Amount Of Cyclodextrin Research Articles

Supramolecular Complexes of Plant Neurotoxin Veratridine with Cyclodextrins and Their Antidote-like Effect on Neuro-2a Cell Viability.

Veratridine (VTD) is a plant neurotoxin that acts by blocking the voltage-gated sodium channels (VGSC) of cell membranes. Symptoms of VTD intoxication include intense nausea, hypotension, arrhythmia, and loss of consciousness. The treatment for the intoxication is mainly focused on treating the symptoms, meaning there is no specific antidote against VTD. In this pursuit, we were interested in studying the molecular interactions of VTD with cyclodextrins (CDs). CDs are supramolecular macrocycles with the ability to form host–guest inclusion complexes (ICs) inside their hydrophobic cavity. Since VTD is a lipid-soluble alkaloid, we hypothesized that it could form stable inclusion complexes with different types of CDs, resulting in changes to its physicochemical properties. In this investigation, we studied the interaction of VTD with β-CD, γ-CD and sulfobutyl ether β-CD (SBCD) by isothermal titration calorimetry (ITC) and nuclear magnetic resonance (NMR) spectroscopy. Docking and molecular dynamics studies confirmed the most stable configuration for the inclusion complexes. Finally, with an interest in understanding the effects of the VTD/CD molecular interactions, we performed cell-based assays (CBAs) on Neuro-2a cells. Our findings reveal that the use of different amounts of CDs has an antidote-like concentration-dependent effect on the cells, significantly increasing cell viability and thus opening opportunities for novel research on applications of CDs and VTD.

Development and evaluation of drug-cyclodextrin-polymer ternary system of Cefuroxime axetil to enhance the solubility and dissolution efficiency

Cefuroxime axetil (CA) is BCS class II drug and has 55% absolute oral bioavailability due to poor aqueous solubility hence the present work is an attempt to enhance the solubility and hence dissolution of CA by inclusion complexation with natural Cyclodextrins (CDs). The complexation efficiency of Cyclodextrin is low and hence large amount of CDs are required to solubilize small amount of poorly water-soluble drug. To overcome this limitation the hydrophilic polymers were used to improve the complexation efficiency of cyclodextrin through the formation of ternary complexes. In association with water soluble polymers like Polyvinyl Pyrrolidone (PVP) and Hydroxy Propyl Methyl Cellulose (HPMC) the complexation potential CDs (β-CD and HP-β-CD) was found to be improved which was analyzed by comparative evaluation of binary (drug: cyclodextrin) and ternary system (drug:cyclodextrin:polymer). Binary and ternary complexes were prepared by lyophilization method. On the basis of physicochemical characterization techniques like TLC, FTIR, DSC, and XRPD, the complex formation between CA, CD and water-soluble polymers was confirmed. The dissolution rate studies were also carried out in order to assess the in-vitro performance of complexes. Drug-HP-β-CD-HPMC lyophilized system showed higher solubility and dissolution rate as compared to other systems.

Remdesivir interactions with sulphobutylether-β-cyclodextrins: A case study using selected substitution patterns

Modified cyclodextrins (CDs) consist of a distribution of different structures with different number and location of the substituted groups. Among the most important applications of these molecules is their use as an enabling excipient in pharmaceutical formulations to provide the necessary solubility, stability and bioavailability for a drug to be effectively used. The most typical interaction mechanism of small molecular groups with CDs is the formation of host–guest inclusion complexes. The thermodynamic affinity constant between CDs and drugs should not be too strong, since then the biological activity could be negated by the formation of the complex. In the opposite scenario, if the affinity constant is too weak, the complex is barely formed and the amount of CD required in the formulation may become too great. Thus, a balance between the affinity of the CD and the drug is necessary for an optimal formulation. Additionally in the case of modified CDs and specific drug complexes there are further questions concerning the effect that the locations and number of substitutions plays in complexation. In the present work, this question is explored by using sulphobutylether-β-cyclodextrin and remdesivir, the only antiviral medication currently approved by the United States Food and Drug Administration for treating COVID-19, as a case study. This paper presents results from an orthogonal study using isothermal titration calorimetry measurements and biased molecular dynamics simulations that provide complementary information. Isothermal titration calorimetry delves into the global impact of the species distribution while molecular dynamics simulations deals with specific chemical structures. The goal is to provide useful information to optimize pharmaceutical formulations based on modified CDs, specifically in the case of remdesivir, used to treat SARS-CoV-2 infection, although the main conclusions could be extended to the interaction of other drugs with modified cyclodextrins.

Main Applications of Cyclodextrins in the Food Industry as the Compounds of Choice to Form Host-Guest Complexes.

Cyclodextrins (CDs) are cyclic oligomers broadly used in food manufacturing as food additives for different purposes, e.g., to improve sensorial qualities, shelf life, and sequestration of components. In this review, the latest advancements of their applications along with the characteristics of the uses of the different CDs (α, β, γ and their derivatives) were reviewed. Their beneficial effects can be achieved by mixing small amounts of CDs with the target material to be stabilized. Essentially, they have the capacity to form stable inclusion complexes with sensitive lipophilic nutrients and constituents of flavor and taste. Their toxicity has been also studied, showing that CDs are innocuous in oral administration. A review of the current legislation was also carried out, showing a general trend towards a wider acceptance of CDs as food additives. Suitable and cost-effective procedures for the manufacture of CDs have progressed, and nowadays it is possible to obtain realistic prices and used them in foods. Therefore, CDs have a promising future due to consumer demand for healthy and functional products.

Facile cyclodextrin-assisted synthesis of highly active CuO-CeO2/MCF catalyst for CO oxidation

A CuO-CeO2/MCF catalyst was prepared by cyclodextrin-assisted co-impregnation (CC/M-CD). For comparison, a reference catalyst was prepared by traditional wet impregnation (CC/M). The catalysts were characterized by ICP-OES, XRD, Raman, N2-physisorption, TEM, EDS mapping, XPS, in situ DRIFTS, H2-TPR, and CO-TPD. The results show that Cu and Ce species of the CC/M-CD catalyst disperse more homogeneously, and the CC/M-CD catalyst has a larger surface area, more amounts of Cu+ and Ce3+ species, enhanced interaction between CuO and CeO2, and thus exhibits higher catalytic activity in CO oxidation. Additionally, the kind and amount of cyclodextrin used in the impregnating solutions have no distinct effect on the activity of CC/M-CD prepared by the cyclodextrin-assisted co-impregnation.

Development of prednisolone-containing eye drop formulations by cyclodextrin complexation and antimicrobial, mucoadhesive biopolymer.

PurposeThe formulation of topical ophthalmic products with appropriate therapeutic effect and patient compliance is a major challenge. To increase the efficiency of the ocular delivery of the drug, the enhancement of water solubility and the contact time of the drug on the surface of the cornea are necessary. In this work, prednisolone (PR)-containing eye drops were formulated with antimicrobial, mucoadhesive biopolymer and PR–cyclodextrin inclusion complex. This approach can be used for the development of innovative ophthalmic formulations.Materials and methodsAfter adjusting the optimal physiological parameters, the amount of the required cyclodextrin for the highest penetration of PR was determined by dialysis membrane diffusion study. The viscosity, surface tension and mucoadhesion of the eye drops were measured. The microbiological effectiveness of zinc-hyaluronate (ZnHA) was investigated by a standard method of the European Pharmacopoeia.ResultsIn this case, no significant difference of surface tension was measured in products with different amounts of cyclodextrin. According to the results of the tensile test, ZnHA as a mucoadhesive biopolymer improves the mucoadhesion of ophthalmic products. The antimicrobial stability of formulations preserved by ZnHA meets requirement B of the European Pharmacopoeia.ConclusionIt can be stated that the innovative PR-containing compositions are suitable for producing mucoadhesive, properly preserved aqueous ophthalmic solutions with increased bioavailability attributes.

Cyclodextrin-assisted synthesis of tailored mesoporous silica nanoparticles.

Mesoporous silica nanoparticles (MSNs) have sparked considerable interest in drug/gene delivery, catalysis, adsorption, separation, sensing, antireflection coatings and bioimaging because of their tunable structural properties. The shape, size and pore structure of MSNs are greatly influenced by the type of additives used, e.g., solvent and pore-templating agent. Here, we studied the influence of cyclodextrin (CD) molecules on the formation of MSNs. The nanoparticles over 100 nm in diameter were synthesized by surfactant-templated, hydrolysis–polycondensation reactions in the presence of pristine CD (β-CD) or hydroxypropyl-functionalized CDs (HP-γ-CD and HP-β-CD). Depending on the formulation conditions, differently shaped MSNs, such as bean-like, spherical, ellipsoid, aggregate and faceted were generated. The morphology and size of MSNs varied with the CD-type used. Generally, spherical particles were obtained with β-CD, while a faceted morphology was observed for the particles synthesized using HP-CDs. The particle size could be tuned by adjusting the amount of CD used; increasing the CD concentration led to larger particles. MSNs synthesized in the presence of β-CD displayed a smaller particle size than those produced with HP-functional CDs. FTIR, TGA and solid-state 13C NMR demonstrated the adsorption of CDs on the particle surfaces. The proposed concept allows for the synthesis of silica nanoparticles with control over particle shape and size by adjusting the concentration of additives in a simple, one-pot reaction system for a wide range of applications.

Enzymatic Synthesis of Resveratrol α-Glycosides from β-Cyclodextrin-Resveratrol Complex in Water

Although resveratrol (3,5,4′-trihydroxy-stilbene) is one of the most studied natural product because of its biological properties such as antioxidant or anticancer, its low water solubility and stability (influenced by pH, light and increased temperature), as well as its propensity to oligomerize, limit its bioavailability and applications in nutraceutic, cosmetics or pharmaceutical industries. Besides, resveratrol production at the multigram scale through vine cell culture is limited by the tedious extraction of pure resveratrol from the bioconversion medium due to its complexation by cyclodextrins, the latter being used as elicitors in the bioproduction process. In this work, we have been able to overcome all these drawbacks by performing a single organic solvent-free enzymatic α-glycosylation directly from the β-cyclodextrin-resveratrol complex in water using β-cyclodextrin as glycoside-donor. The combined effects of five parameters (CGTase amount, cyclodextrin amount, cyclodextrin/resveratrol ratio, p...

Nanoparticle structure transformation of mPEG grafted chitosan with rigid backbone induced by α-cyclodextrin

This paper presented an interesting nanoparticle-based drug delivery system with morphology transition behavior depending on the content of exposed PEG chain on the particle surface, which is adjustable by addition of different amount of cyclodextrin (α-CD). The effect of α-CD inclusion to the self-assembly behavior of methoxy polyethylene glycol (mPEG) grafted chitosan (CS) was studied. The results showed that the mPEG grafted chitosan (mPEG-g-CS) forms self-assembled nanoparticles with either micelle or hollow sphere morphology depending on the ratio of α-CD to mPEG, as characterized by atomic force microscopy (AFM), transmission electron microscopy (TEM), and X-ray diffraction (XRD). Their sizes and zeta potential increased from 257.6 nmto 768.2nm and from +4.5mV to +11.6mV, respectively, with the increasing amount of α-CD. The correlation between zeta potential and particle size of α-CD/mPEG-g-CS nanoparticles indicated varied PEG density on surface of nanoparticles. Based on the above experimental observations, a likely mechanism for the morphological transition of the rod-coil graft copolymer mPEG-g-CS was proposed.

Cyclodextrins: structure, physicochemical properties and pharmaceutical applications

Since their discovery over 100 years ago cyclodextrins (CDs) have been the subject of numerous scientific publications. In 2016 alone CDs were the subject of over 2200 research articles published in peer-reviewed journals and mentioned in over 2300 patents and patent applications, many of which were on pharmaceutical applications. Natural CDs and their derivatives are used as enabling pharmaceutical excipients that enhance aqueous solubility of poorly soluble drugs, increase drug permeability through biological membranes and improve drug bioavailability. Unlike conventional penetration enhancers, their hydrophilic structure and high molecular weight prevents them from penetrate into lipophilic membranes leaving biological membranes intact. The natural CDs and some of their derivatives have monographs in pharmacopeias and are also commonly used as food additives and in toiletry products. CDs form inclusion complexes with lipophilic moieties of hydrophobic drugs. Furthermore, CDs are able to form non-inclusion complexes and self-assembled aggregates; small and large complex aggregates with micellar-like structures that can enhance drug solubility. Excipients commonly used in pharmaceutical formulations may have additive or inhibiting effect on the CD solubilization. Here various methods used to investigate CD aggregate formation are reviewed as well as techniques that are used to increase the solubilizing effects of CDs; methods that enhance the apparent intrinsic solubility of drugs and/or the complexation efficacy and decrease the amount of CD needed to develop CD-containing pharmaceutical formulations. It will be explained how too much or too little CD can hamper drug bioavailability, and the role of CDs in solid dosage forms and parenteral formulations, and examples given on how CDs can enhance drug delivery after ocular, nasal and pulmonary administration.

Highly-sensitive electrocatalytic determination for toxic phenols based on coupled cMWCNT/cyclodextrin edge-functionalized graphene composite

Highly-sensitive electrocatalytic determination of toxic phenol compounds is of significance in environmental monitoring due to their low degradation and high toxicity to the environment and humans. In this paper, a rapid and sensitive electrochemical sensor based on coupled carboxyl-multi-walled carbon nanotube (cMWCNT) and cyclodextrin (CD) edge-functionalized graphene composite was successfully employed towards trace detection of three typical phenols (4-aminophenol, 4-AP; 4-chlorophenol, 4-CP; 4-nitrophenol, 4-NP). The morphology studies from scanning electron microscope and transmission electron microscope analysis revealed that cMWCNTs as conductive bridges were successfully incorporated into CD edge-functionalized graphene layers. Further, The electrocatalytic detection performance of the 3D simultaneously reduced and self-assembled sensing architecture (GN-CD-cMWCNT) with trace amounts of CDs was evaluated. The electrochemical studies demonstrated that GN-CD-cMWCNT displays excellent electrocatalytic activity, high sensitivity and stability. Under optimal conditions, the current responses of 4-AP, 4-CP and 4-NP are linear to concentrations over two different ranges, with low detection limit of 0.019, 0.017 and 0.027μM (S/N=3), respectively. And, GN-CD-cMWCNT shows an excellent anti-interference ability against electroactive species and metal ions. In addition, validation of the applicability of the presented sensor was also performed for the determination of three phenols in tap water sample with satisfactory results.

Synthesis and characterization of poly(2-hydroxyethylacrylate)/β-cyclodextrin hydrogels obtained by frontal polymerization

For the first time, the synthesis of polymeric hydrogels containing cyclodextrins (CDs) obtained by frontal polymerization (FP) is reported. In particular, the effects of CDs on poly(2-hydroxyethylacrylate) hydrogel properties are investigated. In a first series of materials, β-cyclodextrin is dispersed into the polymer matrix, while in the second one acryloyl-β-cyclodextrin is grafted to poly(2-hydroxyethylacrylate) chains. FP parameters (front velocity and maximum temperature), swelling properties, glass transition temperatures and mechanical properties of the hydrogels are studied. Results show that both types of cyclodextrin influence the above properties, and the major effects are found for concentration higher than 1mol% of acryloyl-β-cyclodextrin. Namely, a significant increase of glass transition temperature and of compression moduli are found. Finally, this study demonstrates that FP is a convenient technique to obtain CD-containing hydrogels, in which the type and amount of cyclodextrin can be suitably modulated to tune polymer properties, in function of the desired hydrogel applications.

Preparation and adsorption properties of laponite–cyclodextrin complex

Laponite–cyclodextrin complex was synthesised by amidation of carboxylated cyclodextrin and amine-modified laponite, which were first modified by amine-terminated silane coupling agents with different chain lengths and functional groups. The structures of the laponite before and after modification were characterised by Fourier transform infrared and proton nuclear magnetic resonance. The effect of the silane coupling agents on the loading amounts of cyclodextrin onto laponite was investigated by thermogravimetric analyser. The results showed that the loading amounts of cyclodextrin and silane coupling agents increased with the increasing chain lengths and the decreasing alkoxyl groups of silane coupling agents. The laponite–cyclodextrin complexes gathered the advantages of adsorbing aromatic organic compounds by cyclodextrin via host–guest inclusion interaction and adsorbing metal ions by laponite via ion exchange. The laponite–cyclodextrin complex presents great applications in the aspect of wastewater treatment.

Cyclodextrin-Modified Film Dosage Forms for Oral Candidiasis Treatment

Oral candidiasis is a common disease in patients with dry mouth. In this study, film dosage forms (FD) incorporating miconazole nitrate, an antifungal agent, were prepared with water-soluble polysaccharide and cyclodextrin (CD). The dissolution profiles of the drug from the FDs were investigated in limited dissolution medium. Soft films were obtained from sodium alginate containing 0.5% α-CD, β-CD, or γ-CD. Most FDs were easy to handle, though the film tearing resistance was lower than that of CD-free FDs. Addition of CD to the FD accelerated the drug dissolution rate. Interestingly, this phenomenon was also observed in FDs prepared with pullulan. In contrast, acceleration of the drug dissolution rate was not observed when CD polymer was added to the base solution. The initial drug dissolution rate was controllable by the amount of CD added to the FD. Therefore, FDs prepared with these materials are useful to treat oral candidiasis in patients with dry mouth syndrome.

Temperature Dependence of the Complexation Mechanism of Celecoxib and Hydroxyl-β-cyclodextrin in Aqueous Solution.

Hydroxypropyl-β-cyclodextrin (HP-β-CD) is commonly used as a complexation reagent to solubilize compounds with poor aqueous solubility to improve in vivo dosing. However, the degree of solubility enhancement was often limited by the formation of only a 1:1 complex and a low complexation constant (K). Such a limitation can be significantly improved by the formation of 1:2 complexes in some cases. Despite the understanding of the solubility advantage of the formation of the 1:2 complexes, there is no systematic understanding that could drive for the formation of 1:2 complexes. Thus, in most cases, the formation of 1:2 complexes was limited by observation bases. In this study, we pioneer the usages of molecular dynamics (MD) simulation to understand the phenomena of a model drug of celecoxib (CCB) and HP-β-CD. It has been reported that celecoxib (CCB) forms 1:1 complexes with cyclodextrin in solution; however, some data suggest the existence of a 1:2 complex. The simulation results suggest that a transition state of CCB and HP-β-CD may exit at a higher temperature of CCB and HP-β-CD; a model drug, such as celecoxib (CCB), that is known to form 1:1 complexes can achieve a higher degree of complexation (1:2) and obtain much improved solubility when the same amount of cyclodextrin was used and demonstrated in vitro. The simulation results of CCB and HP-β-CD could be a model system that may provide important insights into the inclusion mechanism.

Reused cyclodextrin as a new way to deliver and enhance drug loading onto ion exchange resin

Context: Cyclodextrins could improve drug solubility and drug loading onto ion exchange resins. Moreover, the remaining cyclodextrin in the solution might be reused for drug solubility enhancement and drug loading onto resin.Objectives: To investigate the application of fresh and reused cyclodextrin to improve drug solubility and drug loading onto resin.Methods: The inclusion complexes were prepared and characterized using β-cyclodextrin (βCD) and 2-hydroxypropyl-β-cyclodextrin (HPβCD). The drug solution was loaded onto resin with and without cyclodextrin. Then, the remaining cyclodextrin was reused for the complex and the drug loading process.Results and discussion: Improved drug solubility was observed when using cyclodextrins. The complex was successfully formed with 1:1 stoichiometry. The increase in drug solubility with cyclodextrins improved drug loading onto resin. The cyclodextrins delivered drug to bind with resin, forming resinate, and did not bind with the resinate themselves, which was confirmed by quantification of the amount of cyclodextrin in drug loading solution before and after drug loading process. Therefore, cyclodextrins were available to reuse for drug loading without affecting the percentage of drug loading.Conclusions: Reused cyclodextrin is a novel way to deliver and enhance drug loading onto resin for development of an ion exchange-based drug delivery system.

Inclusional association as studied by the drying dissipative structure. Part 3. Drying pattern of aqueous mixtures of β-cyclodextrin and n-alkyltrimethylammonium bromide

Macroscopic and microscopic drying patterns were observed on a cover glass and a watch glass during the course of dryness of aqueous mixtures of β-cyclodextrin (βCD) with n-alkyltrimethylammonium bromide (alkyl: n-decyl, n-dodecyl, n-tetradecyl, and n-hexadecyl). Macroscopic patterns of the broad rings and the spoke lines appeared. The inclusional association constants of βCD with the cationic surfactants were determined from the bent points in the curves of the drying broad-ring size vs. surfactant concentration when a finite amount of cyclodextrin presents. The short and thick rod-like microscopic drying patterns were observed for the inclusional complexes.

Cyclodextrin Formation Initiated by Enzyme Debranching Reaction On Amylopectin Branch Chain Of Tapioka

Degradation of starch by the glucosyltransferase enzyme (CGTase) to produce the primary product of chainsplitting undergoes an intramolecular reaction without the participation of water molecule. From this process, α-1,4-Linked cyclic product, known as cyclodextrins, are formed. The aim of the research was to cut amylopectinbranch in order to produce one straight chain, to optimize cyclic reaction formation cyclodextrin by CGTase. Theresearch was devided into 3 stages; (1) debranching enzyme concentration estimation (5,10,15,20, and 25 unit/gram) and the length of otimum reaction to produce straight chain for 5 hours which sample was taken each hour,(2) reaction length time estimation to form cyclodextrin in order to use debranching products (straight chain) assubstrates, the reaction length for 360 minutes and sample taken each for 30 minutes, and (3) the best substrateconcentration for straight chain (20-40% w/v) to produce cyclodextrin. The result showed that enzyme concentrationtreatment and optimal length reaction will produce straight chain with enzyme concentration of 14 units/gram for3 hours and straight chain product of 20 units/gram for 1 hour with straight chain product of 83.5%. The optimumlength of reaction for cyclodextrin formation from amylose produced from the de-branching process was 240minutes. The amount of cyclodextrin produced was 143.45 g/L with conversion value of 47.81% at 30% (w/v)substrate concentration. Highest yield of cyclodextrin (154,28 g/L) and conversion value of 44.08% was obtained at35% (w/v) substrate concentration

Gamma-Cyclodextrin Production Using Cyclodextrin Glycosyltransferase from Bacillus clarkii 7364

The production of cyclodextrins (CDs) by cyclodextrin glycosyltransferase (CGTase) from Bacillus clarkii 7364 was studied. Forty-seven percent (w/w) conversion rate to γ-CD was obtained in the process performed by reacting 5 U per gram of starch CGTase with 15 % (w/v) soluble starch in 0.025 M sodium phosphate-NaOH buffer (pH 12) at 55 °C in the presence of 2 % (w/v) glycyrrhizic acid. Meanwhile, the ratio of γ:β-CD was 89:11, with negligible formation of α-CD. Under these conditions, there is a significant increase in overall production of CDs and a marked change in product selectivity for γ-CD. The possible mechanisms were discussed upon different product profiles with respect to the size and amount of CDs synthesized at different reaction conditions. The approach described here can be easily applied to an enzymatic process for the production of γ-CD on an industrial scale, and such high selectivity, at high conversions, is especially attractive from a commercial perspective.

Cyclodextrins and ternary complexes: technology to improve solubility of poorly soluble drugs

Cyclodextrins (CDs) are cyclic oligosaccharides composed of D-glucopyranoside units linked by glycosidic bonds. Their main property is the ability to modify the physicochemical and biological characteristics of low-soluble drugs through the formation of drug:CD inclusion complexes. Inclusion complexation requires that host molecules fit completely or partially within the CD cavity. This adjustment is directly related to the physicochemical properties of the guest and host molecules, easy accommodation of guest molecules within the CD cavity, stoichiometry, therapeutic dose, and toxicity. However, dosage forms may achieve a high volume, depending on the amount of CD required. Thus, it is necessary to increase solubilization efficiency in order to use smaller amounts of CD. This can be achieved by adding small amounts of water-soluble polymers to the system. This review addresses aspects related to drug complexation with CDs using water-soluble polymers to optimize the amount of CD used in the formulation in order to increase drug solubility and reduce dosage form volume.