and effective delivery of CPT in cancer treatment.

Ultra-rapid and highly efficient enrichment of organic pollutants via magnetic mesoporous nanosponge for ultrasensitive nanosensors

Currently, owing to the single-molecule-level sensitivity and highly informative spectroscopic characteristics, surface-enhanced Raman scattering (SERS) is regarded as the most direct and effective detection technique. However, SERS still faces several challenges in its practical applications, such as the complex matrix interferences, and low sensitivity to the molecules of intrinsic small cross-sections or weak affinity to the surface of metals. Here, we show an enrichment-typed sensing strategy with both excellent selectivity and ultrahigh detection sensitivity based on a powerful porous composite material, called mesoporous nanosponge. The nanosponge consists of porous β-cyclodextrin polymers immobilized with magnetic NPs, demonstrating remarkable capability of effective and fast removal of organic micropollutants, e.g., ~90% removal efficiency within ~1 min, and an enrichment factor up to ~103. By means of this current enrichment strategy, the limit of detection for typical organic pollutants can be significantly improved by 2~3 orders of magnitude. Consequently, the current enrichment strategy is proved to be applicable in a variety of fields for portable and fast detection, such as Raman and fluorescent sensing.

Synthesis of reusable cyclodextrin polymers for removal of naphthol and naphthylamine from water.

As one group of important naphthalene derivatives, naphthol and naphthylamine are diffusely employed as dye intermediates. The presence of naphthol and naphthylamine in water systems may pose risks to the environment and public health due to their carcinogenicity. In this study, four mesoporous polymers prepared by β-cyclodextrin derivatives and tetrafluoroterephthalonitrile were obtained and applied to adsorbing 1-naphthylamine, 2-naphthylamine, 1-naphthol, and 2-naphthol from water. The impact of adsorption time, initial concentration of naphthol and naphthylamine, and temperature on the adsorption efficiency of the four polymers were explored separately. The four polymers present fast adsorption kinetics toward naphthol and naphthylamine, attaining 93 ~ 100% of adsorption equilibrium uptake for 1-naphthol, 1-naphthylamine, 2-naphthylamine in 15min, and 87 ~ 90% of equilibrium uptake for 2-naphthol in 15min. The kinetics could be depicted well by the pseudo-second-order kinetic model. The adsorption isotherms of the four polymers toward naphthol and naphthylamine accord with the Redlich-Peterson or Sips model. The maximum adsorption capacities of 1-naphthylamine, 2-naphthylamine, 1-naphthol, and 2-naphthol are 189.9mg/g, 82.8mg/g, 137.7mg/g, and 88.7mg/g, respectively. The adsorption ratio increases fast with reducing the initial concentration of naphthol and naphthylamine, and the adsorption ratio of naphthol and naphthylamine in 5mg/L can achieve over 95% in 25°C. In addition, the four polymers can be effortlessly regenerated by a gentle and simple washing procedure with little reduction in performance. The adsorption performance of the four polymers toward the four naphthalene derivatives can be improved by increasing the adsorption temperature. In conclusion, the prepared β-cyclodextrin polymers exhibit rapid water treatment in removing the four low-concentration naphthalene derivatives with convenient regeneration and good reusability.

Silver-Modified β-Cyclodextrin Polymer for Water Treatment: A Balanced Adsorption and Antibacterial Performance

Water pollution caused by organic pollutants and pathogenic microorganism is a critical issue. In this study, we reported a silver-modified β-cyclodextrin polymer (CD-CA/PDA-Ag) used for the removal of dyes and the suppression of microorganisms from water. In order to avoid silver nanoparticles agglomeration, the material was first coated with polydopamine (PDA) on β-cyclodextrin matrix, whose reducing catechol groups subsequently immobilized silver ions in situ to form uniformly dispersed silver nanoparticles. CD-CA/PDA-0.5Ag displayed a high adsorption capacity of methylene blue (535.93 mg/g), which is mainly attributed to electrostatic interactions, host-guest inclusions and π-π bond stacking effects. Furthermore, both diffusion inhibition zone tests and colony formation unit tests were investigated, which showed excellent antimicrobial capability on Escherichia coli (E. coli) and Staphylococcus aureus (S. auerus). Overall, CD-CA/PDA-Ag proved to have an excellent adsorption capacity and antibacterial performance, which provides a great potential in water purification.

Preformulation Studies and Bioavailability Enhancement of Curcumin with a 'Two in One' PEG-β-Cyclodextrin Polymer.

Drug delivery systems are used to improve the biopharmaceutical properties of curcumin. Our aim was to investigate the effect of a water-soluble ‘two in one’ polymer containing covalently bonded PEG and βCD moieties (βCPCD) on the solubility and bioavailability of curcumin and compare it to a polymeric β-cyclodextrin (βCDP) cross-linked with epichlorohydrin. Phase-solubility and dynamic light scattering (DLS) experiments showed that the solubility of curcumin increased significantly in 10 m/m % βCPCD and βCDP solutions, but βCPCD–curcumin particles had higher hydrodynamic volume. The formation of the βCPCD–curcumin complex in solution and sedimented phase was confirmed by NMR spectroscopy. Biocompatibility and permeability experiments were performed on Caco-2 cells. Polymers did not show cytotoxicity up to 10 m/m % and βCPCD significantly increased the permeability of curcumin. DLS measurements revealed that among the interaction of polymers with mucin, βCPCD formed bigger aggregates compared to βCDP. Curcumin complexes were lyophilized into capsules and structurally characterized by micro-CT spectroscopy. Drug release was tested in a pH 1.2 medium. Lyophilized complexes had a solid porous matrix and both βCPCD and βCDP showed rapid drug release. βCPCD provides an opportunity to create a swellable, mucoadhesive matrix system for oral drug delivery.

Cyclodextrin Polymers as Delivery Systems for Targeted Anti-Cancer Chemotherapy

In the few last years, nanosystems have emerged as a potential therapeutic approach to improve the efficacy and selectivity of many drugs. Cyclodextrins (CyDs) and their nanoparticles have been widely investigated as drug delivery systems. The covalent functionalization of CyD polymer nanoparticles with targeting molecules can improve the therapeutic potential of this family of nanosystems. In this study, we investigated cross-linked γ- and β-cyclodextrin polymers as carriers for doxorubicin (ox) and oxaliplatin (Oxa). We also functionalized γ-CyD polymer bearing COOH functionalities with arginine-glycine-aspartic or arginine moieties for targeting the integrin receptors of cancer cells. We tested the Dox and Oxa anti-proliferative activity in the presence of the precursor polymer with COOH functionalities and its derivatives in A549 (lung, carcinoma) and HepG2 (liver, carcinoma) cell lines. We found that CyD polymers can significantly improve the antiproliferative activity of Dox in HepG2 cell lines only, whereas the cytotoxic activity of Oxa resulted as enhanced in both cell lines. The peptide or amino acid functionalized CyD polymers, loaded with Dox, did not show any additional effect compared to the precursor polymer. Finally, studies of Dox uptake showed that the higher antiproliferative activity of complexes correlates with the higher accumulation of Dox inside the cells. The results show that CyD polymers could be used as carriers for repositioning classical anticancer drugs such as Dox or Oxa to increase their antitumor activity.

Passive sampling of chlorophenols in water and soils using diffusive gradients in thin films based on β-cyclodextrin polymers

Chlorophenols (CPs) have been listed as priority control pollutants because of their high toxicity and wide range. An In-situ monitoring technique using diffusive gradients in thin films based on porous β-cyclodextrin polymers as binding materials (CDP-DGT), was established to monitor four typical CPs, namely, 4-Chlorophenol (4-CP), 2,4-Dichlorophenol (2,4-DCP), 2,4,5-Trichlorophenol (2,4,5-TCP), 2,4,6-Trichlorophenol (2,4,6-TCP) in water and soils. The performance of CDP-DGT are stable under the conditions of pH 3.5–9.3, ionic strength 0.001–0.500 mol L−1 and dissolved organic matter concentration 0–20 mol L−1. The adsorption capacities of CDP-DGT for 4-CP, 2,4-DCP, 2,4,5-TCP, 2,4,6-TCP were 57.80 μg cm−2, 98.82 μg cm−2, 95.69 μg cm−2 and 98.91 μg cm−2, respectively. The time-average weighted concentrations of four CPs determined by CDP-DGT at Sanjiangkou wharf (Yangtze river, China) were consistent with the results of grab sampling, indicating the feasibility of CDP-DGT application in actual water. In addition, the distribution of CPs in the red soil of Kunming and paddy soil of Yixing were also studied by CDP-DGT, and the desorption kinetics in the two soils were analyzed with the DIFS model. The higher the soil organic matter content is, the more CPs are distributed in the soil solid phase. CPs in both soils can be partially resupplied to soil solution from the soil solid phase and the higher the partition coefficient for labile CPs is, the stronger the supplement capacity is.

Porous multifunctional phenylcarbamoylated-β-cyclodextrin polymers for rapid removal of aromatic organic pollutants.

In this work, polymers containing a large number of benzene rings and multiple functional groups were designed to remove aromatic organic pollutants. Using tetrafluoroterephthalonitrile (TFTPN) as a rigid crosslinking agent to crosslink different functionalized phenylcarbamoylated-β-cyclodextrin derivatives to prepare a series of porous multifunctional cyclodextrin (CD) polymerizations, including three preliminary polymerized adsorption materials and a mix β-cyclodextrin polymer (X-CDP) prepared via a secondary crosslinking procedure of the above three materials. The X-CDP preparation process connects the pre-formed nanoparticles and increases the presence of linkers inside the particles. At the same time, X-CDP exhibited porous structure with various functional groups such as nitro, chlorine, fluorine, and hydroxyl. Those special characteristics render this material with good adsorption ability towards various aromatic organic pollutants in water, including tetracycline, ibuprofen, dichlorophenol, norfloxacin, bisphenol A, and naphthol. Especially, the maximum adsorption capacity for tetracycline at equilibrium reached 110.56 mg·g-1, which is competitive with the adsorption capacities of other polysaccharide adsorbents. X-CDP removed organic contaminants much more quickly than other adsorbents, reaching almost ~95% of its equilibrium in only 30 s, and the rate constant reaches 2.32 g·mg-1·min-1. The main adsorption process of the pollutants by X-CDP fitted the pseudo-second-order kinetic and Langmuir isotherm well, indicating that the adsorption process is monolayer adsorption. Moreover, X-CDP possessed the good reusability where the pollutant removal rate was only reduced 8.3% after five cycles. Such advantages render the polymer great potential in the rapid treatment of organic pollutants in water bodies.

Effective retention of radioactive Cs+ and Ba2+ ions using β-cyclodextrin functionalized diatomite (β-CD/D) as environmental adsorbent; characterization, application, and safety

The siliceous frustules of diatomite were integrated with β-cyclodextrin polymer in novel composite (β-CD/D) for enhanced retention properties for radioactive ions. The β-CD/D composite was characterized by different analytical techniques and applied in batch adsorption studies for the dissolved Cs+ and Ba2+ ions. The β-CD/D composite exhibits promising retention capacities (Cs+ (144.5 mg/g) and Ba2+ (195.7 mg/g)) which are higher than its components and other evaluated adsorbent in literature. The Cs+ and Ba2+ retention reactions by β-CD/D are of Langmuir properties, Pseudo-Second order kinetics, and Gaussian energies less than 8 KJ/mol. Therefore, the ions were adsorbed homogeneously in monolayer forms by physicochemical mechanisms involved in electrostatic attraction and the formation of chemical complexes. The thermodynamic parameters suggested spontaneous and exothermic behaviors for the occurred Cs+ and Ba2+ retention reactions. The synthetic β-CD/D is of significant affinities for the Cs+ and Ba2+ ions in the presence of competitive anions (HCO3−, SO42−, NO3−, and PO43−) and considerable affinitive in the presence of other metals (Cd2+, Pb2+, Zn2+, and Co2+). The β-CD/D composite also is a highly recyclable product and can be reused effectively in Cs+ and Ba2+ removal processes for five cycles.

Gelation Based on Host-Guest Interactions Induced by Multi-Functionalized Nanosheets.

Host–guest interaction, being reversible and stimuli-responsive, is ideal to be applied to the design of hydrogels. We created a gelation system based on the host–guest interactions between the adamantyl groups and β-cyclodextrin (β-CD) polymer. N,N,N-trimethyl-1-adamantylammonium hydroxide (TriMAA) cations were attached to the pre-exfoliated α-zirconium phosphate (α-ZrP) nanosheets by ionic bonding through a displacement reaction with the exfoliating agents. The exfoliated α-ZrP nanosheets with adamantyl groups directly or indirectly attached to the surface act as reversible high-functionality crosslinkers within the β-CD polymer. The gelation occurred at a host-to-guest ratio of 1:10 or 1:5 at room temperature within minutes. The agents used to exfoliate α-ZrP can tailor the surface of the resultant α-ZrP nanosheets and the ionic strength of the system, which directly affects the further gelation results. Plus, the exfoliating agent cations may generate a host-and-guest interaction with the β-CD polymer as well. This gelation process without covalent bonding formation should help fellow researchers to better understand the gelation system and host–guest interactions.

Surface functionalization of natural hydroxyapatite by polymerization of β-cyclodextrin: application as electrode material for the electrochemical detection of Pb(II).

A composite material prepared by polymerization of β-cyclodextrin (β-CD) on the surface of natural hydroxyapatite using citric acid as cross linker, was employed as electrode material for the detection of Pb(II). Hydroxyapatite was obtained from bovine bones, following a three-step procedure including pre-calcination, chemical treatment with (NH4)2HPO4, and calcination. The structure and morphology of the pristine hydroxyapatite (NHAPP0.5) and its functionalized counterpart (NHAPp0.5-CA-β-CD) were examined using XRD, FTIR, and SEM. Upon deposition as thin film on a glassy carbon electrode (GCE), the ion exchange ability of NHAPp0.5-CA-β-CD was exploited to elaborate a sensitive sensor for the detection of lead. The electroanalytical procedure was based on the chemical accumulation of Pb(II) ions under open-circuit conditions, followed by the detection of the preconcentrated species using differential pulse anodic stripping voltammetry. The reproducibility of the proposed method, based on a series of 8 measurements in a solution containing 2 μM Pb(II) gave a coefficient of variation of 1.27%. Significant parameters that can affect the stripping response of Pb(II) were optimized, leading to a linear calibration curve for lead in the concentration range of 2 × 10-8 mol L-1 - 20 × 10-8 mol L-1 (R2 = 0.998). The detection limit (3S/m) and the sensitivity of the proposed sensor were 5.06 × 10-10 mol L-1 and 100.80 μA.μM-1, respectively. The interfering effect of several ions expected to affect the determination of lead was evaluated, and the proposed sensor was successfully applied in the determination of Pb(II) ions in spring water, well water, river water and tap water samples.

A supramolecular host-guest interaction-mediated injectable hydrogel system with enhanced stability and sustained protein release

Injectable hydrogels have been studied as drug delivery systems because of their minimal invasiveness and sustained drug release properties. Pluronic F127, consisting of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) triblock copolymers, exhibits thermo-responsive properties and hence is injectable due to its rapid sol-gel transition. Unmodified Pluronic F127-based hydrogels, however, have limited long-term stability and controllable release of drugs entrapped within them. In this study, host-guest interactions between adamantane-conjugated Pluronic F127 (F127-Ad) and polymerized β-cyclodextrin (CDP) were employed to develop a hydrogel-based protein delivery system. Single or multiple adamantane units were successfully introduced at the termini of Pluronic F127 with a 100% conversion yield, and the synthesized F127-Ad polymer produced a physically crosslinked micelle-packing structure when mixed with CDP. As the number of adamantanes at the terminal ends of Pluronic F127 increased, the critical gelation concentration of F127-Ad/CDP hydrogel decreased from 15 to 6% (w/v). The F127/CDP hydrogel was able to maintain its structure even with lower polymer content, and its injectability improved with a reduction of the hydrogel viscosity. The long-term stability of F127/CDP hydrogels was evaluated in vitro and in vivo, and it was demonstrated that the subcutaneously injected hydrogel did not disintegrate for up to 30 d. Throughout the drug release test using gelatin and insulin as model drugs, it was demonstrated that their release rates could be regulated via complexation between the protein drugs and the β-cyclodextrin molecules inside the hydrogel. In conclusion, the F127-Ad/CDP hydrogel is expected to be a versatile protein delivery system with controllable durability and drug release characteristics. Statement of significancePluronic F127 is one of the widely studied polymeric materials for thermo-sensitive injectable hydrogels due to its high biocompatibility and rapid sol-gel transition. Since the Pluronic F127-based hydrogel has some limitations in its long-term stability and mechanical property, it is inevitable to modify its structure for the application to drug delivery. In this study, mono- or multi- adamantane-conjugated Pluronic F127s were synthesized and mixed with β-cyclodextrin polymers to form hydrogels with host-guest interaction-mediated micelle-packing structures. The host-guest interaction introduced into the hydrogel system endowed it a sustained protein drug release behavior as well as high durability in vitro and in vivo. By increasing the number of adamantane molecules at the end of the Pluronic F127, both the stability and injectability of the hydrogel could be also modulated.