Alpha-cyclodextrin Research Articles

ESI-IM-MS characterization of cyclodextrin complexes and their chemically cross-linked alpha (α-), beta (β-) and gamma (γ-) cyclodextrin particles as promising drug delivery materials with improved bioavailability.

Cyclodextrins (CDs) are natural cyclic oligosaccharides with a relatively hydrophobic cavity and a hydrophilic outer surface. In this study, alpha (α-), beta (β-) and gamma (γ-) CD particles were prepared by directly using α-, β-, and γ-CDs as monomeric units and divinyl sulfone (DVS) as a crosslinker in a single-step via reverse micelle microemulsion crosslinking technique. Particles of p(α-CD), p(β-CD), and p(γ-CD) were perfectly spherical in sub- 10µm size ranges. The prepared p(CD) particles at 1.0mg/mL concentrations were found biocompatible with >95 % cell viability against L929 fibroblasts. Furthermore, p(α-CD) and p(β-CD) particles were found non-hemolytic with <2 % hemolysis ratios, whereas p(γ-CD) particles were found to be slightly hemolytic with its 2.1±0.4 % hemolysis ratio at 1.0mg/mL concentration. Furthermore, a toxic compound, Bisphenol A (BPA) and a highly antioxidant polyphenol, curcumin (CUR) complexation with α-, β-, and γ-CD molecules was investigated via Electrospray-Ion Mobility-Mass Spectrometry (ESI-IM-MS) and tandem mass spectrometry (MS/MS) analysis. It was determined that the most stable noncovalent complex was in the case of β-CD, but the complex stoichiometry was changed by the hydrophobic nature of the guest molecules. In addition, BPA and CUR were separately loaded into prepared p(CD) particles as active agents. The drug loading and release studies showed that p(CD) particles possess governable loading and releasing profiles.

Mechanochemically Scaled-Up Alpha Cyclodextrin Nanosponges: Their Safety and Effectiveness as Ethylene Scavenger.

Aiming at the development of a greener ethylene removal alternative, the goal of this study was to scale up and ensure the safety of α-cyclodextrin nanosponges (α-CD-NS) for further use as ethylene scavengers. The solvent-free synthesis of α-CD-NS was successfully scaled up using α-cyclodextrin and N,N′-carbonyldiimidazole as cross-linkers (1:4 molar ratio) by means of mechanical alloying using a PM 100 ball mill by focusing on varying the rotation frequency, as determined by FTIR-ATR, X-ray diffraction, and TGA. α-CD-NS washing optimization was performed in water by monitoring the imidazole concentration in the washing solution through the validation of a fast and sensitive HPLC-DAD method. After 6 h at 40 °C, all imidazole was extracted, allowing a faster and less energy-dependent extraction. α-CD-NS absorbent capacity and porosity were also evaluated through BET isotherms and ethylene absorption experiments using α-CD-NS and commercially available absorbents (zeolite and bentonite) were performed by means of gas chromatography (GC) coupled to a flame ionization detector (FID). With a 93 µL h−1 kgadsorbent−1 ethylene removal capacity, α-CD-NS revealed the best ethylene scavenging activity when compared to the other absorbents, opening the doors for a safer, innovative, and eco-friendlier ethylene removal active packaging.

Transbilayer Coupling of Lipids in Cells Investigated by Imaging Fluorescence Correlation Spectroscopy.

Plasma membranes host numerous receptors, sensors, and ion channels involved in cellular signaling. Phase separation within the plasma membrane has emerged as a key biophysical regulator of signaling reactions in multiple physiological and pathological contexts. There is much evidence that plasma membrane composition supports the coexistence of liquid-ordered (Lo) and liquid-disordered (Ld) phases or domains at physiological conditions. However, this phase/domain separation is nanoscopic and transient in live cells. It has been recently proposed that transbilayer coupling between the inner and outer leaflets of the plasma membrane is driven by their asymmetric lipid distribution and by dynamic cytoskeleton-lipid composites that contribute to the formation and transience of Lo/Ld phase separation in live cells. In this Perspective, we highlight new approaches to investigate how transbilayer coupling may influence phase separation. For quantitative evaluation of the impact of these interactions, we introduce an experimental strategy centered around Imaging Fluorescence Correlation Spectroscopy (ImFCS), which measures membrane diffusion with very high precision. To demonstrate this strategy, we choose two well-established model systems for transbilayer interactions: cross-linking by multivalent antigen of immunoglobulin E bound to receptor FcεRI and cross-linking by cholera toxin B of GM1 gangliosides. We discuss emerging methods to systematically perturb membrane lipid composition, particularly exchange of outer leaflet lipids with exogenous lipids using methyl alpha cyclodextrin. These selective perturbations may be quantitatively evaluated with ImFCS and other high-resolution biophysical tools to discover novel principles of lipid-mediated phase separation in live cells in the context of their pathophysiological relevance.

A combined molecular docking and molecular dynamics simulation approach to probing the host–guest interactions of Ataluren with natural and modified cyclodextrins

ABSTRACT The objective of this study was to apply molecular docking and molecular dynamics (MDs) simulation approaches to investigate the host–guest interactions between natural Cyclodextrins (CDs) (Alpha, Beta and Gamma Cyclodextrins) and some modified CDs (hydroxypropyl, sulfobutylether and randomly substituted methyl Beta Cyclodextrins) with Ataluren as a small molecule drug designed for diseases attributable to a nonsense mutation. Molecular docking results presented that randomly substituted methyl beta Cyclodextrin (RMBCD) has the highest binding affinity and Alpha Cyclodextrin (ACD) has the lowest binding affinity to Ataluren. According to the MDs simulation results, ACD and hydroxypropyl Cyclodextrin have not proper cavity for encapsulation of Ataluren. In contrast, Ataluren was totally included into the Beta Cyclodextrin (BCD), Gamma Cyclodextrin, sulfobutylether Beta Cyclodextrin (SBECD) and RMBCD due to appropriate interior capability. Moreover, MDs results showed that SBECD has the most conformational flexibility and BCD has the most conformational stability during simulation time. The results of this paper may open new paths to use this formulation for further researches in the delivery mechanism of hydrophobic pharmaceutical molecules.

Investigation of non-covalent complex formation between 2-(4-hydroxyphenylazo) benzoic acid and α-Cyclodextrin in solid and solution forms

Benzoic acid and its derivatives molecules have some biological properties such as antifungal and antimicrobial properties and so these molecules have been especially used in drug industry. In this study, complex formation between alpha cyclodextrin which is a good drug delivery system and 2-(4-hydroxyphenylazo) benzoic acid was performed in both aqueous environment and solid state form. 2-(4-hydroxyphenylazo) benzoic acid, alpha cyclodextrin and 2-(4-hydroxyphenylazo) benzoic acid / alpha cyclodextrin complex were characterized with UV–Vis, FT-IR, NMR, TGA and powder XRD. Experimental results are clear that alpha cyclodextrin is good carrier system for 2-(4-hydroxyphenylazo) benzoic acid molecule. In solid form, complex formation was indicated using FT-IR and powder XRD. In solution phase, it has been shown by UV–Vis and NMR that complex formation between alpha cyclodextrin and 2-(4-hydroxyphenylazo) benzoic acid molecule was successfully performed. Moreover, according to TGA results, thermal stability of alpha cyclodextrin /2-(4-hydroxyphenylazo) benzoic acid complex was increased.

Dry Emulsions based on Alpha Cyclodextrin and Vegetable Oils for Buccal Delivery of Lipophilic Drugs

Background: Buccal delivery of drugs can be used as an alternative administration route to conventional oral route avoiding the liver first-pass effect and improving patient compliance. Objective: The goal of this work was to develop dry emulsions for buccal delivery of ketoprofen, used as a lipophilic model drug. The influence of two vegetable oils, olive oil or wheat germ oil, in the presence of α-cyclodextrin and different drying techniques on the dry emulsion properties was evaluated. Methods: Emulsions were prepared by adding olive oil or wheat germ oil to an aqueous solution of α-cyclodextrin and subsequently dried through an oven, freeze-dryer or spray-dryer. Dry emulsions were characterized in terms of yield, encapsulation efficiency, morphology and drug solid-state. In vitro drug release and permeation studies were carried out to evaluate dry emulsion ability to release the drug and to allow its permeation through the esophageal porcine epithelium. Results: The formation of stable and milky emulsion was assured by cyclodextrin ability to interact with oil components obtaining an inclusion complex with amphiphilic property able to act as a surfaceactive agent. The drying process influenced the yield and the encapsulation efficiency, while no significant differences were observed between olive oil and wheat germ oil. Freeze-dried emulsions, selected as the best formulations, resulted in fast release of drug thereby ensuring its permeation across the epithelium. Conclusion: Dry emulsions prepared with a simple and easy method, using natural ingredients and avoiding synthetic surfactants and organic solvents, could be used for buccal delivery of lipophilic drugs.

Functional characteristics of Bambara groundnut starch-catechin complex formed using cyclodextrins as initiators

Bambara groundnut (BGN) starch extracted from BGN flour was modified through complexation methods using alpha and beta cyclodextrin. Complexation methods used included the microwave, co-evaporation and kneading methods. Cyclodextrin (alpha and beta) were used as initiators for grafting catechin to the BGN starch molecule. The functional properties of native and modified BGN starches were assessed. The swelling capacity of BGN starches increased with an increase in temperature. The swelling capacities of BGN starches ranged from 0.36 g/g (BGN starch modified through the co-evaporation method, beta cyclodextrin + catechin) to 4.84 g/g (BGN starch modified through the microwave method, beta cyclodextrin + catechin). Complexation methods significantly reduced the swelling capacity of native BGN starch. Temperatures had a significant (p ≤ 0.05) effect on the swelling capacity of BGN starches. The solubility of BGN starches ranged from 0.61 g/100 g (native BGN starch) to 46.04 g/100 g (BGN starch modified through the kneading method, alpha cyclodextrin); using water as a solvent. The water absorption of native and modified BGN starches ranged from 0.23 to 1.17 g/g, respectively. Starches complexed with β-cyclodextrin showed increased water absorption capacity in comparison to the starches complexed with alpha cyclodextrin. The modification methods had a significant (p ≤ 0.05) effect on the water absorption capacities of BGN starches. There was no significant difference in the oil absorption capacities of BGN starches and they ranged from 1.02 to 1.07 g/g. Pasting properties of BGN starches were assessed using a rapid visco analyser (RVA). The modified starches exhibited lower breakdown, setback, and final viscosities as well as significant increase in gelatinisation temperature compared to the native BGN starch.

Autoassemblies of α-Cyclodextrin and Grafted Polysaccharides: Crystal Structure and Specific Properties of the Platelets.

Cyclodextrins (CDs) are a family of oligosaccharides with a toroid shape, which exhibit a remarkable ability to include guest molecules in their internal cavity, providing a hydrophobic environment for poorly soluble molecules. Recently, new types of inclusions of α CDs with alkyl grafted polysaccharide chains (pullulan, chitosan, dextran, amylopectin, chondroitin sulfate...) have been prepared which are autoassembled into micro- and nanoplatelets. We report in this paper an extensive investigation of platelets with different compositions, including their reversible hydration (thermogravimetric analysis), crystalline structure (powder X-ray diffraction), dimensions and shapes (scanning electron microscopy-field emission gun), thermal properties, solubility, and melting (micro-differential scanning calorimetry). The crystalline platelets exhibit layered structures intercalating the polysaccharide backbones and CD complexes hosting the grafted alkyl chains. The monoclinic symmetry of columnar-type crystals suggests a head-to-tail arrangement of the CDs. The platelets have a preferentially hexagonal shape with sharp edges, variable sizes, and thicknesses and sometimes show incomplete layers (terraces). The crystal parameters change upon dehydration. Melting temperatures of platelets in aqueous solutions exceed 100 °C. Finally, we discuss the potential relation between the platelet structure and applications for mucoadhesive devices.

Nanoparticles assembled via pH-responsive reversible segregation of cyclodextrins in polyrotaxanes.

Supramolecular polymers with monomers bound together by secondary interactions, such as polyrotaxanes (PRXs), consisting of alpha cyclodextrin (αCD) threaded onto poly(ethylene glycol) (PEG), have attracted interest as a result of their ability to overcome physical limitations present in conventional, covalently structured polymers. Herein, we describe the formation of pH-responsive supramolecular assemblies from carboxyethylester bearing αCD and PEG PRXs. These PRXs were formed using PEG of Mw 20 kDa and a threading degree of 28%. Upon charge neutralisation the threaded αCDs co-localise, resulting in aggregation of the PRXs and the formation of a suspension by self-assembly. This process is shown to be reversible and possible via the mobility of CDs along the PEG guest chain. As a result of the inherent properties of PRXs, such as enhanced multivalent interactions and degradation, these responsive supramolecular polymers are expected to be of interest in fields where PRX-based materials have already found application, including paints, self-healing materials, surface coatings, and polymer therapeutics.

High-performance towards removal of toxic hexavalent chromium from aqueous solution using graphene oxide-alpha cyclodextrin-polypyrrole nanocomposites

Graphene oxide (GO) was functionalized with alpha cyclodextrin (αCD) through a covalent bond to form GO-αCD nanocomposites (NC). GO-αCD NC was further modified with polypyrrole (PPY) to afford an advanced GO-αCD-PPY NC for the removal of highly toxic Cr(VI) from water. The prepared GO-αCD-PPY NCs were successfully characterised with AT-FTIR, FE-SEM, HR-TEM, BET and XRD techniques. Adsorption experiments were performed in batch mode to determine optimum conditions that include temperature, pH, concentration of Cr(VI) and contact time. It was deduced from the experiments that the adsorption of Cr(VI) by the GO-αCD-PPY NC is pH and temperature dependent, where optimum adsorption was achieved at pH2 and it increased with increasing temperature. The adsorption kinetics followed the pseudo-second-order model and the adsorption isotherms fitted well to the Langmuir isotherm model with maximum adsorption capacities ranging from 606.06 to 666.67mg/g. Effect of co-existing ions studies revealed that cations and anions had no significant effect on the adsorption of Cr(VI). Desorption studies also illustrated that the NC can be re-used up to 3cycles.

Comparison of Three Molecular Simulation Approaches for Cyclodextrin‐Ibuprofen Complexation

Cyclodextrins are widely used for the solubilisation of poorly soluble drugs in the formulations. However, current cyclodextrin formulation development strongly depends on trial‐and‐error in the laboratory, which is time‐consuming and high cost. The aim of this research was to compare three modeling approaches (Docking, molecular dynamics (MD), and quantum mechanics (QM)) for cyclodextrin/drug complexation. Ibuprofen was used as a model drug. Binding free energy from three simulation methods was calculated as an important parameter to compare with the experimental results. Docking results from AutoDock Vina program showed that the scoring of complexation capability between ibuprofen and cyclodextrins is alpha (α), gamma (γ), beta (β), and HP‐beta‐cyclodextrins, which indicated similar ranking with the results from phase, solubility diagram experiments. MD simulation indicated that ibuprofen could form the stable complexes with β‐, γ‐, and HP‐β‐cyclodextrins, but not for alpha cyclodextrin. Binding free energies from the MD simulation for β‐, γ‐, and HP‐β‐cyclodextrins were −3.67, −0.67, and −3.87 kcal/mol, individually. The enthalpies of QM simulation for β‐, γ‐, and HP‐β‐cyclodextrins were −17.22, −14.75, and −20.28 kcal/mol, respectively. Results from all three modeling approaches showed similar ranking between ibuprofen and four cyclodextrin molecules as the experimental data. However, MD simulation with entropy calculation had the closest value to experimental data for β and HP‐beta‐cyclodextrins. Thus, MD simulation with MM‐PBSA method may be fit to in silico screen for cyclodextrin formulations.

Interaction Study of an Amorphous Solid Dispersion of Cyclosporin A in Poly-Alpha-Cyclodextrin with Model Membranes by (1)H-, (2)H-, (31)P-NMR and Electron Spin Resonance.

The properties of an amorphous solid dispersion of cyclosporine A (ASD) prepared with the copolymer alpha cyclodextrin (POLYA) and cyclosporine A (CYSP) were investigated by 1H-NMR in solution and its membrane interactions were studied by 1H-NMR in small unilamellar vesicles and by 31P 2H NMR in phospholipidic dispersions of DMPC (dimyristoylphosphatidylcholine) in comparison with those of POLYA and CYSP alone. 1H-NMR chemical shift variations showed that CYSP really interacts with POLYA, with possible adduct formation, dispersion in the solid matrix of the POLYA, and also complex formation. A coarse approach to the latter mechanism was tested using the continuous variations method, indicating an apparent 1 : 1 stoichiometry. Calculations gave an apparent association constant of log Ka = 4.5. A study of the interactions with phospholipidic dispersions of DMPC showed that only limited interactions occurred at the polar head group level (31P). Conversely, by comparison with the expected chain rigidification induced by CYSP, POLYA induced an increase in the fluidity of the layer while ASD formation led to these effects almost being overcome at 298 K. At higher temperature, while the effect of CYSP seems to vanish, a resulting global increase in chain fluidity was found in the presence of ASD.

Scientific Opinion on the substantiation of health claims related to alpha cyclodextrin and reduction of post prandial glycaemic responses (ID 2926, further assessment) pursuant to Article 13(1) of Regulation (EC) No 1924/2006

Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies was asked to provide a scientific opinion on a health claim pursuant to Article 13.1 of Regulation (EC) No 1924/2006 in the framework of further assessment related to alpha-cyclodextrin and reduction of post-prandial glycaemic responses. The food constituent that is the subject of the claim, alpha-cyclodextrin, is sufficiently characterised. The claimed effect, reduction of post-prandial glycaemic responses (as long as post-prandial insulinaemic responses are not disproportionally increased), may be a beneficial physiological effect. The proposed target population is individuals who wish to reduce their post-prandial glycaemic responses. In weighing the evidence, the Panel took into account that two intervention studies showed a significant effect of alpha-cyclodextrin added to starch on post-prandial glycaemic responses without disproportionally increasing post prandial insulinaemic responses, that one study on alpha-cyclodextrin added to sucrose did not show an effect on post-prandial glycaemic responses, and that there is some evidence in support of a plausible mechanism by which alpha-cyclodextrin could exert the claimed effect. On the basis of the data presented, the Panel concludes that a cause and effect relationship has been established between the consumption of alpha-cyclodextrin with starch containing meals and reduction of post-prandial glycaemic responses. The Panel considers that in order to obtain the claimed effect, at least 5 g of alpha-cyclodextrin per 50 g of starch should be consumed. The target population is adults who wish to reduce their post-prandial glycaemic responses.

Formulations based on alpha cyclodextrin and soybean oil: an approach to modulate the oral release of lipophilic drugs

The purpose of this work was to investigate the potential of α-cyclodextrin combined to soybean oil-based formulations to modulate the release of a model drug, indomethacin. Dry emulsion, naked and coated beads were prepared from the same initial formulation using the same manufacturing process. Dry emulsion was selected to accelerate drug release while beads coated with α-cyclodextrin were designed to sustain it. Indomethacin-loaded systems were prepared, characterised and evaluated in vitro. Pharmacokinetic studies were performed in fasted and fed rats. The presence of the α-cyclodextrin coat was confirmed by confocal microscopy, and an increase of the mass and diameter of the beads. The layer of α-cyclodextrin improved their resistance in simulated gastro-intestinal fluids. In vitro, the dissolution of indomethacin was slower with coated beads than with emulsion and naked beads. Lipid-based formulations showed an increase of relative bioavailability of IND versus Indocid®. Whatever the formulation, greater and faster release of indomethacin was noticed in sodium taurocholate-rich medium and in fed rats. Compared to naked beads, an increased Cpmax with a shorter Tmax was observed with the emulsion while Tmax and MRT were increased and Cpmax reduced with the coated beads. Interestingly, formulations based on alpha cyclodextrin and soybean oil can modify the release of a lipophilic drug depending on the system formed.

Effect of dietary fibers on fecal fat excretion in overweight and obese humans

The aim of this study was to examine the effects of dietary fibers, alpha‐cyclodextrin (ACD) or water soluble modified cellulose (WSMC), on fecal fat excretion in overweight and obese humans as compared to positive control (orlistat) or negative control (placebo). This was a randomized, controlled, crossover study with three, double‐blind 7‐d treatment periods followed by an open label, 7‐d orlistat period (180 mg/d). ACD (30 g/d), WSMC (6 g/d), or isocaloric placebo drink (35 kcal/355 ml; 2 servings/d) was consumed in the clinic as part of breakfast and dinner. All foods were provided during the treatment periods. Feces collected during the last 4 days of each treatment were analyzed for fecal fat excretion by nuclear magnetic resonance spectroscopy. Repeated measures of analysis of variance were used to compare responses. Among 31 subjects randomized (mean age: 45.3 ± 2.3 years; BMI: 31.0 ± 0.6 kg/m2), 21 were eligible for efficacy evaluation. There were no significant differences between the ACD or WSMC and placebo in total fecal fat excretion (g fecal fat/4‐d), daily fecal fat (g/d) or % fecal fat. Fecal fat excretion was significantly increased during orlistat period vs. 3 other periods. In conclusion, the results of the present study do not provide evidence that either 30 g/d of ACD or 6 g/d of WSMC, delivered in beverage form, increases fecal fat excretion in overweight and obese humans. Funded by Coca‐Cola Company.

Effects of additives on phase transitions of Poloxamer 407/Poloxamer 188 mixture and release property of monoolein cubic phase containing the poloxamers

The gelling temperature of Poloxamer 407/Poloxamer 188 (16%/10%) mixture solution increased with increasing amount of surfactants. Among surfactants tested, the order of effectiveness in increasing the gelling temperature was sodium dodecyl sulfate (SDS) > tween 20 > cetyltrimethylammonium chloride (CTAC). The gelling temperature increased with the increasing concentration of cyclodextrin (CD). The order of effectiveness in increasing the gelling temperature was gamma CD > beta CD > alpha CD. The gelling temperature increased with increasing concentration of alcohols (ethanol and propylene glycol (PG)). On the contrary, dimethyl sulfoxide (DMSO) decreased the gelling temperature of P407/P188 (16%/10%) mixture solution. On the other hand, the gelling temperature decreased upon addition of NaCl but it increased by addition of MgCl 2. With P407/P188-loaded monoolein cubic phase, the degrees of release in 40 hr were about 52% at 25 °C and 37.5% at 47 °C. The suppressed release at 47 °C is possibly because P407/P188 in the water channel of cubic phase is in gel state at the temperature.

Molecular inclusion of butylated hydroxyanisole (BHA) into alpha and beta cyclodextrins

BHA (butylated hydroxyanisole) was complexed with α- and β-cyclodextrins with the objective of characterizing the thermal stability. From phase solubility diagrams, the association constants for the complexes of α-CD:BHA and β-CD:BHA were found as 49.3 and 585 L mol−1, respectively. To increase the thermal stability of BHA, its molecular encapsulation in α-CD and β-CD, was tested using molar ratios of 1:1 and 1:2 (BHA:CD) and the complex preparation techniques of kneading and physical mixture. The products of complexation were characterized by differential scanning calorimetry and thermogravimetry, indicating the formation of a BHA:β-CD complex and showing that the release of the complexed BHA occurs in the temperature range of 280–350 °C, well above the temperature at which BHA sublimates. Dissolution tests have shown that the BHA: β-CD complex produced by kneading has high efficiency of dissolution and partition coefficient experiments demonstrated that the presence of β-CD leads to higher concentration of BHA in the organic phase.

Construction and characterization of phenol-based sensor derived from colloidal chemistry

In this study, three main objectives are sought: (a) construction of the biosensor by incorporation of a “capturing element” (consisting of alpha cyclodextrin on a sol-derived substrate) and a “detecting element” (consisting of 2,6-dichloro-quinonechloroimine and sodium hydroxide as buffer and electrolyte), (b) physical characterization of the sensor using spectroscopy and microscopy, and (c) sensor performance through electrochemical facility. Correspondingly, Raman spectroscopy and UV–vis spectroscopy have been applied as diagnostic tool to analyze guest–host interaction of the sol-derived phenol sensor. The goal of this study is the incorporation of both an electrochemical and colorimetric detecting elements. It is anticipated that this study provides a possibility of use of biosensor for “one chemical” dual-functional detection. We use this bi-functional detector in the identification of phenol. The detector is based upon sol-derived colloidal chemistry to produce detecting and sensing elements in which detection is colorimetric and also electrochemical in nature.

Total parenteral nutrition turbidity and clearing of serum for assay purposes

Parenteral nutrition such as Liposyn III when introduced into patients causes their serum to become milky thereby creating potentially aberrant analyses when such a medium is subjected to spectrophotometric investigation during the time period prior to the metabolic removal of the intravenously injected triglycerides. However, it is possible to alter chemical reagents by the introduction of enzymatic clearing materials, which rapidly through hydrolytic action by lipases convert the offending triglycerides to glycerol and non-esterified fatty acids. The latter as potential soap formers with calcium and magnesium can be sequentially and quickly incorporated into transparent guest–host complexes with alpha cyclodextrin serving as the host, thus removing them as possible secondary sources of turbidity. Representative procedures incorporating the lipase-alpha cyclodextrin constituents into their reagents thus allow rapid clearing of the medium followed by spectrophotometric measurement during the clarified window of reaction without any change in the modified procedure. Additionally and importantly there is no interference from the addition of the clarifying ingredients added to the reagents. Commonly needed high volume tests such as hemoglobin, glucose, calcium, bilirubin, cholesterol and triglycerides are described as examples in which the clarifying processes are included in this novel analytical technology. No changes in the original methodologies are involved and no preliminary treatments are necessary for these important tests in which the interfering light-scattering properties of a sample are eliminated when optical measurement takes place even during the peak levels of parenteral nutrition necessarily introduced into any patient either adult or neonatal. These procedures involving enzymatic degradation of the triglycerides causing the primary turbidity sequenced to guest–host complexation of liberated fatty acids, the potential secondary turbidity, are effective for clarification of serum samples during measurement. This technology holds whether the source of the hypertriglyceridemia is parenteral nutrition or the pathological presence of excessive triglycerides as in diabetes.

Dimeric Complex of Alpha Cyclodextrin with 1,12-Diaminododecane. Comparison with other Alpha Cyclodextrin Dimeric Complexes

The structure of the complex of alpha cyclodextrin (αCD) with 1,12-diaminododecane has been determined at room temperature. The compound crystal- lizes in the monoclinic, space group P21, with α = 14.10(2), b = 16.91(2), c = 24.45(4) Å, β = 97.40(3)° and D c = 1.398 gcm-3 for Z = 2. Refinement based on 5552 observed MoKα reflections with I> 2õI led to a final R = 0.075. The diamine molecules thread through two αCD arranged in a head-to-head fashion thus, forming [3]pseudorotaxanes. The amine nitrogen atoms, protruding from the primary hydroxyl sides of the αCD dimer, hydrogen-bond to primary hydroxyl oxygen atoms of consecutive dimers and prevent stacking of the dimers along channels. A comparison of the structure to other dimeric structures of αCD shows differences with respect to geometry and packing of the dimers.