ABSTRACT
Cyclodextrins, commonly used as excipients in antifungal formulations to improve the physicochemical properties and availability of the host molecules, have not been systematically studied for their effects and bioactivity without a complex active substance. This paper evaluates the effects of various cyclodextrins on the physiology of the test organism Candida boidinii. The research examines their impact on yeast growth, viability, biofilm formation and morphological changes. Native ACD, BCD, randomly methylated α- and ß-CD and quaternary ammonium α-CD and ß-CD were investigated in the 0.5-12.5 mM concentration range in both static and dynamic systems. The study revealed that certain cyclodextrins exhibited notable antifungal effects (up to ~69%) in dynamic systems; however, the biofilm formation was enhanced in static systems. The magnitude of these effects was influenced by several variables, including the size of the internal cavity, the concentration and structure of the cyclodextrins, and the contact time. Furthermore, the study found that CDs exhibited distinct effects in both static and dynamic systems, potentially related to their tendency to form aggregates. The findings suggest that cyclodextrins may have the potential to act as antifungal agents or growth promoters, depending on their structure and surrounding environments.
Subject(s)
Antifungal Agents , Biofilms , Candida , Cyclodextrins , Candida/drug effects , Cyclodextrins/chemistry , Cyclodextrins/pharmacology , Antifungal Agents/pharmacology , Antifungal Agents/chemistry , Biofilms/drug effects , Biofilms/growth & development , Microbial Sensitivity TestsABSTRACT
This study evaluates the antiproliferative potential of flavanones, chromanones and their spiro-1-pyrazoline derivatives as well as their inclusion complexes. The main goal was to determine the biological basis of molecular pro-apoptotic activities and the participation of reactive oxygen species (ROS) in shaping the cytotoxic properties of the tested conjugates. For this purpose, changes in mitochondrial potential and the necrotic/apoptotic cell fraction were analyzed. Testing with specific fluorescent probes found that ROS generation had a significant contribution to the biological anticancer activity of complexes of flavanone analogues. TT (thrombin time), PT (prothrombin time) and APTT (activated partial tromboplastin time) were used to evaluate the influence of the compounds on the extrinsic and intrinsic coagulation pathway. Hemolysis assays and microscopy studies were conducted to determine the effect of the compounds on RBCs.
Subject(s)
Antineoplastic Agents , Apoptosis , Cyclodextrins , Flavanones , Reactive Oxygen Species , Humans , Flavanones/pharmacology , Flavanones/chemistry , Apoptosis/drug effects , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Reactive Oxygen Species/metabolism , Cyclodextrins/chemistry , Cyclodextrins/pharmacology , Cell Line, Tumor , Hemolysis/drug effects , Membrane Potential, Mitochondrial/drug effects , Cell Proliferation/drug effectsABSTRACT
Water-soluble polymers of cyclodextrins (CyD) can be easily obtained in alkaline media following polycondensation of the naturally occurring monomers in the presence of a crosslinking agent. They can be further modified to customize specifically functionalized architectures. Compared to other macromolecules natural and not, the CyD polymers are endowed with a unique feature, the cone-shaped cavities where they can host guests of various nature. This element has sollicited interest in this class of molecules for a wide range of applications including the biomedical field, in particular drug delivery. The CyD polymers display excellent behavior in terms of water solubility and solubilizing power towards drugs and therapeutic agents that are incompatible with biological fluids. Moreover, they can load more than one type of therapeutic agent in a single system thus allowing to implement combination therapy. In spite of some very promising results as delivery systems, their potentialities remain limited by some intrinsic hurdles. Herein, we comment on their limits mainly related to the production process and the possible solutions to overcome them, giving an outlook on their assets for innovation in disease treatment.
Subject(s)
Cyclodextrins , Polymers , Solubility , Water , Cyclodextrins/chemistry , Water/chemistry , Polymers/chemistry , Humans , Drug Delivery Systems , Drug Carriers/chemistry , CelluloseABSTRACT
Purpose: Conventional oral formulations for inflammatory bowel disease (IBD) treatment are less than satisfactory, due to the poor controllability of drug release and lack of specificity to the inflammation sites in the gastrointestinal (GI) tract. To overcome these limitations, we developed a multiple carbohydrate-based nanosystem with pH/ROS dual responsibility and charge-mediated targeting ability for IBD-specific drug delivery. Methods: In view of the overproduction of ROS and overexpression of cationic proteins in the inflammatory colon, the designed nanosystem was composed of oxidation-sensitive cyclodextrin (OX-CD), chitosan (CS) and pectin (AHP). OX-CD was utilized to load dexamethasone (DM) by the solvent evaporation method. CS and AHP with opposite charges were sequentially coated onto OX-CD to generate the nanosystems by the electrostatic self-assembly method. The physicochemical properties, stability, dual-sensitive drug release behavior, cytotoxicity, cellular uptake and anti-inflammatory activity were investigated in vitro. In vivo bio-distribution and therapeutic efficacy of the nanosystem were further evaluated in the ulcerative colitis (UC) mice. Results: The obtained AHP/CS/OX-CD-DM nanosystem (ACOC-DM) could maintain stability under the GI pH environments, and release drug in the inflammatory colon with pH/ROS sensitivity. Dual polysaccharide-coated ACOC-DM exhibited higher cellular uptake and anti-inflammatory efficacy in macrophages than single polysaccharide-coated CS/OX-CD-DM nanosystem (COC-DM). Orally administrated ACOC-DM could enhance inflammation targeting ability and therapeutic efficacy of DM in the UC mice. Conclusion: This carbohydrate-based nanosystem with pH/ROS dual sensitivity and inflammation targeting capacity may serve as a safe and versatile nanoplatform for IBD therapy.
Subject(s)
Anti-Inflammatory Agents , Chitosan , Colitis, Ulcerative , Dexamethasone , Pectins , Animals , Colitis, Ulcerative/drug therapy , Mice , Chitosan/chemistry , Dexamethasone/chemistry , Dexamethasone/administration & dosage , Dexamethasone/pharmacokinetics , Dexamethasone/pharmacology , Pectins/chemistry , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/pharmacokinetics , Cyclodextrins/chemistry , Cyclodextrins/pharmacology , Drug Delivery Systems/methods , Drug Liberation , RAW 264.7 Cells , Hydrogen-Ion Concentration , Humans , Reactive Oxygen Species/metabolism , Colon/drug effects , Colon/metabolism , Drug Carriers/chemistry , Male , Nanoparticles/chemistryABSTRACT
Quercetin, recognized for its antioxidant, anti-inflammatory, and antibacterial properties, faces limited biomedical application due to its low solubility. Cotton, a preferred wound dressing material over synthetic ones, lacks inherent antibacterial and wound-healing attributes and can benefit from quercetin features. This study explores the potential of overcoming these challenges through the inclusion complexation of quercetin with cyclodextrins (CDs) and the development of a nanofibrous coating on a cotton nonwoven textile. Hydroxypropyl-beta-cyclodextrin (HP-ß-CD) and hydroxypropyl-gamma-cyclodextrin (HP-γ-CD) formed inclusion complexes of quercetin, with chitosan added to enhance antibacterial properties. Phase solubility results showed that inclusion complexation can enhance quercetin solubility up to 20 times, with HP-γ-CD forming a more stable inclusion complexation compared with HP-ß-CD. Electrospinning of the nanofibers from HP-ß-CD/Quercetin and HP-γ-CD/Quercetin aqueous solutions without the use of a polymeric matrix yielded a uniform, smooth fiber morphology. The structural and thermal analyses of the HP-ß-CD/Quercetin and HP-γ-CD/Quercetin nanofibers confirmed the presence of inclusion complexes between quercetin and each of the CDs (HP-ß-CD and HP-γ-CD). Moreover, HP-ß-CD/Quercetin and HP-γ-CD/Quercetin nanofibers showed a near-complete loading efficiency of quercetin and followed a fast-releasing profile of quercetin. Both HP-ß-CD/Quercetin and HP-γ-CD/Quercetin nanofibers showed significantly higher antioxidant activity compared to pristine quercetin. The HP-ß-CD/Quercetin and HP-γ-CD/Quercetin nanofibers also showed antibacterial activity, and with the addition of chitosan in the HP-γ-CD/Quercetin system, the Chitosan/HP-γ-CD/Quercetin nanofibers completely eliminated the investigated bacteria species. The nanofibers were nontoxic and well-tolerated by cells, and exploiting the quercetin and chitosan anti-inflammatory activities resulted in the downregulation of IL-6 and NO secretion in both immune as well as regenerative cells. Overall, CD inclusion complexation markedly enhances quercetin solubility, resulting in a biofunctional antioxidant, antibacterial, and anti-inflammatory wound dressing through a nanofibrous coating on cotton textiles.
Subject(s)
Anti-Bacterial Agents , Anti-Inflammatory Agents , Antioxidants , Bandages , Chitosan , Cyclodextrins , Materials Testing , Nanofibers , Quercetin , Quercetin/pharmacology , Quercetin/chemistry , Antioxidants/pharmacology , Antioxidants/chemistry , Nanofibers/chemistry , Chitosan/chemistry , Chitosan/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Cyclodextrins/chemistry , Cyclodextrins/pharmacology , Particle Size , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Microbial Sensitivity Tests , Cotton Fiber , Wound Healing/drug effects , Humans , Picrates/antagonists & inhibitors , Cell Survival/drug effects , Biphenyl CompoundsABSTRACT
BACKGROUND: Vitamin E ( -tocopherol) and cholesterol are crucial components in cellular protection and physiological processes. Their uses in biological media face challenges due to their poor solubility and stability. OBJECTIVE: The study investigated the complex interactions of these bioactive compounds in various encapsulation systems of cyclodextrin and liposome, as well as dispersion in PEG-6000, in an attempt to improve the viability, motility, and preservation of ovine sperm cells. MATERIALS AND METHODS: The work explored the in vitro dissolution kinetics of vitamin E (d-tocopherol) and cholesterol using semi-empirical models. RESULTS: The release profiles of VitE and Chl varied considerably, depending on the specific carrier systems. For liposome-loaded VitE and Chl, the Korsmeyer-Peppas model gave the best fit; for CD/VitE and CD/Chl, the Higuchi model provided the best fit, whereas for PEG-6000 dispersions (VitE and Chl) both the Higuchi and Korsmeyer-Peppas models demonstrated the excellent fit. All systems indicated a Fickian diffusion mechanism dictated by the concentration gradient. The delivery of VitE and Chl with CD, liposome and PEG dispersion significantly increased sperm mobility and motility. The effect on the VCL parameter was the greatest by liposome-loaded VitE and Chl, followed by CD encapsulation and PEG-6000 dispersion. CONCLUSION: The dynamics of vitamin E and cholesterol within innovative delivery systems offers valuable insights into the development of advanced solutions in reproductive health, particularly on improving the viability, motility of refrigerated ovine sperm cells. Doi.org/10.54680/fr24510110712.
Subject(s)
Cholesterol , Liposomes , Semen Preservation , Sperm Motility , Spermatozoa , Vitamin E , Animals , Male , Vitamin E/chemistry , Cholesterol/chemistry , Cholesterol/metabolism , Sheep , Semen Preservation/methods , Semen Preservation/veterinary , Spermatozoa/drug effects , Spermatozoa/physiology , Sperm Motility/drug effects , Liposomes/chemistry , Cyclodextrins/chemistry , Polyethylene Glycols/chemistry , Solubility , Cell Survival/drug effects , Cryopreservation/methodsABSTRACT
Cilostazol is a phosphodiesterase III inhibitor characterized by poor solubility. This limitation can be overcome by using a drug carrier capable of delivering the drug to the target site. Cyclodextrins are essential as drug carriers because of their outstanding complexation abilities and their capacity to improve drug bioavailability. This study comprises two stages: The first involves verifying different cyclodextrins and their complexation abilities towards cilostazol. This was accomplished using molecular docking simulations (MDS) and density functional theory (DFT). Both techniques indicate that the largest Sulfobutyl Ether-ß-Cyclodextrin forms the most stable complex with cilostazol. Additionally, other important parameters of the complex are described, including binding sites, dominant interactions, and thermodynamic parameters such as complexation enthalpy, Gibbs free energy, and Gibbs free energy of solvation. The second stage involves a binding study between cilostazol and Phosphodiesterse3 (PDE3). This study was conducted using molecular docking simulations, and the most important energetic parameters are detailed. This is the first such report, and we believe that the results of our predictions will pave the way for future drug development efforts using cyclodextrin-cilostazol complexes as potential therapeutics.
Subject(s)
Cilostazol , Cyclodextrins , Molecular Docking Simulation , Phosphodiesterase 3 Inhibitors , Thermodynamics , Cilostazol/chemistry , Phosphodiesterase 3 Inhibitors/chemistry , Phosphodiesterase 3 Inhibitors/pharmacology , Cyclodextrins/chemistry , Binding Sites , Cyclic Nucleotide Phosphodiesterases, Type 3/chemistry , Cyclic Nucleotide Phosphodiesterases, Type 3/metabolism , Protein Binding , HumansABSTRACT
Efficient delivery of therapeutic agents to the lesion site or specific cells is an important way to achieve "toxicity reduction and efficacy enhancement". Macrocycles have always provided many novel ideas for drug or gene loading and delivery processes. Specifically, macrocycles represented by crown ethers, cyclodextrins, cucurbit[n]urils, calix[n]arenes, and pillar[n]arenes have unique properties, which are different cavity structures, good biocompatibility, and good stability. Benefited from these diverse properties, a variety of supramolecular drug delivery systems can be designed and constructed to effectively improve the physical and chemical properties of guest molecules as needed. This review provides an outlook on the current application status and main limitations of macrocycles in supramolecular drug delivery systems.
Subject(s)
Drug Delivery Systems , Macrocyclic Compounds , Macrocyclic Compounds/chemistry , Humans , Drug Carriers/chemistry , Cyclodextrins/chemistry , Calixarenes/chemistry , Macromolecular Substances/chemistry , Crown Ethers/chemistryABSTRACT
Cyclodextrin, a potent anti-tumor medication utilized predominantly in ovarian and breast cancer treatments, encounters significant challenges such as poor solubility, potential side effects, and resistance from tumor cells. Combining cyclodextrin with biocompatible substrates offers a promising strategy to address these obstacles. Understanding the atomic structure and physicochemical properties of cyclodextrin and its derivatives is essential for enhancing drug solubility, modification, targeted delivery, and controlled release. In this study, we investigate the topological indices of cyclodextrin using algebraic polynomials, specifically the degree-based M-polynomial and neighbor degree-based M-polynomial. By computing degree-based and neighbor degree-based topological indices, we aim to elucidate the structural characteristics of cyclodextrin and provide insights into its physicochemical behavior. The computed indices serve as predictive tools for assessing the health benefits and therapeutic efficacy of cyclodextrin-based formulations. In addition, we examined that the computed indices showed a significant relationship with the physicochemical characteristics of antiviral drugs. Graphical representations of the computed results further facilitate the visualization and interpretation of cyclodextrin's molecular structure, aiding researchers in designing novel drug delivery systems with improved pharmacological properties.
Subject(s)
Cyclodextrins , Cyclodextrins/chemistry , Solubility , Humans , Chemical Phenomena , Drug Delivery Systems , Antiviral Agents/chemistry , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacologyABSTRACT
Aiming to improve the retrieval rate of retrievable vena cava filters (RVCF) and extend its dwelling time in vivo, a novel hydrogel coating loaded with 10 mg/mL heparin and 30 mg/mL cyclodextrin/paclitaxel (PTX) inclusion complex (IC) was prepared. The drug-release behavior in the phosphate buffer solution demonstrated both heparin and PTX could be sustainably released over approximately two weeks. Furthermore, it was shown that the hydrogel-coated RVCF (HRVCF) with 10 mg/mL heparin and 30 mg/mL PTX IC effectively extended the blood clotting time to above the detection limit and inhibited EA.hy926 and CCC-SMC-1 cells' proliferation in vitro compared to the commercially available bare RVCF. Both the HRVCF and the bare RVCF were implanted into the vena cava of sheep and retrieved at at 2nd and 4th week after implantation, revealing that the HRVCF had a significantly higher retrieval rate of 67 % than the bare RVCF (0 %) at 4th week. Comprehensive analyses, including histological, immunohistological, and immunofluorescent assessments of the explanted veins demonstrated the HRVCF exhibited anti-hyperplasia and anticoagulation properties in vivo, attributable to the hydrogel coating, thereby improving the retrieval rate in sheep. Consequently, the as-prepared HRVCF shows promising potential for clinical application to enhance the retrieval rates of RVCFs.
Subject(s)
Cyclodextrins , Heparin , Hydrogels , Paclitaxel , Vena Cava Filters , Cyclodextrins/chemistry , Cyclodextrins/pharmacology , Paclitaxel/pharmacology , Paclitaxel/chemistry , Heparin/chemistry , Heparin/pharmacology , Animals , Hydrogels/chemistry , Hydrogels/pharmacology , Humans , Sheep , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Blood Coagulation/drug effects , Cell Proliferation/drug effects , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Drug LiberationABSTRACT
This work aimed to explore an alternative to the use of antibiotics for prevention and treatment of wounds infection caused by two common bacterial pathogens Staphylococcus aureus and Pseudomonas aeruginosa. For this purpose, three different essential oil components (EOCs), namely carvacrol, citronellol and cinnamic acid, were loaded into electrospun fibers of poly-ε-caprolactone (PCL) aided by alpha-cyclodextrin (αCD) and hydroxypropyl-ß-cyclodextrin (HPßCD). Electrospun-fibers prepared with each EOC and their mixtures were screened for antimicrobial capability and characterized regarding morphological, mechanical, thermal, surface polarity, antibiofilm and antioxidant properties. αCD formed poly(pseudo)rotaxanes with PCL and weakly interacted with EOCs, while HPßCD facilitated EOC encapsulation and formation of homogeneous fibers (500-1000 nm diameter) without beads. PCL/HPßCD fibers with high concentration of EOCs (mainly carvacrol and cinnamic acid) showed strong antibiofilm (>3 log CFU reduction) and antioxidant activity (10-50% DPPH scavenging effects). Different performances were recorded for the EOCs and their mixtures; cinnamic acid migrated to fiber surface and was released faster. Fibers biocompatibility was verified using hemolysis tests and in ovo tissue integration and angiogenesis assays. Overall, HPßCD facilitates complete release of EOCs from the fibers to the aqueous medium, being an environment-friendly and cost-effective strategy for the treatment of infected wounds.
Subject(s)
Acyclic Monoterpenes , Antioxidants , Cinnamates , Cymenes , Monoterpenes , Wound Healing , Wound Healing/drug effects , Cymenes/pharmacology , Cymenes/chemistry , Cinnamates/chemistry , Cinnamates/pharmacology , Acyclic Monoterpenes/pharmacology , Acyclic Monoterpenes/chemistry , Antioxidants/pharmacology , Antioxidants/chemistry , Monoterpenes/pharmacology , Monoterpenes/chemistry , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemistry , Staphylococcus aureus/drug effects , Cyclodextrins/chemistry , Cyclodextrins/pharmacology , Biofilms/drug effects , Nanofibers/chemistry , Microbial Sensitivity Tests , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Polyesters/chemistry , Oils, Volatile/pharmacology , Oils, Volatile/chemistry , Pseudomonas aeruginosa/drug effectsABSTRACT
This study addresses the challenge of accurately identifying stereoisomers in cheminformatics, which originates from our objective to apply machine learning to predict the association constant between cyclodextrin and a guest. Identifying stereoisomers is indeed crucial for machine learning applications. Current tools offer various molecular descriptors, including their textual representation as Isomeric SMILES that can distinguish stereoisomers. However, such representation is text-based and does not have a fixed size, so a conversion is needed to make it usable to machine learning approaches. Word embedding techniques can be used to solve this problem. Mol2vec, a word embedding approach for molecules, offers such a conversion. Unfortunately, it cannot distinguish between stereoisomers due to its inability to capture the spatial configuration of molecular structures. This study proposes several approaches that use word embedding techniques to handle molecular discrimination using stereochemical information on molecules or considering Isomeric SMILES notation as a text in Natural Language Processing. Our aim is to generate a distinct vector for each unique molecule, correctly identifying stereoisomer information in cheminformatics. The proposed approaches are then compared to our original machine learning task: predicting the association constant between cyclodextrin and a guest molecule.
Subject(s)
Machine Learning , Stereoisomerism , Cheminformatics/methods , Cyclodextrins/chemistry , Natural Language ProcessingABSTRACT
Slide-ring hydrogels containing polyrotaxane structures have been widely developed, but current methods are more complex, in which modified cyclodextrins, capped polyrotaxanes, and multistep reactions are often needed. Here, a simple one-pot method dissolving the pseudopolyrotaxane (pPRX) in a mixture of acrylamide and boric acid to form a slide-ring hydrogel by UV light is used to construct a tough, puncture-resistant antibacterial polyrotaxane hydrogel. As a new dynamic ring cross-linking agent, boric acid effectively improves the mechanical properties of the hydrogel and involves the hydrogel with fracture toughness. The polyrotaxane hydrogel can withstand 1 MPa compression stress and maintain the morphology integrity, showing 197.5 mJ puncture energy under a sharp steel needle puncture. Meanwhile, its significant antibacterial properties endow the hydrogel with potential applications in the biomedical field.
Subject(s)
Anti-Bacterial Agents , Cyclodextrins , Escherichia coli , Hydrogels , Poloxamer , Rotaxanes , Rotaxanes/chemistry , Rotaxanes/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/chemical synthesis , Hydrogels/chemistry , Hydrogels/pharmacology , Hydrogels/chemical synthesis , Poloxamer/chemistry , Escherichia coli/drug effects , Cyclodextrins/chemistry , Boric Acids/chemistry , Boric Acids/pharmacology , Microbial Sensitivity Tests , Staphylococcus aureus/drug effectsABSTRACT
Quorum sensing (QS) allows bacteria to coordinate their activities by producing and detecting low-molecular-weight signal molecules based on population density, thereby controlling the infectivity of bacteria through various virulence factors. Quorum-sensing inhibition is a promising approach to tackle bacterial communication. Cyclodextrins (CDs) are a class of cyclic oligosaccharides that reversibly encapsulate the acyl chain of the signal molecules, thereby preventing their binding to receptors and interrupting bacterial communication. This results in the inhibition of the expression of various properties, including different virulence factors. To examine the potential quorum-quenching (QQ) ability of newly prepared cyclodextrin derivatives, we conducted short-term tests using Aliivibrio fischeri, a heterotrophic marine bacterium capable of bioluminescence controlled by quorum sensing. α- and ß-cyclodextrins monosubstituted with alkylthio moieties and further derivatized with quaternary ammonium groups were used as the test agents. The effect of these cyclodextrins on the quorum-sensing system of A. fischeri was investigated by adding them to an exponential growth phase of the culture and then measuring bioluminescence intensity, population growth, and cell viability. Our results demonstrate that the tested cyclodextrins have an inhibitory effect on the quorum-sensing system of A. fischeri. The inhibitory effect varies based on the length of the alkyl chain, with alkylthio substitution enhancing it and the presence of quaternary ammonium groups decreasing it. Our findings suggest that cyclodextrins can be a promising therapeutic agent for the treatment of bacterial infections.
Subject(s)
Aliivibrio fischeri , Cyclodextrins , Quorum Sensing , Aliivibrio fischeri/drug effects , Quorum Sensing/drug effects , Cyclodextrins/pharmacology , Cyclodextrins/chemistry , Luminescent Measurements/methods , LuminescenceABSTRACT
BACKGROUND: Cyclodextrins are a well-established system which form inclusion complexes with many guest molecules. This property can be easily exploited to develop drug delivery systems. Additionally, carbon dots (CD) are a low-toxic photoluminescent product which have been used as luminescent tags. The combination of cyclodextrins and carbon dots allows obtaining a new nanoplatform, a biocompatible material, with both capabilities, increasing as well the internalization by the cells of the CD, induced by the cyclodextrins. RESULTS: In the present work, we have modified the surface of carbon dots obtained from citric acid and glutathione with ß and γ cyclodextrins. After a morphological and spectroscopic characterization, we concluded that the luminescence quantum yield and absorption molar coefficient of the derivatized and unmodified carbon dots was the same. These findings, together with the spectroscopic detection of active cyclodextrins, those bond to the CD able to interact with a guest molecule, allowed determination of the ratios: cyclodextrins/CD, active cyclodextrins/CD and an estimation of the CD molecular mass. Furthermore, the biocompatibility of the new materials was evaluated through cytotoxicity and cell-penetrance assays revealing that the materials were non cytotoxic up to 0.1 mg/mL. Moreover, the biocompatible developed nanoplatform penetrates in the cells maintaining the material's intrinsic fluorescence, thus constituting an adequate photoluminescent-tag with high-contrast for in vitro cell imaging. SIGNIFICANCE: This work provides a new and easy method to combine cyclodextrins and carbon dots into a biocompatible material which can be used as nanoplatform both as drug delivery system and as photoluminescent tag in cell imaging. Likewise, this paper shows how to characterize the number of cyclodextrins and active cyclodextrins per CD, having an average stoichiometric relation of 1:1 for guest molecule - CD. Additionally, the minimum molecular mass of the unmodified CD was indirectly obtained, yielding about 1.6-1.9 kDa.
Subject(s)
Biocompatible Materials , Carbon , Cyclodextrins , Quantum Dots , Surface Properties , Carbon/chemistry , Quantum Dots/chemistry , Quantum Dots/toxicity , Cyclodextrins/chemistry , Humans , Biocompatible Materials/chemistry , Cell Survival/drug effects , Drug Delivery Systems , Optical ImagingABSTRACT
Starch is extensively used across various fields due to its renewable properties and cost-effectiveness. Nonetheless, the high viscosity that arises from gelatinization poses challenges in the industrial usage of starch at high concentrations. Thus, it's crucial to explore techniques to lower the viscosity during gelatinization. In this study, large-ring cyclodextrins (LR-CDs) were synthesized from potato starch (PS) by using 4-α-glucanotransferase and then added to PS to alleviate the increased viscosity during gelatinization. The results from rapid viscosity analyzer (RVA) demonstrated that the inclusion of 5 % (w/w) LR-CDs markedly reduced the peak viscosity (PV) and final viscosity (FV) of PS by 49.85 % and 28.17 %. In addition, there was a quantitative relationship between PV and LR-CDs. The equation was fitted as y = 2530.73×e-x/2.48+1832.79, which provided a basis for the regulation of PS viscosity. The mechanism of LR-CDs reducing the viscosity of PS was also studied. The results showed that the addition of LR-CDs inhibited the gelatinization of PS by enhancing orderliness and limiting water absorption, resulting in a decrease in viscosity. This study provides a novel method for reducing the viscosity of starch, which is helpful for increasing its concentration and reducing energy consumption in industrial applications.
Subject(s)
Cyclodextrins , Solanum tuberosum , Starch , Solanum tuberosum/chemistry , Viscosity , Starch/chemistry , Cyclodextrins/chemistryABSTRACT
Cyclodextrins (CDs) are unique cyclic compounds that can form inclusion complexes via host-guest complexation with a wide range of molecules, thereby altering their physicochemical properties. These molecules offer the formation of inclusion complexes without the formation of covalent bonds, making them suitable for a variety of applications in pharmaceutical and biomedical fields. Due to their supramolecular host-guest properties, CDs are being utilized in the fabrication of biomaterials, metal-organic frameworks, and nano-drug carriers. Additionally, CDs in combination with biomolecules are biocompatible and can deliver nano to macromolecules at the site of drug actions. However, the availability of free hydroxyl groups and a simple crosslinking process for supramolecular fabrication show immense opportunities for researchers in the field of tissue engineering and biomedical applications. In this review article, we have covered the historical development, various types of chemical frameworks, unique chemical and physical properties, and important applications of CDs in drug delivery and biomedical sciences.
Subject(s)
Cyclodextrins , Drug Carriers , Drug Delivery Systems , Cyclodextrins/chemistry , Humans , Drug Carriers/chemistry , Animals , Biocompatible Materials/chemistry , Tissue Engineering/methodsABSTRACT
There is an urgent need to develop safer and more effective modalities for the treatment of numerous pathologies due to the increasing rates of drug resistance, undesired side effects, poor clinical outcomes, etc. Over the past decades, cyclodextrins (CDs) have gathered great attention as potential drug carriers due to their ability to enhance their bioactivities and properties. Likewise, selenium (Se) and tellurium (Te) have been extensively studied during the last decades due to their possible therapeutical applications. Although there is limited research on the relationship between Se and Te and CDs, herein, we highlight different representative examples of the advances related to this topic as well as give our view on the future directions of this emerging area of research. This review encompasses three different aspects of this relationship: (1) modification of the structure of the different CDs; (2) formation of host-guest interaction complexes of naïve CDs with Se and Te derivatives in order to overcome specific limitations of the latter; and (3) the use of CDs as catalysts to achieve novel Se and Te compounds.
Subject(s)
Cyclodextrins , Selenium , Tellurium , Tellurium/chemistry , Cyclodextrins/chemistry , Cyclodextrins/pharmacology , Selenium/chemistry , Humans , Drug Carriers/chemistry , AnimalsABSTRACT
Ibuprofen is a well-known and broadly used, nonsteroidal anti-inflammatory and painkiller medicine. Ibuprofen is a chiral compound, and its two isomers have different biological effects, therefore, their chiral separation is necessary. Ibuprofen and its derivatives were used as model compounds to establish transportable structure chiral selectivity relationships. Chiral selectors were permethylated α-, ß-, and γ-cyclodextrins containing gas chromatographic stationary phases. The chiral selectivity of ibuprofen as a free acid and its various alkyl esters (methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and isoamyl esters) derivatives were tested at different temperatures. Every tested stationary phase was capable of the chiral separations of ibuprofen in its free acid form. The less strong included S optical isomers eluted before R optical isomers in every separate case. The results offer to draw transportable guidelines for the chiral selectivity vs. analyte structures. It was recognized that the S isomers of free ibuprofen acid showed an overloading phenomenon, but the R isomer did not. The results were supported by molecular modeling studies.
Subject(s)
Ibuprofen , Ibuprofen/chemistry , Chromatography, Gas/methods , Stereoisomerism , Cyclodextrins/chemistry , Models, Molecular , Methylation , Anti-Inflammatory Agents, Non-Steroidal/chemistry , gamma-Cyclodextrins/chemistryABSTRACT
Dexamethasone (DEX) has been demonstrated to inhibit the inflammatory corneal neovascularization (CNV). However, the therapeutic efficacy of DEX is limited by the poor bioavailability of conventional eye drops and the increased risk of hormonal glaucoma and cataract associated with prolonged and frequent usage. To address these limitations, we have developed a novel DEX-loaded, reactive oxygen species (ROS)-responsive, controlled-release nanogel, termed DEX@INHANGs. This advanced nanogel system is constructed by the formation of supramolecular host-guest complexes by cyclodextrin (CD) and adamantane (ADA) as a cross-linking force. The introduction of the ROS-responsive material, thioketal (TK), ensures the controlled release of DEX in response to oxidative stress, a characteristic of CNV. Furthermore, the nanogel's prolonged retention on the corneal surface for over 8 h is achieved through covalent binding of the integrin ß1 fusion protein, which enhances its bioavailability. Cytotoxicity assays demonstrated that DEX@INHANGs was not notably toxic to human corneal epithelial cells (HCECs). Furthermore, DEX@INHANGs has been demonstrated to effectively inhibit angiogenesis in vitro. In a rabbit model with chemically burned eyes, the once-daily topical application of DEX@INHANGs was observed to effectively suppress CNV. These results collectively indicate that the nanomedicine formulation of DEX@INHANGs may offer a promising treatment option for CNV, offering significant advantages such as reduced dosing frequency and enhanced patient compliance.