CD-based Polymers Research Articles

Cyclodextrins and Their Polymers Affect Human Serum Albumin's Interaction with Drugs Used in the Treatment of Pulmonary Infections.

Respiratory infectious diseases have challenged medical communities and researchers. Ceftriaxone, meropenem and levofloxacin are widely used for bacterial infection treatment, although they possess severe side effects. To overcome this, we propose cyclodextrin (CD) and CD-based polymers as a drug delivery system for the drugs under consideration. CD polymers demonstrate higher binding affinity for levofloxacin (Ka ≈ 105 M) compared to drug-CD complexes. CDs slightly alter the drugs' affinity for human serum albumin (HSA), whereas CD polymers increase the drugs' binding affinity up to 100 times. The most significant effect was observed for more the hydrophilic drugs ceftriaxone and meropenem. The drug's encapsulation in CD carriers leads to a decrease in the degree of change in the protein's secondary structure. The drug-CD carrier-HSA complexes demonstrate satisfying antibacterial activity in vitro, and even a high binding affinity does not decrease the drug's microbiological properties after 24 h. The proposed carriers are promising for a drug form with a prolonged drug release.

Cyclodextrin-Based Polymeric Drug Delivery Systems for Cancer Therapy

Cyclodextrins (CDs) are one of the most extensively studied cyclic-oligosaccharides due to their low toxicity, good biodegradability and biocompatibility, facile chemical modification, and unique inclusion capacity. However, problems such as poor pharmacokinetics, plasma membrane disruption, hemolytic effects and a lack of target specificity still exist for their applications as drug carriers. Recently, polymers have been introduced into CDs to combine the advantages of both biomaterials for the superior delivery of anticancer agents in cancer treatment. In this review, we summarize four types of CD-based polymeric carriers for the delivery of chemotherapeutics or gene agents for cancer therapy. These CD-based polymers were classified based on their structural properties. Most of the CD-based polymers were amphiphilic with the introduction of hydrophobic/hydrophilic segments and were able to form nanoassemblies. Anticancer drugs could be included in the cavity of CDs, encapsulated in the nanoparticles or conjugated on the CD-based polymers. In addition, the unique structures of CDs enable the functionalization of targeting agents and stimuli-responsive materials to realize the targeting and precise release of anticancer agents. In summary, CD-based polymers are attractive carriers for anticancer agents.

Cyclodextrin-Based Polymeric Materials Bound to Corona Protein for Theranostic Applications.

Cyclodextrins (CDs) are cyclic oligosaccharide structures that could be used for theranostic applications in personalized medicine. These compounds have been widely utilized not only for enhancing drug solubility, stability, and bioavailability but also for controlled and targeted delivery of small molecules. These compounds can be complexed with various biomolecules, such as peptides or proteins, via host-guest interactions. CDs are amphiphilic compounds with water-hating holes and water-absorbing surfaces. Architectures of CDs allow the drawing and preparation of CD-based polymers (CDbPs) with optimal pharmacokinetic and pharmacodynamic properties. These polymers can be cloaked with protein corona consisting of adsorbed plasma or extracellular proteins to improve nanoparticle biodistribution and half-life. Besides, CDs have become famous in applications ranging from biomedicine to environmental sciences. In this review, we emphasize ongoing research in biomedical fields using CD-based centered, pendant, and terminated polymers and their interactions with protein corona for theranostic applications. Overall, a perusal of information concerning this novel approach in biomedicine will help to implement this methodology based on host-guest interaction to improve therapeutic and diagnostic strategies.

Mechanochemical synthesis of reticular β-cyclodextrin polyurethanes for the decontamination of phenolic micropollutants

Cyclodextrin-based porous polymers have become a kind of promising adsorbents for the remediation of wastewater by virtue of their sustainability and economic potential. The acquisition of aforementioned adsorbents commonly requires elaborate preparation procedures which involve organic solvent, catalyst, inert atmosphere, or long reaction time. Herein, a facile and scalable solid-state mechanochemical approach was developed to afford reticular β-cyclodextrin polyurethanes (CDPUs) in a short time (2 h) without any organic solvents and catalysts at ambient conditions. Various diisocyanates can be used as coupling agents to link β-CD molecules into CDPUs relying on the driving force of ball milling. CDPUs-based composites can be also successfully synthesized via a “one-pot” mechanochemical reaction. The afforded CDPUs exhibit nearly the same physiochemical characteristics as those synthesized in solvents or with the assistance of catalyst. CDPUs have numerous accessible active adsorption sites, including β-CD cavities, bridging urethane groups, dangling amino groups, and aromatic rings. Owing to the accessible porosities and abundant adsorption sites, CDPUs exhibited rapid adsorption rate and high adsorption capacity towards phenolic micropollutants. CDPUs can maintain adsorption efficiency in a wide pH range, ionic strength, and humic acid. There is no significant decrease of adsorption efficiency for more than eight regeneration cycles, indicating their suitability for practical water treatment. This solid-state mechanochemical synthesis method for reticular CD-based polymers paves a new insight into green preparation of adsorbents and their sustainable use for the practical remediation of micropollutant wastewater.

Efficient removal of thiophenic sulfides from fuel by micro-mesoporous 2-hydroxypropyl-β-cyclodextrin polymers through synergistic effect

Efficient removal of thiophenic sulfides is important for the purification of fuel. Herein, 2-hydroxypropyl-β-cyclodextrin polymers (2-HP-β-CDPs) with micro-mesopores are synthesized using 2-HP-β-CD and tetrafluoroterephthalonitrile (TFTPN) for removing thiophenic sulfides. The cross-linking of 2-HP-β-CD and TFTPN units forms the mesopores, and the cyclodextrin cavity acts as the micropores. The 2-HP-β-CDP1:4 (1:4 is the molar ratio of 2-HP-β-CD and TFTPN in preparation) possesses a surface area of 197.49 m2 g–1, and most of pores are at 1.09 nm of micropores and 6.06 nm of mesopores. The synergistic effect of the micro-mesopores promotes 2-HP-β-CDP1:4 to remove the thiophenic sulfides in the order of benzo[b]thiophene > 4,6-dimethyldibenzothiophene ≈ dibenzothiophene > thiophene. The removal efficiency and rate using 2-HP-β-CDP1:4 are better than those of CD-based and most traditional adsorbents that have been reported. Most of sulfides adsorbed by mesopores diffuse rapidly to micropores from the wide end of cyclodextrin and then are selectively captured by the cyclodextrin units in 2-HP-β-CDP1:4. These findings can guide the synthesis of CD-based polymers and the application of fuel purification.

Recent Advances of Porous Materials Based on Cyclodextrin

Porous materials have attracted significant attention because of their rising applications in many fields. Cyclodextrins (CDs) are suitable building units in the fabrication of porous materials owing to their intrinsic nanoporous structure, easy modification, and biocompatibility, which may result in the formation of CD-based organic frameworks (including cyclodextrin metal-organic frameworks (CD-MOFs) and cyclodextrin covalent organic frameworks (CD-COFs)), and CD-based polymer hybrid porous materials. This review focuses on the recent progress in the fabrication and applications of CD-based porous materials with novel structures and functionalities.

Cyclodextrin Monomers and Polymers for Drug Activity Enhancement.

Cyclodextrins (CDs) and cyclodextrin (CD)-based polymers are well-known complexing agents. One of their distinctive features is to increase the quantity of a drug in a solution or improve its delivery. However, in certain instances, the activity of the solutions is increased not only due to the increase of the drug dose but also due to the drug complexation. Based on numerous studies reviewed, the drug appeared more active in a complex form. This review aims to summarize the performance of CDs and CD-based polymers as activity enhancers. Accordingly, the review is divided into two parts, i.e., the effect of CDs as active drugs and as enhancers in antimicrobials, antivirals, cardiovascular diseases, cancer, neuroprotective agents, and antioxidants.

Cyclodextrins in Skin Formulations and Transdermal Delivery

: This mini review aims to describe the main physicochemical properties and characteristics of cyclodextrin derivatives (CDs) having been used in various skin-related formulations over the last nearly 50 years. Due to many misunderstandings and inconsistent data on the Internet, the basic properties of CDs, water content, solubility properties, and maximum complexing capabilities are summarized. CDs are grouped by their solubility properties and briefly described by chemical synthesis to reveal the potential contaminants. Soluble and insoluble CD-based polymers are also discussed.

Ladder chain Cd-based polymer as a highly effective adsorbent for removal of Congo red

Developing of high effective and fast-rate adsorbent materials has been recently attracted intensive attentions all over the world due to organic dye polluted water treatment. However, few studies have been reported on the ultrahigh-capacity and fast-rate removal of Congo red. In this work, a new stable Cd-based coordination polymer exhibits excellent adsorption performance towards Congo Red. This ladder chain [Cd4(H2L)4(H2O)8(NDS)]n·3n(NDS) (I) (H2L = N1,N2-bis(pyridin-3-ylmethyl) ethane-1,2-diamine, 1,5-H2NDS = 1,5-naphthalene disulfonic acid) has been successfully synthesized by the hydrothermal reaction. At room temperature, the experimental adsorption capacity of coordination polymer (I) towards Congo red can reach up to 16,880 mg g−1 in 20 min (pH = 2.0–3.2), and its higher capacity and faster rate are all better than those in reported inorganic and metal-organic frameworks absorbents. The adsorption process is spontaneous and endothermic reaction, and fits well with the second-order kinetics, Langmuir and Scatchard isotherm adsorption models. The excellent adsorption performance of (I) towards Congo red is related to the strong electrostatic, various hydrogen bonding and π-π stacking interactions under acidic conditions.

Nine Mn(II), Zn(II) and Cd(II) mixed-ligand coordination networks with rigid dicarboxylate and pyridine-n-aldoxime ligands: Impact of the second ligand in the structures’ dimensionality and solvent capacity

Using the ‘dicarboxylic acid/oxime blend approach’ nine coordination polymers, [M(fum)(2-pyao)2]n, M=Mn(II), Zn(II), Cd(II) (1–3), [Mn(1,3-bdc)(2-pyao)2]n (4), [Cd(1,3-bdc)(2-pyao)]n (5), {[Cd(1,3-bdc)(4-pyao)(H2O)2]·dmf·H2O}n (6), {[Cd(1,4-bdc)(4-pyao)2(H2O)]·dmf}n (7) and {[M(1,4-bdc)(4-pyao)2]·dmf}n, M=Zn(II), Cd(II) (8, 9) (where 2-pyao=pyridine-2-aldoxime, 4-pyao=pyridine-4-aldoxime, fumH2=fumaric acid, 1,3-bdcH2=1,3-benzenedicarboxylic acid and 1,4-bdcH2=1,4-benzenedicarboxylic acid) have been prepared, and their crystal structures have been determined by single crystal X-ray diffraction. Compounds 1–4, 6 and 7 represent 1D coordination polymers, while compounds 5, 8 and 9 represent laminar 2D structures. In compounds 1–4 two terminal 2-pyao ligands take the common bidentate chelating coordination mode that results in five-membered chelate rings revealing a “butterfly wings” shape. The oxime’s hydroxyl group participates in an intramolecular OH⋯O hydrogen bond with the dicarboxylic oxygen atoms, which are uncoordinated to the metal center, thus fortifying the metals’ coordination cores. In 6–9 the pillared monodentate 4-pyao ligands, due to their bulkiness and terminal hydroxyl-groups, essentially increase the solvent accessible areas, and the hydrophilic regions in the structures facilitate the accommodation of polar solvents (dmf and water) and their retention in the crystal lattice via hydrogen bonding with OH-ligands (4-pyao, water). All the compounds were tested as luminescent materials, with the Cd-based polymers 3, 5 and 6 revealing the highest emission response.

Pseudopolyrotaxane Formation in the Synthesis of Cyclodextrin Polymers: Effects on Drug Delivery, Mechanics, and Cell Compatibility.

Numerous groups have reported the use of cyclodextrin (CD)-based polymers for drug delivery applications due to their capacity to form inclusions with small molecule drugs, delaying the rate of drug release beyond that of diffusion alone (termed "affinity-based" drug delivery). Herein we demonstrate synthesis and characterization of a new family of CD-based polymers, some as pseudopolyrotaxanes, generated under mild (aqueous, room temperature) conditions. The formation of these new affinity polymers results in broad mechanical properties. Three diglycidylether cross-linkers which vary in length from 0 to 10 ethylene glycol units were examined. Pseudopolyrotaxane formation was found only with the highest-length cross-linker, noted first by a sharp change in both material properties and then confirmed by chemical signature. Materials were thoroughly evaluated by NMR, DSC, DMA, TGA, XRD, and FTIR. Cross-linker choice was also tested for impact on drug loading and delivery capacity, using antibiotics as model drugs. Chemically similar polymers without showing affinity rapidly saturated in loading experiments, while affinity materials showing high capacity for drug loading, even beyond the solubility limit of the drugs. When using the polymers with these new cross-linkers, affinity-based drug delivery is maintained: the materials are capable of antibiotic delivery, and clearance of Staphylococcus aureus, at least an order of magnitude better than diffusion-only control polymers. In cell compatibility studies, CD-based polymers were shown to have low overt cell toxicity and even resisted cell adhesion, presumably due to their highly hydrated state.

Electrospun Fibers of Cyclodextrins and Poly(cyclodextrins).

Cyclodextrins (CDs) can endow electrospun fibers with outstanding performance characteristics that rely on their ability to form inclusion complexes. The inclusion complexes can be blended with electrospinnable polymers or used themselves as main components of electrospun nanofibers. In general, the presence of CDs promotes drug release in aqueous media, but they may also play other roles such as protection of the drug against adverse agents during and after electrospinning, and retention of volatile fragrances or therapeutic agents to be slowly released to the environment. Moreover, fibers prepared with empty CDs appear particularly suitable for affinity separation. The interest for CD-containing nanofibers is exponentially increasing as the scope of applications is widening. The aim of this review is to provide an overview of the state-of-the-art on CD-containing electrospun mats. The information has been classified into three main sections: (i) fibers of mixtures of CDs and polymers, including polypseudorotaxanes and post-functionalization; (ii) fibers of polymer-free CDs; and (iii) fibers of CD-based polymers (namely, polycyclodextrins). Processing conditions and applications are analyzed, including possibilities of development of stimuli-responsive fibers.

Preparation of Tris(2‐aminoethyl)amine‐Cross‐Linked Cyclodextrin‐Based Porous Nanospheres and Their Application as Drug Delivery Systems

AbstractCyclodextrins (CDs) show functionality, biocompatibility, and host‐guest inclusion capacity with a variety of molecules. These unique properties offer great potential for the exploitation of CDs as drug delivery systems. An easy, green, and effective synthetic approach was described to develop CD‐based porous nanospheres (CDPNSs) with a size distribution from 100 to 400 nm. A new cross‐linker tris(2‐aminoethyl)amine was used to cross‐link modified β‐CD at room temperature. The resulting CD‐based polymers (CDPs) were reshaped from a random morphology into a spherical shape during a dialysis process, and CDPNSs were obtained. The morphologies of CDPs and CDPNSs were observed with scanning electron microscopy. The average diameter and the size distribution of CDPNSs were determined by dynamic light scattering. The structures of the resulting products were characterized by using Fourier transform infrared spectroscopy, 1H NMR spectroscopy, solid‐state 13C CP/MAS NMR spectroscopy, and X‐ray diffraction. Furthermore, a study was conducted on drug loading and in vitro release behavior of CDPNSs, which was monitored by ultraviolet spectroscopy. The prepared CDPNSs show the potential as drug delivery systems.

CD-Based Microfluidic Device for Automated Immobilization and Microinjection of Biological Cells

The paper presents the design concept of automatic CD-based polymer microfluidic device for single cell immobilization applicable for use in robotic system for microinjection of substances into cells. The device is also provided for use as a standalone system for cell immobilization for their research and to carry out various micro- manipulations with cells. Key role in the functioning of the device plays a CD-based polymer substrate, on whose surface is specifically located microstructure in the form of micro-grooves for immobilization of cells. At the bottom of the micro-grooves are made suction holes. Immobilization of cells is achieved through the subatmospheric pressure provided by micro pump, connected to the micro-grooves by suction holes. The structure of the substrate is provided to be produced by injection molding. A possibility of using CD-based technology in injection moulding of the micro-patterned substrate is discussed. An approach to study the substrate through computer simulation by the finite element method is presented. In order to achieve an appropriate location and size of microstructure on the polymer substrate, impact of geometrical parameters of the gating system and the size, dimensions and location of the microstructure of the substrate on the mold filling is investigated. By means of iterative steps in the frame of the simulation codes, a series of values of the microstructure parameters are obtained and relevant versions of the substrate design with the deployment of cell-grooves are achieved. The present design of the CD-based substrate and the approach for investigation of substrate can find applications in the construction of CD-based devices for immobilization of biological cells for research or micro-injection of cells. Keywords: CD-based microfluidic device, CD microfluidic chips, cell, computer simulation, micro-patterned polymer substrate, cell immobilization, IVD, Cell Microinjection, CD-based polymer, microinjection

Solid Phase Host−Guest Properties of Cyclodextrins and Calixarenes Covalently Attached to a Polysilsesquioxane Matrix

A new family of silicon-based polymers has been prepared with covalently bound hosts. The polymer is a polysilsesquioxane formed by the sol−gel process, and the hosts are cyclodextrins (CD) or calixarenes (CX). The organic and silicon structures are supported by solid-state NMR spectroscopy. The nanoporous polymer is relatively stable to a variety of aqueous conditions. It is a water-insoluble material, which binds with and extracts both organic compounds and metal cations from water. The polymer containing the guests is then removed by filtration. The objective achieved can be either removal of impurities from water or recovery of materials dissolved in water. The CD-based polymer may be renewed by treatment with ethanol. Its binding ability is equal or superior to that of other available materials such as activated charcoal.