Cyclodextrins

To explore the use of cyclodextrins (CD) to form inclusion complexes with ␤-lapachone (␤-lap) to overcome solubility and bioavailability problems previously noted with this drug. Methods. Inclusion complexes between ␤-lap and four cyclodextrins (␣-, ␤-, ␥-, and HP␤-CD) in aqueous solution were investigated by phase solubility studies, fluorescence, and 1 H-NMR spectroscopy. Biologic activity and bioavailability of ␤-lap inclusion complexes were investigated by in vitro cytotoxicity studies with MCF-7 cells and by in vivo lethality studies with C57Blk/6 mice (18-20 g).

Cyclodextrins are widely used excipients in pharmaceutical formulations. They are mainly utilized as solubilizers and absorption enhancers, but recent results revealed their effects on cell membranes and pharmacological barriers. In addition to the growing knowledge on their interaction with plasma membranes, it was confirmed that cyclodextrins are able to enter cells by endocytosis. The number of the tested cyclodextrins was limited, and the role of this mechanism in drug absorption and delivery is not known. Our aim was to examine the endocytosis of fluorescently labeled hydroxypropyl-β-cyclodextrin, random methyl-β-cyclodextrin and soluble β-cyclodextrin polymer, and the cellular uptake of the fluorescent paclitaxel derivative-random methyl-β-cyclodextrin complex. The studied cyclodextrin derivatives were able to enter Caco-2 intestinal cells and localized in vesicles in the cytoplasm, while their permeability was very limited through Caco-2 monolayers. We demonstrated for the fi...

Haloperidol (Hal), a highly hydrophobic drug, was complexed with two i-cyclodextrin (i-CD) derivatives. Hal solubility was increased 20-fold in the presence of a 10-fold excess of methyl i-CD (Mei-CD) and 12-fold in the presence of a 10-fold excess of 2-hydroxypropyl i-CD (HPi-CD). The stoichiometries and stability constants of Hal-Mei-CD (1:1 and 2345 M − 1 at 27°C) and Hal -HPi-CD (1:1 and 2112 M − 1 at 27°C) complexes were calculated by the continuous variation and phase solubility methods respectively. Differential scanning calorimetry and 1 H-NMR were used to confirm the formation of inclusion complexes. Moreover, the enthalpy and entropy of the complexation process were calculated for both complexes in order to obtain such information as the main 'driving force' and whether or not complex formation is thermodynamically favoured. This was achieved by monitoring the isothermic solubility lines at various temperatures. © 1997 Elsevier Science B.V.

Solubilization of hydrophobic drugs at the molecular level as inclusion complexes inside cyclodextrins (CDs) offers a good alternative for improving their stability, solubility and bioavailability, and for preventing against their possible toxicity or controlling secondary effects. Therefore CDs are widely used as solubilizing excipients. However since dissociation takes place too readily upon dilution, inclusion complexes inside simple water-soluble CD appears ineffective for drug delivery applications. Chemical modifications of CDs allow them to self-organize as larger assemblies useful for resolving this lability issue. Depending on the position, the number and the nature of these groups, amphiphilic CDs can form assemblies such as vesicles, solid-lipid nanoparticles, nanospheres, liquid crystals, or micellar systems. This review deals with the synthesis of amphiphilic cyclodextrins leading to supramolecular assemblies and the physical properties of these assemblies. From the fir...

Résumé Le mitotane (o,p -dichlorodiméthyl dichloroéthane [o,p -DDD]) est utilisé dans le traitement du cancer de la corticosurrénale et parfois chez des patients atteints du syndrome de Cushing. Ce principe actif est très peu soluble dans l'eau et, après administration orale, environ 60 % de la dose initiale est retrouvée dans les selles. La préparation d'une forme soluble pourrait permettre d'améliorer la biodisponibilité. La caractérisation d'un complexe soluble à base de cyclodextrines constitue l'objectif de ce travail. L'inclusion de mitotane dans la méthyl-ß-cyclodextrine a été étudiée en réalisant des diagrammes de solubilité de phase et des expériences de RMN. Pour déterminer le mécanisme d'inclusion, l'o,p -DDD a été comparé à son régioisomère, le p,p -DDD. Nous avons démontré que deux diméthyl-ß-cyclodextrines (DMßCD) peuvent complexer les cycles aromatiques. À partir des diagrammes de solubilité de phase, on observe également que les deux complexations sont très différentes. K 1:1 est compris entre 37 000 et 85 000 mol.l −1 alors que K 1:2 est compris entre 5,3 et 32 mol.l −1 . Les expériences de RMN ont confirmé l'inclusion et ont permis d'obtenir des indications sur la cinétique de dissociation : la partie ortho-chloro subit un équilibre lent comparativement à l'échelle de temps de la RMN, tandis que la partie para-chloro subit un échange rapide.

In the development of new antibacterial therapeutic approaches to fight multidrug-resistant bacteria, antimicrobial photodynamic therapy (aPDT) represents a well-known alternative to treat local infections caused by different microorganisms. Here we present a polypropylene (PP) fabric finished with citrate-hydroxypropyl-βCD polymer (PP-CD) entrapping the tetra-anionic 5,10,15,20-tetrakis(4-sulfonatophenyl)-21H,23H-porphine (TPPS) as photosensitizer eluting scaffold (PP-CD/TPPS) for aPDT. The concept is based on host-guest complexation of porphyrin in the cavities of CDs immobilized on the PP fibers, followed by its sustained and controlled delivery in release medium and simultaneous photo-inactivation of microorganisms. Morphology of fabric was characterized by optical (OM) and scanning electron microscopies (SEM). Optical properties were investigated by UV-vis absorption, steady- and time-resolved fluorescence emission spectroscopy. X-ray Photoelectron Spectroscopy (XPS) and FT-IR ...

Four different poly(pyridine) complexes of ruthenium, viz. Ru II (trpy)(phen)(OH 2 )] 2+ (1), trans-[Ru III (2,2'bpy) 2 (OH 2 )(OH)] 2+ (2), [(2,2'bpy) 2 (OH)Ru II-I ORu III (OH)(2,2'bpy) 2 ] 4+ (3), and [Ru II (4,4'bpy)(NH 3 ) 5 ] 2+ (4) (2,2'bpy=2,2'-bipyridine, 4,4'bpy=4,4'-bipyridine, trpy= 2,2',2''-terpyridine, phen=1,10-phenanthroline), were tested as non-physiological charge mediators of 'second-generation' glucose biosensors. The membranes for these biosensors were prepared by casting anionic carboxymethylated β-cyclodextrin polymer films (β-CDPA) directly onto the Pt or glassy carbon (GC) disk electrodes. Simultaneously, glucose oxidase (GOD) was immobilized in the films by covalent bonding and the Ru complexes were incorporated both by inclusion in the β-CD molecular cavities and by ion exchange at the fixed carboxymethyl cation-exchange sites. The leakage of the mediator from the polymer has been minimized by adopting a suitable pre-treatment procedure. The biosensors catalytic activities increased in the order 1<2<3<4, as established by linear sweep voltammetry. In case of complexes 2-4, the enzymatic glucose oxidation was mediated by the Ru complexes at their redox potentials. However, this oxidation was mediated by oxygen in case of complex 1 where H 2 O 2 was detected as the reaction product. The effectiveness of the mediators used in the presence of oxygen has been estimated using Pt and GC supports. The redox potential of the mediator does not depend on the support used, while the oxidation of H 2 O 2 proceeds on GC at much higher positive potentials than on Pt. The sensitivity and the linear concentration range of the biosensor studied varied significantly. For complex 4, which forms stable inclusion complex with β-CD, the biosensor sensitivity was the highest and equal to 7.2 µA mM -1 cm -2 , detectability was as low as 1 mM, but the linear concentration range was limited only to 4 mM. In contrast, for complexes 2 and 3 the sensitivity was 0.4 and 3.2 µA mM -1 cm -2 , while the linear concentration range extended up to at least 24 and 14 mM glucose, respectively. Even though some common interfering substances, such as ascorbate, paracetamol or urea, are oxidized at potentials close to those of the Ru complex redox couples, their electro-oxidation currents at physiological concentrations are insignificant compared to those due to the biocatalytic oxidation of glucose. The biosensor response to glucose is reversible as demonstrated by the inhibition of GOD activity by Cu(II). That is, the Cu(II) concentration required to inhibit by half the response to glucose of the biosensor containing complex 2 was 1.0 mM. This inhibitory effect was fully reversed by addition of citrate, a ligand forming sufficiently stable complex with Cu(II).

The design of functional cyclodextrin (CD) nanoparticles is a developing area in the field of nanomedicine. CDs can not only help in the formation of drug carriers but also increase the local concentration of drugs at the site of action. CD monomers form aggregates by self-assembly, a tendency that increases upon formation of inclusion complexes with lipophilic drugs. However, the stability of such aggregates is not sufficient for parenteral administration. In this review CD polymers and CD containing nanoparticles are categorized, with focus on self-assembled CD nanoparticles. It is described how the nanoparticles can be stabilized and tuned to have specific properties.

S ynthetic polymers, typically prepared by addition polymerization or stepwise polymerization, are used constantly in our daily lives. In recent years, polymer scientists have focused on more environmentally friendly synthetic methods such as mild reaction conditions and biodegradable condensation polymers, including polyesters and polyamides. However, challenges remain in finding greener methods for the synthesis of polymers. Although reactions carried out in water are more environmentally friendly than those in organic solvents, aqueous media can lead to the hydrolysis of condensation polymers. Furthermore, bulk polymerizations are difficult to control.

A simple and effective technique of improving delivery of hydrophobic drugs from swellable systems is presented. Conventional methods of drug loading in hydrogel systems are limited by the characteristics of the pharmacological agent. The approach we present uses complexants to modulate drug release. Crosslinked poly(ethylene glycol) (PEG) hydrogels were synthesized, characterized, and used for vascular applications. The release of cyclosporine (CyA) from PEG hydrogels is significantly altered by the sterilization techniques. It was hypothesized that the release of CyA from PEG hydrogels can be modulated by using complexants. A cyclodextrin–CyA complex solution was prepared and used for drug loading. The sterilized PEG hydrogels that were loaded using the cyclodextrin–CyA complex solution had favorable release characteristics compared with the release from PEG hydrogels that were loaded using the conventional technique. Hence, drug release from swellable systems can be tailored by the application of this strategy. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2005

Cyclodextrins (CDs) are a family of cyclic oligosaccharides composed of a-(1,4)-linked glucopyranose subunits. The most important feature of CDs is their ability to form inclusion complexes (host-guest complexes) with a very wide range of solid, liquid and gaseous compounds by a molecular complexation. During the last decade, a considerable number of research papers has been focused on the use of CDs to enhance fluorescence intensity of different analytes and to develop CD-induced spectrofluorimetric method. In this review, the various spectrofluorimetric methods based on host-inclusion complex are presented.

Although technological innovations in the area of drug delivery claim for varied benefits, increasing the drug therapeutic index for human clinical application is the main goal pursued. Drug delivery systems for local anesthetics (LA) have attracted researchers due to many biomedical advantages associated to their application. Formulation approaches to systemically deliver LA include the encapsulation in liposomes, complexation in cyclodextrins, association with biopolymers and others carrier systems. Topical delivery systems for LA are characteristically composed by a diversity of adjuvants (viscosity inducing agents, preservatives, permeation enhancers, emollients,…) and presentations such as semisolid (gel, creams, ointments), liquid (o/w and w/o emulsions, dispersions) and solid (patches) pharmaceutical forms. The proposed formulations aim to reduce the LA concentration used, increase its permeability and absorption, keep the LA at the target site for longer periods prolonging the anesthetic or analgesic effect and, finally, to decrease the clearance, local and systemic toxicity. This review deals with the innovations pertaining to formulations and techniques for drug delivery of topical and injectable local anesthetics, as described in recent patents.

Simultaneous chiral separation of 3,4-methylenedioxymethamphetamine (M D MA), 3-4-me thylenedioxyamphetamine (M DA), 3,4-methylenedioxyethylamphetamine (MDE), ephedrine, amphetamine and methamphetamine by capillary electrophoresis in uncoated and coated capillaries with native P-cyclodextrin as the chiral selector: Preliminary application to the analysis of urine and hair The importance of the chiral analysis of amphetamine-related substances in both clandestine preparations and biological samples is widely recognized. For this purpose, capillary electrophoresis was successfully applied by several authors, but only few reports concerned ring-substituted amphetamines, which represent the main components of "ecstasy", a widely abused "recreational" substance. In the present work, the simultaneous chiral analysis of ephedrine, amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA), 3-4-methylenedioxyamphetamine (MDA) and 3,4-methalenedioxyethylamphetamine (MDE) is reported, by using capillary electrophoresis with native P-cyclodextrin (15 mM) as the chiral selector. After preliminary tests at different pH values (phosphate buffer 100 mM, pH 2.5-9.0) and with bare or coated fused-silica capillaries, the optimized conditions were: pH 2.5 phosphate, uncoated capillary (45 cm X 50 pm inner diameter), potential 10 kV. Detection was either by fixed wavelength (200 nm) or multiwavelength (190-400 nm) UV absorbance. Under these conditions, good resolution was obtained for all the analytes, with excellent chiral selectivity and efficiency. The sensitivity for the individual enantiomers was better than 0.2 pg/mL, analytical precision was characterized by relative standard deviation values < 0.8 Yo (5 0.15% with internal standardization) for migration times intra-day and < 2.0% (< 0.54% with internal standardization) day-today ; linearity, in the range 0.156-40 pg/mL, and accuracy were also satisfactory. After a simple liquid-liquid extraction, urine samples could be analyzed with a sensitivity well below the recommended NIDA cutoff of 500 ng/mL. For hair samples, it was necessary to increase the sensitivity by applying a field-amplified sample stacking procedure, which allowed the chiral determination of MDA, MDMA and MDE at concentrations occurring in real samples from ecstasy users, with the possibility of recording UV spectra of the peaks.

Clopidogrel bisulphate, an anti-platelet drug, has been separated from its impurities, namely impurity A, B and C by capillary zone electrophoresis (CZE) using uncoated fused-silica capillary (50.0 m internal diameter, 31.2 cm total length). Four factors affected the separation: buffer concentration, pH of the buffer, concentration of the chiral selector and the applied voltage. Optimization and robustness studies were performed with the aid of reduced central composite experimental design. The buffer used was triethylamine-phosphoric acid and the chosen chiral selector was sulphated ␤-cyclodextrin (SCD). The best separation was achieved by using 10 mM buffer, pH 2.3, containing 5% (mass/volume (m/v)) SCD. Reversed polarity mode was used with an applied voltage of −12 kV and the capillary temperature was maintained at 20 • C. The method was validated for quantitative determination of the drug. It offered a limit of detection (LOD) of 0.13 g/ml, a limit of quantitation (LOQ) of 0.4 g/ml, and a linearity range of 0.4-300 g/ml. Commercial bulk samples were analyzed using the developed method.

Egg yolk is common functional ingredient in food production, mainly in mayonnaise as an emulsifier. Egg yolk cholesterol was removed using β-cyclodextrine, treated with α-amylase, and low-cholesterol mayonnaise produced. The flow behavior of cholesterol-reduced mayonnaise was investigated at different cholesterol-reduced egg yolk and xanthan gum content. The aim of this study was to evaluate the effects of different formulations at various percentages of egg yolk (EY; 4 and 6 percent by weight) and xanthan gum (XG; 0.5 and 0.7 percent by weight) on flow behavior and physicochemical properties of reduced-fat and low-cholesterol mayonnaise prepared with cholesterol-reduced liquid egg yolk and to obtain suitable model for mayonnaise formulations. The aim of the study was to develop a reduced-fat and lowcholesterol mayonnaise with properties similar to those of typical mayonnaise in the market. For this purpose, four reduced-fat and low-cholesterol mayonnaise formulations were prepared in the laboratory using cholesterol-reduced EY. They were compared with a commercial mayonnaise from a local market as a control sample. According to results, color parameters and flow behaviors of the samples compared with the control sample indicated that the samples had higher values of lightness and yellowness, and presented lower values of yield stress and flow behavior index and higher values of consistency coefficient with respect to the commercial product, except recipe that included 6% of EY and 0.7% of XG, which exhibited similar values to the typical commercial one in the market. The Herschel Bulkley model was employed in order to evaluate the effect of EY and XG ratios on mayonnaise rheological behavior. In general, the results obtained suggest that the recipe with EY (6 wt%) and XG (0.7 wt%) had better rheological characteristics and physicochemical properties those prepared with various formulations, maintaining the reduced-fat and low-cholesterol mayonnaise prepared with βcyclodextrine-treated cholesterol-reduced EY. It can be interpreted that the developed product may have potential use in industrial application.

Cyclodextrins are cyclic oligosaccharides with a hydrophilic outer surface and a somewhat lipophilic central cavity. Cyclodextrins are able to form water-soluble inclusion complexes with many lipophilic water-insoluble drugs. In aqueous solutions drug molecules located in the central cavity are in a dynamic equilibrium with free drug molecules. Furthermore, lipophilic molecules in the aqueous complexation media will compete with each other for a space in the cavity. Due to their size and hydrophilicity only insignificant amounts of cyclodextrins and drug/cyclodextrin complexes are able to penetrate into lipophilic biological barriers, such as intact skin. In general, cyclodextrins enhance topical drug delivery by increasing the drug availability at the barrier surface. At the surface the drug molecules partition from the cyclodextrin cavity into the lipophilic barrier. Thus, drug delivery from aqueous cyclodextrin solutions is both diffusion controlled and membrane controlled. It appears that cyclodextrins can only enhance topical drug delivery in the presence of water.

In this study, progesterone, a neutral hydrophobic compound, was selected as a model compound. The goal of the project was to test the hypothesis that PEG-400 and CD may have a synergistic effect on the solubility of progesterone. Captisol ® (hepta sulfobutyl ether) and Trappsol ® HPB (hydroxypropyl beta CD) were used as 2 different types of CDs. Captisol possesses a negative charge, whereas Trappsol HPB is uncharged. The effect of polysorbate 80 on the synergism of PEG-CD in solubilization of the model compound also was examined.

An implantable, anti-microbial delivery device for the treatment of periodontal disease has been developed. In this polymer-based delivery system, the encapsulation efficiency, release characteristics, and bioactivity of anti-microbial agent were controlled by the complexation of the drug with cyclodextrins of differing lipophilicity. Microparticles of poly(dl-lactic-co-glycolic acid) (PLGA) containing chlorhexidine (Chx) free base, chlorhexidine digluconate (Chx-Dg) and their association or inclusion complex with methylated-b-cyclodextrin (MBCD) and hydroxypropyl-b-cyclodextrin (HPBCD) were prepared by single emulsion, solvent evaporation technique. It was observed that encapsulation efficiency and release of the chlorhexidine derivatives from the microparticles was a function of the lipophilicity of the cyclodextrin. Complexation of the poorly water soluble Chx with the more hydrophilic HPBCD resulted in 62% higher encapsulation efficiency and longer duration of sustained release over a 2-week period than complexation with the more lipophilic MBCD. In contrast, the complexation of the more water-soluble derivative of chlorhexidine, Chx-Dg, with the more lipophilic MBCD improved encapsulation efficiency by 12% and prolonged its release in comparison to both the free Chx-Dg and its complex with HPBCD. Furthermore, it was observed that the initial burst effect could be diminished by complexation with CD. Preliminary studies have shown that the chlorhexidine released from PLGA chips is biologically active against bacterial population that is relevant in periodontitis (P. gingivalis and B. forsythus) and a healthy inhibition zone is maintained in agar plate assay over a period of at least a 1-week. The PLGA/CD delivery system described in this paper may prove useful for the localized delivery of chlorhexidine salts and other anti-microbial agents in the treatment of periodontal disease where prolonged-controlled delivery is desired. r

Rectal drug delivery is an efficient alternate to oral and parenteral route of administration in partial avoidance of first pass metabolism and protein peptide drug delivery. This route allows both local and systemic therapy of drugs. Controlled absorption enhancement of drugs can be achieved by the rectal route because of the constant conditions in the rectal environment. In the present review various absorption enhancers with their mechanism of action in improving drug absorption through rectal epithelium and the potential of rectal route in delivering protein and peptides, analgesics and antiepileptics are discussed. This review also presents affects of various absorption promoting adjuvant on the rectal absorption of drugs.

Efficient drug delivery to the eye remains a challenging task for pharmaceutical scientists. Due to the various anatomical barriers and the clearance mechanisms prevailing in the eye, conventional drug delivery systems, such as eye drop solutions, suffer from low bioavailability. More invasive methods, such as intravitreal injections and implants, cause adverse effects in the eye. Recently, an increasing number of scientists have turned to nanomaterialbased drug delivery systems to address the challenges faced by conventional methods. This paper highlights recent applications of various nanomaterials, such as polymeric micelles, hydrogels, liposomes, niosomes, dendrimers, and cyclodextrins as ocular drug delivery systems to enhance the bioavailability of ocular therapeutic agents.

The purpose of this review is to discuss and summarize some of the interesting findings and applications of cyclo-dextrins (CDs) and their derivatives in different areas of drug delivery, particularly in protein and peptide drug delivery and gene delivery. The article highlights important ...

Cyclodextrins have gained currency as useful solubilizing excipients with an ever increasing list of beneficial properties and functionalities. Although their use in liquid dosage forms including oral and parenteral solutions is straightforward, their application to solids can be confounded by the added bulk that is contributed to the formulation. This factor has limited the use of cyclodextrin in tablets and relates systems mainly to potent drug substances. Increasing the ability of cyclodextrins to complex with drug through a manipulation of their complexation efficiency (CE) may expand the use of these materials to the increasing list of drug candidates and marketed drugs who may benefit from this technology. This brief review assesses tools and materials that have been suggested for increasing the CE for pharmaceutically useful cyclodextrins and drugs. The relative importance of impacting the drug solubility (S 0 ) and phase-solubility isotherm slope is discussed in the context of drug ionization and salt use; the impact of polymers, charge interactions, and charge shielding; and the coincidental formation of other complex types in the media. The influence of drug form as well as supersaturation is also discussed in the context of the responsible mechanisms along with aggregation, inclusion, and noninclusion complex formation.

Hydrophilic nanogels combine the advantages of hydrogels with certain advantages that are inherent in their nanoscale size. Similar to macrogels, nanogels can contain and protect drugs and regulate their release by incorporating high-affinity functional groups, stimuli-responsive conformations and biodegradable bonds into the polymer network. Similar to nanoparticles, nanogels can easily be administered in liquid form for parenteral drug delivery. The nanoscale size of nanogels gives them a high specific surface area that is available for further bioconjugation of active targeting agents. Biodistribution and drug release can be modulated through size adjustments. The incorporation of hydrophilic cyclodextrin (CD) moieties into the polymeric network of the nanogels provides them with a drug loading and release mechanism that is based on the formation of inclusion complexes without decreasing the hydrophilicity of the network. The covalent attachment of CD molecules to the chemically crosslinked networks may enable the CDs to display fully their ability to form complexes, while simultaneously preventing drug release upon media dilution. The preparation, characterization and advantages for pharmaceutical and biomedical applications of CD-based nanogels are reviewed in this article.

The bitter taste of drugs, food components, and any other substances which get in the mouth as dissolved in an aqueous solution, or in the saliva, can be strongly reduced or fully eliminated, if the bitter component forms an inclusion complex with an appropriate cyclodextrin (CD). The value of the complex association constant (determined by the structure of the bitter 'guest' molecule and the size and eventual substitution of the 'host' CD molecule), the temperature and the host/guest ratio determine the extent of complexation of the guest molecule (percentage of complexation) at the equilibrium. The K ass for most drug/CD complexes at 36 8C buccal cavity temperature is between 10 2 and 10 4 mol K1 . If the unit dose (of a sublingual or chewing tablet, chewing gum) with a bitter drug (molecular weight of about 150, forming a 1:1 complex with bCD) is approximately 10 mg then the bCD can be taken in a 5-or even 10-fold molar excess. Under such conditions more than 99% of the bitter drug is complexed, and because complexed molecules cannot react with the taste buds in the buccal cavity no bitter taste is perceived. Frequently, preparation of the drug/CD complex is not necessary, because the bCD is present in a large excess, dissolved very quickly in the saliva and results in a saturated CD solution. Therefore, the complexation of the bitter drug is completed very rapidly. Only dissolved substances have taste and only CD complexable drug molecules can become debittered by CDs. Bitter, astringent components of foods (e.g. soya), beverages (e.g. naringin in citrus fruit juice, or chlorogenic acid and polyphenols in coffee) cigarette smoke (nicotine) also can be complexed and their taste reduced or fully eliminated. q

Due to their unique structural, physical and chemical properties, cyclodextrins and their derivatives have been of great interest to scientists and researchers in both academia and industry for over a century. Many of the industrial applications of cyclodextrins have arisen from their ability to encapsulate, either partially or fully, other molecules, especially organic compounds. Cyclodextrins are non-toxic oligopolymers of glucose that help to increase the solubility of organic compounds with poor aqueous solubility, can mask odors from foul-smelling compounds, and have been widely studied in the area of drug delivery. In this review, we explore the structural and chemical properties of cyclodextrins that give rise to this encapsulation (i.e., the formation of inclusion complexes) ability. This review is unique from others written on this subject because it provides powerful insights into factors that affect cyclodextrin encapsulation. It also examines these insights in great detail. Later, we provide an overview of some industrial applications of cyclodextrins, while emphasizing the role of encapsulation in these applications. We strongly believe that cyclodextrins will continue to garner interest from scientists for many years to come, and that novel applications of cyclodextrins have yet to be discovered.

Biological barriers are the main defense systems of the homeostasis of the organism and protected organs. The bloodebrain barrier (BBB), formed by the endothelial cells of brain capillaries, not only provides nutrients and protection to the central nervous system but also restricts the entry of drugs, emphasizing its importance in the treatment of neurological diseases. Cyclodextrins are increasingly used in human pharmacotherapy. Due to their favorable profile to form hydrophilic inclusion complexes with poorly soluble active pharmaceutical ingredients, they are present as excipients in many marketed drugs. Application of cyclodextrins is widespread in formulations for oral, parenteral, nasal, pulmonary, and skin delivery of drugs. Experimental and clinical data suggest that cyclodextrins can be used not only as excipients for centrally acting marketed drugs like antiepileptics, but also as active pharmaceutical ingredients to treat neurological diseases. Hydroxypropyl-b-cyclodextrin received orphan drug designation for the treatment of Niemann-Pick type C disease. In addition to this rare lysosomal storage disease with neurological symptoms, experimental research revealed the potential therapeutic use of cyclodextrins and cyclodextrin nanoparticles in neurodegenerative diseases, stroke, neuroinfections and brain tumors. In this context, the biological effects of cyclodextrins, their interaction with plasma membranes and extraction of different lipids are highly relevant at the level of the BBB. Ó 2014 IMSS. Published by Elsevier Inc.

This paper reports the application of a dehydrogenase enzyme mimic as a biomimetic sensor. The model compound investigated was a b-cyclodextrin (b-CD) derivative with a nicotinamide group attached to the secondary face of a b-CD . It was envisaged that the nicotinamide group would act as the electron transfer agent and that the cyclodextrin would provide a suitable hydrophobic cavity for the reaction to take place in. Ethanol, propranalol, dopamine and acetone were used as substrates in backgrounds of hydrophilic and hydrophobic anions. Electrochemical and fluorescence techniques were used to study the catalytic effects in solution. It was found that the size of the analyte and the hydrophobicity of the anion affected the catalytic activity of the dehydrogenase mimic. Catalytic effects were most enhanced with ethanol and dopamine in presence of larger and more strongly solvated anions, SO 4 2( and H 2 PO 4 ( which are excluded from the cavity. The molecule was also immobilised in a sol Á/gel matrix and investigated as a sol Á/gel electrochemical biomimetic sensor. Concentration dependence with increasing aliquots of ethanol was observed. These results indicated that a re-usable biomimetic sensor is indeed feasible. #

Interaction of piroxicam (PX) and hydroxypropyl-␤-cyclodextrin (HP␤CD) was investigated in solution and in the solid state. Solubility studies demonstrated the formation of the PX-HP␤CD inclusion complex with 1:1 stoichiometry. Equimolecular PX-HP␤CD solid systems were prepared and characterized by differential scanning calorimetry, Fourier transform infrared spectroscopy, and X-ray diffractometry. Modification of the release of a sparingly water-soluble drug, PX, from hydrophilic matrices using cyclodextrin complexation was evaluated. The buccoadhesive controlled release tablets for the delivery of PX were prepared by direct compression of hydroxypropylmethyl cellulose (HPMC) and Carbopol 940 (C940), which showed superior bioadhesion properties compared to HPMC. The tablets were evaluated for their dissolution, swelling and mucoadhesive properties. The in vitro release results demonstrated that matrix tablets containing the PX-HP␤CD solid complex displayed faster PX release compared to those containing a physical mixture or "free" drug. Differences in release rates of PX from the tablets could be attributed to the presence of the polymers and to cyclodextrin complexation. The effect of the polymers on PX release can affect the drug solubility (complexation) and polymer water uptake (swelling). Higher polymer water uptake may result in higher drug solubility and diffusivity in a hydrated polymeric environment. Drug complexation affected also its diffusivity through the semipermeable membrane.

To evaluate the phase solubility curve profile, stability constant (K1:1) and the complexation efficiency (CE) of Progesterone, a BCS class II compound by complexation with three ß-cyclodextrins derivatives: hydroxypropyl-ß-cyclodextrin (Kleptose® HPB, with MS=0.65), hydroxypropyl-ß-cyclodextrin (Kleptose® HP, with MS=0.9) and methylated ß-cyclodextrin (Crysmeb, with MS=0.57). To evaluate the complex formation and stability of liquid and lyophilized complex.

Affinity-based drug delivery systems utilize interactions between the therapeutic drug and the delivery system to manipulate drug loading and to control drug release. In this paper, affinity-based drug delivery system syntheses, types of therapeutic factors delivered, and delivery system loading and release are discussed in detail. The paper is divided into three subsections, based on the type of delivery system: molecular imprinting systems, growth-factor delivery, and cyclodextrin-based delivery. The objective of this paper is to examine the current state of research, highlight the breakthroughs and challenges, point out potential impacts of this relatively new technology, and explore future developmental areas.

The objectives of the reviews are the collection, concise description, comparison and evaluation of the various chromatographic technologies using natural and modified cyclodextrins for the increase the seperation capacity of various chromatographic separation systems.

The objectives of the reviews are the collection, concise description, comparison and evaluation of the various chromatographic technologies except liquid chromatography using natural and modified cyclodextrins for the increase the seperation capacity of various chromatographic separation systems.

Due to their low cytotoxicity, controllable size, and unique architecture, cyclodextrin (CD)-based polyrotaxanes and polypseudorotaxanes have inspired interesting exploitation as novel biomaterials. This review will update the recent progress in the studies on the structures of polyrotaxanes and polypseudorotaxanes based on different CDs and polymers, followed by summarizing their potential applications in life science and biotechnology, such as drug delivery, gene delivery, and tissue engineering. CD-based biodegradable polypseudorotaxane hydrogels could be used as promising injectable drug delivery systems for sustained and controlled drug release. Polyrotaxanes with drug or ligand-conjugated CDs threaded on polymer chain with biodegradable end group could be useful for controlled and multivalent targeting delivery. Cationic polyrotaxanes consisting of multiple oligoethylenimine-grafted CDs threaded on a block copolymer chain were attractive non-viral gene carries due to the strong DNA-binding ability, low cytotoxicity, and high gene transfection efficiency. Cytocleavable end caps were also introduced in the polyrotaxane systems in order to ensure efficient endosomal escape for intracellular trafficking of DNA. Finally, hydrolyzable polyrotaxane hydrogels with cross-linked α-CDs could be a desirable scaffold for cartilage and bone tissue engineering.

In a systematic study of molecular recognition of amino acid derivatives in solid-state ␤-cyclodextrin (␤-CD) complexes, we have determined crystal structures for complexes of ␤-cyclodextrin͞Nacetyl-L-phenylalanine at 298 and 20 K and for N-acetyl-D-phenylalanine at 298 K. The crystal structures for the N-acetyl-L-phenylalanine complex present disordered inclusion complexes for which the distribution of guest molecules at room temperature is not resolvable; however, they can be located with considerable confidence at low temperature. In contrast, the complex with N-acetyl-D-phenylalanine is well ordered at room temperature. The latter complex presents an example of a complex in this series in which a water molecule is included deeply in the hydrophobic torus of the extended dimer host. In an effort to understand the mechanisms of molecular recognition giving rise to the dramatic differences in crystallographic order in these crystal structures, we have examined the intermolecular interactions in detail and have examined insertion of the enantiomer of the D-complex into the chiral ␤-CD complex crystal lattice.