Types Of Cyclodextrins Research Articles

Simultaneous enantioseparation of citrus flavonoids in chiral microemulsion electrokinetic chromatography using deep eutectic solvents

A novel, deep eutectic solvent (DES)-assisted sodium cholate (SC)-chiral microemulsion electrokinetic chromatography method is presented for separation of five flavonoid glycoside enantiomers, namely hesperidin, naringin, narirutin, eriocitrin, and neoeriocitrin. Herein, we develop a novel, green DES, whose addition considerably enhances the separation performance through multiple synergistic effects. A series of factors notably affecting chiral separation are systematically optimized: type and concentration of cyclodextrin, DES, and SC, oil phase type, and pH. The microemulsion comprises 0.5 % (v/v) n-octanol, 0.6 % (v/v) DES prepared using betaine and citric acid, 20 mM 2-HP-β-CD, 100 mM scdium cholate hydrate, and 15 mM borax buffer under the optimized conditions. Enantioseparations of the five enantiomers are achieved within 7 min, with resolutions ranging from 1.29 to 2.88. The method developed provides an innovative and effective way for chiral separation of enantiomers in complex food matrices.

Complexation of telmisartan with cyclodextrins as a tool of solubility enhancement: A comparative analysis of influence of the cyclodextrin type and method of solid dispersion preparation

Cardiovascular telmisartan (TMS) was complexed with modified cyclodextrins (CD) aiming at improvement of its poor solubility which results into low bioavailability. Inclusion complexes with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) and sulfobutylether-β-cyclodextrin (SBE-β-CD) in liquid and solid state was evaluated for first time. Phase solubility isotherm diagrams of TMS versus the CD concentration were plotted in a buffer pH 7.4. It was found that TMS/CD complexes are formed in solution in an equimolar stoichiometric ratio of 1:1. The aqueous solubility of TMS with the addition of 0.05 mol·L−1 HP-β-CD increased by 23 times and was 38.9·10−5 mol·L−1, and the presence of the same amount of SBE-β-CD in solution increased the solubility of the drug by 7 times, reaching a value of 12.6·10−5 mol·L−1.The binding constants were found to 468 and 114 L·mol−1 for HP-β-CD and SBE-β-CD, respectively. Novel solid forms of TMS with both CDs were prepared using the grinding and evaporation approaches. Successful formation of supramolecular TMS/HP-β-CD and TMS/SBE-β-CD solid complexes was confirmed by FTIR, PXRD, DSC, TGA and SEM. The residual crystallinity of all obtained solid dispersions of TMS/CD did not exceed 10 %. Supersaturation was observed during the dissolution of all the solid complexes. The grinding technique was found to be more advantageous as it ensured the biggest improvement of the drug maximum concentration in the aqueous solution: the TMS solubility in the TMS/HP-β-CD(gr) and TMS/SBE-β-CD(gr) solid complexes increased by 27 and 33 times, respectively. Besides, polyvinyl pyrrolidone (PVP) and polyethylene glycol (PEG) were tested as crystallization inhibitors. Addition of 1 wt% PVP as a stabilizer is a promising approach for the preparation of TMS pharmaceutical formulations with improved bioavailability.

Regulatory effects of cyclodextrins on light-responsive phase transition behaviors of poly(N-isopropylacrylamide-co-N-(4-phenylazophenyl)methylacrylamide)

The physicochemical properties of light-responsive polymers have attracted widespread attention due to their ability to be precisely and conveniently modulated by light without additives or contact. Here, we report a thermo/light dual-responsive polymer, PNMA, synthesized through the free radical copolymerization of azobenzene derivative (mAzo) and N-isopropylacrylamide (NIPAM) monomers. By switching between 365 nm UV light and 450 nm visible light, the E/Z photoisomerization of the light-responsive mAzo can be reversibly controlled, and thereby adjusting the conformational changes of the PNMA polymer chain. Significantly, the stretching and contraction conformations of PNMA polymer chains can be manipulated by incorporating different types of cyclodextrins. A comprehensive comparative study was conducted to determine the light-controlled binding and dissociation processes between the azobenzene units and CDs (α-CD, β-CD and γ-CD), the influences of CDs on the photoisomerization kinetics and complexation constants of azobenzene with CDs, as well as the effect of CDs on the light-responsive phase transition behaviors of PNMA. Our results highlight the superior advantage of α-CD in constructing light-responsive systems with significant changes in hydrophilicity. Notably, by tuning the concentration of α-CD and the proportion of mAzo in PNMA, the range of light-induced thermosensitive response is significantly expanded. This study is the first to present a comparative study on the effects of three CDs on the thermo/light dual-responsive properties of polymer systems based on PNIPAM and azobenzene, providing new ideas for CD selection in the design and construction of advanced light-responsive materials based on light-responsive guest-host dissociation or hydrophilic changes of azobenzene/CD complexes.

Cyclodextrin-assisted extraction as a green alternative for the recovery of phenolic compounds from Helichrysum plicatum DC. flowers

Helichrysum plicatum DC. is an important source of bioactive secondary metabolites with a variety of pharmacological activities. To obtain highly potent extracts with the maximum level of phenolic glycosides and total phenolic compounds, this study aimed to establish an eco-friendly cyclodextrin-assisted extraction procedure from H. plicatum flowers. Response surface methodology (RSM) and artificial neural networks (ANN) were used to optimize the ultrasound-assisted extraction (UAE) by evaluating sonication temperature, time, concentrations of ethanol and two types of cyclodextrins (β-CD and HP-β-CD). Comprehensive statistical validation revealed better predicting capacity of the created ANN models compared to the traditional RSM. The highest positive effects were observed for the ethanol concentration and the extraction temperature. Both types of CDs showed not only positive impact on the extraction efficiency of bioactives, but also on their stability after exposure to stress conditions. Molecular docking was used to additionally reveal interactions within the studied inclusion complexes. Conclusively, the HP-β-CD-assisted extraction conducted at 80 °C for 40 min, utilizing 62% ethanol and 1.60% HP-β-CD, was the most optimal due to its ability to minimize ethanol consumption while achieving maximal recovery of bioactives, in comparison to β-CD (80%). Under these optimized conditions, experimentally obtained results for isoquercitrin (0.50 mg/g DW), kaempferol-3-O-glucoside (5.83 mg/g DW), apigenin-7-O-glucoside (1.34 mg/g DW), and total polyphenolic (28.51 mg GAE/g DW) content were in agreement with the values predicted by ANN.

Cyclodextrins as therapeutic drugs for treating lipid metabolism disorders.

This study sought to systematically compare the efficacy and mechanism of cyclodextrins as drug interventions in lipid metabolism diseases, potentially providing ideas for subsequent research directions and clinical applications. We used the bibliometric method for feature mining, applied VOSviewer software for clustering analysis, and applied content analysis for objective descriptions and accurate analysis. (1) We collected more than 50 studies, which is the basic database of this study. (2) The academic bubble map showed that this research area was popular in the United States. (3) Cluster analysis showed that the intensively studied diseases in this field were Niemann-Pick type C (NPC), atherosclerosis (AS), and obesity. The hot-spot cyclodextrin types were HP-β-CD. (4) Literature measurement revealed the involvement of 15 types of lipid metabolism diseases. Among them, NPC, diabetes, and obesity were studied in clinical trials. Dyslipidemia and AS have been reported relatively more frequently in animal experiments. The studies of cellular experiments provide insight into the molecular mechanisms that intervene in lipid metabolism diseases from multiple perspectives. The exploration of the molecular mechanisms by which cyclodextrins exert their pharmacological effects mainly revolves around lipid metabolism. It is worthwhile to investigate the role and mechanism of cyclodextrins in other lipid metabolism diseases. The potential efficacy evaluation of cyclodextrins as pharmaceutical drugs for oral or injectable formulations is less studied and may become a new focus in the future.

Enhancement of bioavailability and anti-inflammatory activity of inotodiol through complexation with γ-cyclodextrin

The aims of the present study were to fabricate an inclusion complex of inotodiol (INO) with cyclodextrin (CD) and to evaluate its bioavailability and anti-inflammatory activity. Different types of cyclodextrins in DDW were employed as host molecules, and INO dissolved in ethanol was added to the CD solutions during ultra-sonication. DSC and FTIR results showed that INO was complexed only with γ-cyclodextrin (γ-CD) efficiently at a molar ratio of 1:3 (INO1/γ-CD3). Large mean particle size (261.4 nm), high polydispersity index (0.497), and bimodal size distribution of INO1/γ-CD3 resulted from the formation of large aggregates after the inclusion complex formation. Following oral administration at the dose of 1.0 mg/kg for INO1/γ-CD3 group and the 2.0 mg/kg for INO group in mouse, the maximum inotodiol plasma concentration (Cmax) and the relative area under curve (AUC per 1 mg/kg dose) were 2.6- and 4.96-fold higher, respectively, in the INO1/γ-CD3 group than in the INO group. Anti-inflammatory activity analysis of INO was conducted using RAW264.7 cells stimulated by lipopolysaccharide, and the repression effect of INO on pro-inflammatory cytokines was enhanced by the complexation with γ-CD. Our findings suggest that INO1/γ-CD3 can be a potent therapeutic formulation for the treatment of inflammatory diseases.

Preparation of trans-Crocetin with High Solubility, Stability, and Oral Bioavailability by Incorporation into Three Types of Cyclodextrins.

Crocetin (CRT), an active compound isolated from saffron, exhibits several pharmacological activities, including anti-tumor and immune-regulatory activities, and is effective against myocardial ischemia and coronary heart disease; however, its low stability and solubility limit its clinical application. Therefore, we investigated CRT inclusion complexes (ICs) with three cyclodextrins-α-CD, HP-β-CD, and γ-CD-suitable for oral administration prepared using an ultrasonic method. Fourier transform infrared spectroscopy and powder X-ray diffraction indicated that the crystalline state of CRT in ICs disappeared, and intermolecular interactions were observed between CRT and CDs. 1H nuclear magnetic resonance and phase solubility studies confirmed CRT encapsulation in the CD cavity and the formation of ICs. In addition, we observed the morphology of ICs using scanning electron microscopy. All ICs showed a high drug encapsulation efficiency (approximately 90%) with 6500-10,000 times better solubilities than those of the pure drug. CRT showed rapid dissolution, whereas pure CRT was water-insoluble. The formation of ICs significantly improved the storage stability of CRT under heat, light, and moisture conditions. Further, the peak time of CRT in rats significantly decreased, and the relative bioavailability increased by approximately 3-4 times. In addition, the oral bioavailability of CRT IC was evaluated. Notably, the absorption rate and degree of the drug in rats were improved. This study illustrated the potential applications of CRT/CD ICs in the food, healthcare, and pharmaceutical industries, owing to their favorable dissolution, solubility, stability, and oral bioavailability.

Physico-chemical studies of inclusion complex between hydrocortisone and cyclodextrins

Hydrocortisone (HC) is widely utilized in the pharmaceutical field for various administration routes, including oral, parenteral, and topical routes. However, its application in ocular disease treatment as a solution is limited due to its poor aqueous solubility. To address this limitation, in this study we aimed to investigate different types of cyclodextrins (CDs) to identify the most effective CD for improving the inherent solubility of HC. Results from scanning electron microscopy, rheology and differential scanning calorimetry (DSC) demonstrated the formation of inclusion complexes, while isothermal titration calorimetry (ITC) investigations accurately determined the thermodynamic parameters associated with the formation of complexes between HC and HPβCD or βCD, at 25 and 37 °C. Additionally, phase solubility studies in PBS buffer at 37 °C confirmed the formation of stable inclusion complexes. Collectively, results indicated that HPβCD was the most effective CD in enhancing the intrinsic solubility of HCs in PBS highlighting its potential for improving the solubility and formulation of HC-based pharmaceutical products.

Cyclodextrins for the Delivery of Bioactive Compounds from Natural Sources: Medicinal, Food and Cosmetics Applications.

Cyclodextrins have gained significant and established attention as versatile carriers for the delivery of bioactive compounds derived from natural sources in various applications, including medicine, food and cosmetics. Their toroidal structure and hydrophobic cavity render them ideal candidates for encapsulating and solubilizing hydrophobic and poorly soluble compounds. Most medicinal, food and cosmetic ingredients share the challenges of hydrophobicity and degradation that can be effectively addressed by various cyclodextrin types. Though not new or novel-their first applications appeared in the market in the 1970s-their versatility has inspired numerous developments, either on the academic or industrial level. This review article provides an overview of the ever-growing applications of cyclodextrins in the delivery of bioactive compounds from natural sources and their potential application benefits.

Analytical method development supported by DoE-DS approach for enantioseparation of (S,S)- and (R,R)-moxifloxacin

In this paper, method for enantiomeric purity testing of fourth-generation fluoroquinolone, moxifloxacin hydrochloride, was developed and validated. Exceptional enantioselectivity for this assay was achieved using cyclodextrin type Chiral Stationary Phase (CSP), phenylcarbamate-β-cyclodextrin CSP, and mobile phase consisted of acetonitrile and triethylammonium acetate (TEAA) buffer. Analytical Quality by Design (AQbD) methodology, comprising Design of Experiments (DoE) - Design Space (DS) approach, was used for method development. In order to select appropriate Critical Method Parameters (CMPs), risk assessment was done using combined three step strategy that involved Ishikawa diagram - CNX (Control, Noise and eXperimental) - FMEA (Failure Mode and Effect Analysis). Three CMPs were further selected and investigated in this study: acetonitrile content in the mobile phase (30–50%, v/v), triethylamine content in the TEAA buffer (0.1–1.5%, v/v) and aqueous phase pH (3.5–4.5). Monte Carlo simulations were performed and 3D-DS was computed. One point situated in the center of 3D-DS was selected as working point for method validation, with the following values of CMPs: acetonitrile content in the mobile phase set to 37% (v/v), triethylamine content in TEAA 0.8% and pH value of the aqueous phase set at 4.0. Also, 2D-DS was created (with fixed one factor – pH value of aqueous phase at 4.0) which also gave us confirmation that the selection of working conditions was suitable. The proposed enantioselective method was further on tested for its quantitative robustness, as well as for its suitability for the intended purpose through validation studies.

Host Dynamics under General-Purpose Force Fields.

Macrocyclic hosts as prototypical receptors to gaseous and drug-like guests are crucial components in pharmaceutical research. The external guests are often coordinated at the center of these macromolecular containers. The formation of host-guest coordination is accompanied by the broken of host-water and host-ion interactions and sometimes also involves some conformational rearrangements of the host. A balanced description of various components of interacting terms is indispensable. However, up to now, the modeling community still lacks a general yet detailed understanding of commonly employed general-purpose force fields and the host dynamics produced by these popular selections. To fill this critical gap, in this paper, we profile the energetics and dynamics of four types of popular macrocycles, including cucurbiturils, pillararenes, cyclodextrins, and octa acids. The presented investigations of force field definitions, refitting, and evaluations are unprecedently detailed. Based on the valuable observations and insightful explanations, we finally summarize some general guidelines on force field parametrization and selection in host-guest modeling.

Tunable Synthesis of Sub‐20 nm Gold Nanoparticles Capping with Cyclodextrin for Host–Guest Molecular Recognition on Nano‐Surface

AbstractGold nanoparticles capping with three types of natural cyclodextrins are synthesized, allowing for precise control over their sizes ranging from 9 to 20 nm. These nanoparticles exhibit remarkable colloidal stability during long‐term storage, as well as excellent tolerance to saline, acidic, and alkaline conditions. Importantly, the assembly of nanoparticles is performed by using the silica nanospheres functionalized with cinnamyl group and the gold nanoparticle capping with three types of cyclodextrin, highlighting the selective formation of core‐satellite superstructure based on the host–guest molecular recognition on nano‐surface between different nanoparticles.

Mechanistic insight of α-mangostin encapsulation in 2-hydroxypropyl-β-cyclodextrin for solubility enhancement

α-Mangostin is the most abundant compound contained in the mangostin (Garcinia mangostana L.) plant which have been developed and proven to have many promising pharmacological effects. However, the low water solubility of α-mangostin causes limitations in its development in clinical purpose. To increase the solubility of a compound, a method currently being developed is to make drug inclusion complexes using cyclodextrins. This research aimed to use in silico techniques namely molecular docking study and molecular dynamics simulation to explore the molecular mechanism and stability of the encapsulation of α-mangostin using cyclodextrins. Two types of cyclodextrins were used including β-cyclodextrin and 2-hydroxypropyl-β-cyclodextrin docked against α-mangostin. From the molecular docking results, it shows that the α-mangostin complex with 2-hydroxypropyl-β-cyclodextrin provides the lowest binding energy value of −7.99 Kcal/mol compared to β-cyclodextrin value of −6.14 Kcal/mol. The α-mangostin complex with 2-hydroxypropyl-β-cyclodextrin also showed good stability based on molecular dynamics simulation during 100 ns. From molecular motion, RDF, Rg, SASA, density, total energy analyzes, this complex shows increased solubility in water and provided good stability. This indicates that the encapsulation of α-mangostin with 2-hydroxypropyl-β-cyclodextrin can increase the solubility of the α-mangostin. Communicated by Ramaswamy H. Sarma

Extended q-Range X-Ray Scattering Reveals High-Resolution Structural Details of Biomacromolecules in Aqueous Solutions.

We communicate a feasibility study for high-resolution structural characterization of biomacromolecules in aqueous solution from X-ray scattering experiments measured over a range of scattering vectors (q) that is approximately two orders of magnitude wider than used previously for such systems. Scattering data with such an extended q-range enables the recovery of the underlying real-space atomic pair distribution function, which facilitates structure determination. We demonstrate the potential of this method for biomacromolecules using several types of cyclodextrins (CD) as model systems. We successfully identified deviations of the tilting angles for the glycosidic units in CDs in aqueous solutions relative to their values in the crystalline forms of these molecules. Such level of structural detail is inaccessible from standard small angle scattering measurements. Our results call for further exploration of ultra-wide-angle X-ray scattering measurements for biomacromolecules.

Comparative study of degree-based molecular descriptors of cyclodextrins through M-polynomial and NM-polynomial

Cyclodextrins are natural oligosaccharides used to increase the solubility of drugs. It has numerous applications in drug discovery, food storage and other fields. Loftsson et al. explained about applications of Cyclodextrins(CDs) in administrating the drugs through various ways. Jansook et al. has given insights into the structure, physicochemical properties and pharmaceutical applications of CDs. In the present work, cyclodextrin and its derivatives such as α, β, γ CDs are studied for which various degree and neighborhood degree-based topological indices are computed through M-polynomial and NM-polynomial respectively and the comparison of the indices for all three types of cyclodextrins are presented which are of great importance in QSPR/QSAR studies.

NANOSPONGES - A REVOLUTIONARY TARGETED DRUG DELIVERY NANOCARRIER: A REVIEW

Effective targeted drug delivery systems have long been a dream, but have been largely hampered by the complex chemistries involved in developing new systems. The creation of novel colloidal carriers known as nanosponges has the potential to resolve these issues. An innovative and developing technology called nanosponge provides regulated medication delivery for topical application. Highly porous nanosponges have a unique capacity to entrap active molecules and have the advantage of programmable release. Nanosponges are small three-dimensional porous structures about the size of nanometer that can contain many different drugs. These tiny sponges can move throughout the body until they meet a specific target site and attach to surfaces and begin to release the drug in a controlled and predictable manner. Because the drug can be delivered to a specific target site instead of circulating throughout the body, it is more effective for a given specific dose. They are easy to make and safe for biological use. Different types of cyclodextrins can be cross-linked using a carbonyl or a dicarboxylate chemical as a cross-linker to create nanosponges. This groundbreaking technology has been extensively investigated for the delivery of medications for oral, topical, and parental administrations. Vaccines, antibodies, proteins, and enzymes can all be effectively transported via Nanosponges. The current review emphasizes the methods, advantages, disadvantages, characterization, and applications of nanosponges.

Dimethyl-α-cyclodextrin induces capacitation by removing phospholipids from the plasma membrane of mouse sperm†.

Capacitation is an important event in the completion of fertilization by mammalian sperm. Cholesterol efflux is a trigger of capacitation. In general, cholesterol acceptors of albumin and β-cyclodextrins are used to induce capacitation during in vitro fertilization. Previously, we reported that methyl-β-cyclodextrin (MBCD), which is composed of seven glucoses, had a higher ability to induce capacitation than bovine serum albumin (BSA) in frozen-thawed mouse sperm. Comparison of albumin and cyclodextrins is helpful for understanding the mechanism of capacitation. In this study, we examined the effects of albumin, MBCD, and a different type of cyclodextrin, dimethyl-α-cyclodextrin (DMACD), which is composed of six glucoses, on several events of sperm capacitation. We showed that DMACD induced sperm capacitation and promoted fertilization ability. The time required to increase the fertilization rate differed among BSA, MBCD, and DMACD. BSA and MBCD enhanced cholesterol and phospholipid efflux, whereas DMACD enhanced only phospholipid efflux. BSA, MBCD, and DMACD increased sperm membrane fluidity, rearrangement of the lipid raft, and the acrosome reaction. These findings suggest that phospholipid efflux is a novel trigger of capacitation. Increasing the choice of sperm capacitation inducers may be useful for improving in vitro fertilization (IVF) techniques not only in mice, but also in various species in which it has been difficult to produce embryos by IVF.

Bacterial phototoxicity of lumichrome photocrosslinked collagen hydrogels

In response to the World Health Organization's (WHO) call to develop alternative antibacterial methods, we investigate endogenous compounds and biopolymers. Lumichrome (LC) is an endogenous, lipophilic degradation product of riboflavin (vitamin B2) that can act as a photosensitizer for antimicrobial applications. LC is also a photocrosslinker of collagen. Crosslinked collagen hydrogels were prepared with two types of cyclodextrins (CDs), namely (2-hydroxypropyl)-β-CD (HPβCD) and -γ-CD (HPγCD), to improve the aqueous solubility of LC. The release of LC from the collagen gels and the phototoxic effect of UVA-irradiated LC against planktonic Staphylococcus (S.) aureus were investigated. Irradiation of LC hydrogels complexed with either CD resulted in similar levels of bacterial death despite the HPγCD gels containing half the LC concentration of the HPβCD gels. This effect may be explained by the higher complexation efficiency and stability of the LC-HPβCD complex, slowing down the LC release. Following treatment, small colony variants of S. aureus were observed. The study is a proof of concept of the release and phototoxic effects of an endogenous photocrosslinker embedded in a biopolymer as a sustainable antibacterial alternative to conventional therapy of, e.g., infected wounds.

Insights on macro- and microscopic interactions between Confidor and cyclodextrin-based nanosponges

Imidacloprid is one of the most widely used soluble neonicotinoid insecticide, which is non–volatile and persists in the soil, with hazardous effects on birds, honeybees, and mammals. It is used in both agricultural and veterinary applications, and is found in at least 7% of European topsoils. One of the commercially available formulations is Confidor O–TEQ® that exhibits higher retention, spreading, and penetration capacity being in form of an oil suspension. In this work, porous materials based on cyclodextrin nanosponges (CDNSs) were developed for the efficient removal of imidacloprid. In the synthesis of CDNSs, α– and β–cyclodextrin and two diamine monomers, hexane–1,6–diamine (HDA) and dodecane–1,12–diamine (DDA) were used. It was found that linkers with longer aliphatic chains resulted in CDNSs with higher thermal stability and crosslinking degree. αCD2–HDA and βCD2–HDA showed superior sorption efficiency for Confidor O–TEQ®, as evaluated by kinetic and equilibrium sorption analyses at optimal conditions. To better understand the effects of monomer chain length and type of cyclodextrin, the sorption performance of αCD and βCD, αCD–HDA and βCD–HDA, αCD–DDA and βCD–DDA, dimeric αCD2–HDA and βCD2–HDA, and αCD2–DDA and βCD2–DDA with imidacloprid was also investigated by atomistic molecular dynamics simulations. Relevant contact patterns based on the identification of the stabilizing/destabilizing noncovalent interactions within the CD-based complexes were described in detail. Results suggest that significant modulation of the sorption performance of CDNSs for imidacloprid can be achieved by imposing various features, with direct implications for the rational design of supramolecular materials with high sorption capacity for pesticides.

Improvement of chemo- and stereoselectivity for phosphorothioate oligonucleotides in capillary electrophoresis by addition of cyclodextrins

Phosphorothioate (PS) modification is one of the most widely used oligonucleotide chemical alterations in the oligonucleotide backbone. It has proven to be crucial in the field of therapeutic oligonucleotides regarding the optimization of their physicochemical and biological properties. In this study, a capillary electrophoresis (CE) method with an acidic background electrolyte (BGE) containing a combination of β- and γ-cyclodextrins derivatives as chiral selectors is proposed for the diastereomeric separation of 5-mer oligonucleotides containing 0, 1, 2, or 3 phosphorothioate linkages (5´-TCGTG-3´). The effects of the BGE pH, organic modifier addition, and type of cyclodextrin (CD) on chemo- and stereoselectivity and resolution were studied. A mixture of 25 mM (2-hydroxy-3-N,N,N-trimethylamino)propyl-γ-CD and 10 mM carboxymethyl-β-cyclodextrin in a pH 3 buffer was found to be the most appropriate system for the qualitative evaluation of the short oligonucleotides investigated. These phosphorothioate oligonucleotides were separated with high efficiency in less than 11 min with no capillary treatment. The suggested approach can be the basis for purity testing of this new generation of therapeutics.