DOCSLIB.ORG

Cyclodextrin-Based Contrast Agents for Medical Imaging

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Cyclodextrin-Based Contrast Agents for Medical Imaging molecules Review Cyclodextrin-Based Contrast Agents for Medical Imaging Yurii Shepelytskyi 1,2 , Camryn J. Newman 3, Vira Grynko 1,2 , Lauren E. Seveney 4, Brenton DeBoef 4, Francis T. Hane 2,5 and Mitchell S. Albert 2,5,6,* 1 Chemistry and Materials Science Program, Lakehead University, Thunder Bay, ON P7B 5E1, Canada; [email protected] (Y.S.); [email protected] (V.G.) 2 Thunder Bay Regional Health Research Institute, Thunder Bay, ON P7B 6V4, Canada; [email protected] 3 Biology Department, Lakehead University, Thunder Bay, ON P7B 5E1, Canada; [email protected] 4 Chemistry Department, University of Rhode Island, Kingston, RI 02881, USA; [email protected] (L.E.S.); [email protected] (B.D.) 5 Chemistry Department, Lakehead University, Thunder Bay, ON P7B 5E1, Canada 6 Northern Ontario School of Medicine, Thunder Bay, ON P7B 5E1, Canada * Correspondence: [email protected]; Tel.: +1-807-355-9191 Academic Editors: Marina Isidori, Margherita Lavorgna and Rosa Iacovino Received: 30 October 2020; Accepted: 26 November 2020; Published: 27 November 2020 Abstract: Cyclodextrins (CDs) are naturally occurring cyclic oligosaccharides consisting of multiple glucose subunits. CDs are widely used in host–guest chemistry and biochemistry due to their structural advantages, biocompatibility, and ability to form inclusion complexes. Recently, CDs have become of high interest in the field of medical imaging as a potential scaffold for the development of a large variety of the contrast agents suitable for magnetic resonance imaging, ultrasound imaging, photoacoustic imaging, positron emission tomography, single photon emission computed tomography, and computed tomography. The aim of this review is to summarize and highlight the achievements in the field of cyclodextrin-based contrast agents for medical imaging. Keywords: medical imaging; contrast agents; α-cyclodextrin; β-cyclodextrin; γ-cyclodextrin; MRI; PET; CT; SPECT; PAI 1. Introduction Cyclodextrins (CDs) are chemically stable naturally occurring cyclic oligosaccharides consisting of multiple glucose subunits connected by α-1,4 glycosidic bonds [1,2]. There are three main types of CDs that contain six (α-CD), seven (β-CD), and eight (γ-CD) glucose subunits in a ring (Figure1). These cyclodextrin macromolecules are cone-shaped with a hydrophobic interior cavity and polar exterior surface [3]. Due to their non-toxic nature [1,4–6] and water solubility [7–9], CDs became widely used in various biomedical fields such as drug solubilization [7,10–12], drug delivery [8,13–17], and nucleic acid transfer [18–20]. Molecules 2020, 25, 5576; doi:10.3390/molecules25235576 www.mdpi.com/journal/molecules Molecules 2020, 25, 5576 2 of 27 Molecules 2020, 25, x FOR PEER REVIEW 2 of 27 Figure 1. ChemicalChemical structure structure of of ( (aa)) αα-cyclodextrin,-cyclodextrin, ( (b)) β-cyclodextrin,-cyclodextrin, and and ( (cc)) γγ-cyclodextrin.-cyclodextrin. ComparedCompared to to other other macrocyclic macrocyclic hosts, hosts, cyclodextrins cyclodextrins are areby far by the far most the most extensively extensively used in used host– in guesthost–guest chemistry chemistry applications applications and medical and medical imaging imaging [21–25]. [They21–25 tend]. They to be tend the tomacrocycle be the macrocycle of choice dueof choice to their due structural to their structural advantages advantages and robust and robustability abilityto form to forminclusion inclusion complexes complexes [21,26]. [21 ,An26]. inclusionAn inclusion complex complex is formed is formed when when a guest a guest molecule, molecule, commonly commonly a asmall small drug, drug, is is partially partially or or fully fully encapsulatedencapsulated inside inside the the host’s interior cavity [1,3]. [1,3]. In In the the case case of of cyclodextrins, cyclodextrins, their their preferred preferred guest guest moleculesmolecules tend tend to to be be hydrophobic, hydrophobic, making making them them suitable suitable for for binding binding in in the the hydrophobic hydrophobic interior. interior. Therefore, cyclodextrins possess possess the the ability ability to to form form inclusion inclusion complexes complexes with with a a wide variety of hydrophobichydrophobic guest molecules [26–28]. [26–28]. Formation Formation of of inclusion inclusion complexes, complexes, or or molecular molecular encapsulation, encapsulation, cancan affect affect the the physiochemical physiochemical properties properties of of the the drug drug or or molecule molecule itself, itself, such such as assolubility solubility and and rate rate of dissolutionof dissolution [3]. [ 3CDs]. CDs are are often often exploited exploited because because of of this this property property in in addition addition to to enhancing enhancing water water solubilitysolubility of of water-insoluble water-insoluble molecules [3]. [3]. The The exte exteriorrior of of cyclodextrin cyclodextrin is is predominantly predominantly hydrophilic hydrophilic duedue to the extensive hydrogenhydrogen bondingbonding network,network, making making it it a a biocompatible biocompatible agent agent for for a widea wide range range of ofapplications applications [1– 3[1–3,6–17].,6–17]. These These structural structural factors factors are largely are whylargely CDs why are favored CDs are when favored synthesizing when synthesizinginclusion complexes. inclusion Electronicscomplexes. and Electronics thermodynamics and thermodynamics both play a roleboth in play determining a role in determining if a CD will ifform a CD an will inclusion form an complex inclusion with complex a guest moleculewith a gues [1].t molecule The driving [1]. force The fordriving inclusion force complexationfor inclusion complexationinvolves various involves noncovalent various interactions noncovalent such interact as desolvation,ions such or as removal, desolvation, of water or moleculesremoval, of from water the moleculesinterior cavity from and the formation interior cavity of Van and der Waals,formatio hydrophobic,n of Van der and Waals, hydrogen hydrophobic, bonding interactions and hydrogen [29]. bondingThe major interactions driving forces [29]. for The cyclodextrin major driving complexation forces for arecyclodextrin van der Waals complexation interaction are and van hydrophobic der Waals interactioninteraction, and whereas hydrophobic hydrogen interaction, bonding and whereas electrostatic hydrogen interaction bonding mostly and electrostatic affect the conformation interaction mostlyof a particular affect the inclusion conformation complex of a [29 particular]. CD’s ability inclusion to form complex inclusion [29]. complexesCD’s ability with to form small inclusion organic complexesmolecules haswith pioneered small organic the field molecules of supramolecular has pioneered chemistry. the field More of supramolec recently, CDsular havechemistry. successfully More recently,been used CDs to buildhave successfully various molecular been used architectures to build various such asmolecular catenanes, architectures rotaxanes, such pseudorotaxanes, as catenanes, rotaxanes,polyrotaxanes, pseudorotaxanes, and other molecular polyrotaxanes, machines and [30 other,31]. molecular machines [30,31]. DuringDuring thethe pastpast few few decades, decades, cyclodextrins cyclodextrins have have become become of interest of interest as contrast as contrast agents and agents potential and potentialbiosensors biosensors for different for medicaldifferent imaging medical modalities imaging modalities [32]. In the [32]. context In the of context imaging, of CDs imaging, have beenCDs haveused been primarily used asprimarily a scaffold as to a supportscaffold andto support/or solubilize and/or smaller solubilize molecules smaller that molecules produce that or quenchproduce a orsignal quench for enhanceda signal for imaging. enhanced However, imaging. inHowever, a few cases, in a thefew uniquecases, the supramolecular unique supramolecular nature of thenature CD ofis essentialthe CD is inessential producing in producing the signal the for signal imaging. for imaging. Examples Examples of CD-containing of CD-containing constructs constructs that can that be canimaged be imaged by a wide by a variety wide variety of modern of modern imaging imaging technologies technologies are discussed are discussed herein. herein. MagneticMagnetic resonance resonance imaging imaging (MRI) (MRI) was was the the first first imaging modality to utilize cyclodextrins as contrastcontrast agents agents [33]. [33]. CD-based CD-based MRI MRI contrast contrast agents agents produced produced contrast contrast through through the reduction the reduction in spin- in lattice relaxation (T1) time of the water protons. There are two different established methods of spin-lattice relaxation (T1) time of the water protons. There are two different established methods synthesisof synthesis of CD-based of CD-based MRI MRI contrast contrast agents: agents: (1) host (1)–guest host–guest interactions interactions between between CD cavity CD and cavity metal– and organicmetal–organic complexes complexes [33,34] [33 and,34 ](2) and by (2) direct by direct conjugation conjugation of ofCDs CDs to tothe the metal–organic metal–organic complexes complexes through the external hydroxyl groups of CD molecule [35,36]. The reduction in T1 relaxation for CD- through the external hydroxyl groups of CD molecule [35,36]. The reduction in T1 relaxation for basedCD-based contrast contrast agents, agents, and therefore and therefore their contrast their contrast,,
Load more

Recommended publications
  • 232383538.Pdf
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by University of Groningen University of Groningen X-ray Structure of Cyclodextrin Glycosyltransferase Complexed with Acarbose. Implications for the Catalytic Mechanism of Glycosidases STROKOPYTOV, B; PENNINGA, D; ROZEBOOM, HJ; KALK, KH; DIJKHUIZEN, L; DIJKSTRA, BW Published in: Biochemistry DOI: 10.1021/bi00007a018 IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below. Document Version Publisher's PDF, also known as Version of record Publication date: 1995 Link to publication in University of Groningen/UMCG research database Citation for published version (APA): STROKOPYTOV, B., PENNINGA, D., ROZEBOOM, HJ., KALK, KH., DIJKHUIZEN, L., & DIJKSTRA, BW. (1995). X-ray Structure of Cyclodextrin Glycosyltransferase Complexed with Acarbose. Implications for the Catalytic Mechanism of Glycosidases. Biochemistry, 34(7), 2234-2240. https://doi.org/10.1021/bi00007a018 Copyright Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons). Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the number of authors shown on this cover page is limited to 10 maximum.
    [Show full text]
  • Cyclodextrin Enhanced the Soluble Expression of Bacillus Clarkii Γ-Cgtase in Escherichia Coli Lei Wang1,2, Sheng Chen1,2 and Jing Wu1,2*
    Wang et al. BMC Biotechnology (2018) 18:72 https://doi.org/10.1186/s12896-018-0480-8 RESEARCHARTICLE Open Access Cyclodextrin enhanced the soluble expression of Bacillus clarkii γ-CGTase in Escherichia coli Lei Wang1,2, Sheng Chen1,2 and Jing Wu1,2* Abstract Background: Cyclodextrin glycosyltransferases (CGTases) catalyze the synthesis of cyclodextrins, which are circular α-(1,4)-linked glucans used in many applications in the industries related to food, pharmaceuticals, cosmetics, chemicals, and agriculture, among others. Economic use of these CGTases, particularly γ-CGTase, requires their efficient production. In this study, the effects of chemical chaperones, temperature and inducers on cell growth and the production of soluble γ-CGTase by Escherichia coli were investigated. Results: The yield of soluble γ-CGTase in shake-flask culture approximately doubled when β-cyclodextrin was added to the culture medium as a chemical chaperone. When a modified two-stage feeding strategy incorporating 7.5 mM β-cyclodextrin was used in a 3-L fermenter, a dry cell weight of 70.3 g·L− 1 was achieved. Using this cultivation approach, the total yield of γ-CGTase activity (50.29 U·mL− 1) was 1.71-fold greater than that observed in the absence of β-cyclodextrin (29.33 U·mL− 1). Conclusions: Since β-cyclodextrin is inexpensive and nontoxic to microbes, these results suggest its universal application during recombinant protein production. The higher expression of soluble γ-CGTase in a semi-synthetic medium showed the potential of the proposed process for the economical production of many enzymes on an industrial scale. Keywords: Cyclodextrin glycosyltransferase, Cyclodextrin, Chemical chaperones, Overexpression, Escherichia coli Background biodegradation [3]; thus, γ-cyclodextrin has found much Cyclodextrin glycosyltransferases (EC 2.4.1.19, CGTase) wider application in industrial settings.
    [Show full text]
  • Effects of Progesterone and Testosterone on Cocaine Self-Administration and Cocaine Discrimination by Female Rhesus Monkeys
    Neuropsychopharmacology (2011) 36, 2187–2199 & 2011 American College of Neuropsychopharmacology. All rights reserved 0893-133X/11 www.neuropsychopharmacology.org Effects of Progesterone and Testosterone on Cocaine Self-Administration and Cocaine Discrimination by Female Rhesus Monkeys Nancy K Mello*,1, Inge M Knudson1, Maureen Kelly1, Peter A Fivel1 and Jack H Mendelson1 1 Alcohol and Drug Abuse Research Center, McLean HospitalFHarvard Medical School, Belmont, MA, USA The neuroactive steroid hormone progesterone attenuates cocaine’s abuse-related effects in women and in rodents under some conditions, but the effects of testosterone are unknown. We compared the acute effects of progesterone (0.1, 0.2, and 0.3 mg/kg, intramuscularly (i.m.)), testosterone (0.001, 0.003, and 0.01 mg/kg, i.m.), and placebo on cocaine self-administration and cocaine discrimination dose–effect curves in female rhesus monkeys. Cocaine self-administration (0.03 mg/kg per inj.) was maintained on a fixed ratio 30 schedule of reinforcement, and monkeys had unlimited access to cocaine for 2 h each day. Cocaine doses were administered in an irregular order during each dose–effect curve determination, and the same dose order was used in each subject in all treatment conditions. Blood samples for hormone analysis were collected at the end of each test session. Banana-flavored food pellets (1 g) were also available in three 1-h daily sessions. In drug discrimination studies, the effects of pretreatment with progesterone (0.032–0.32 mg/kg, i.m.) and testosterone (0.001–0.01 mg/kg, i.m.) on the discriminative stimulus effects of cocaine (0.18 mg/kg, i.m.) were examined.
    [Show full text]
  • Cyclodextrin-Enabled Insulin Delivery
    VOLUME 32. No 2. VOLUME 32. No. 3. MARCH 2018 ISSN 0951-256X Cyclodextrin-enabled Insulin Delivery Introduction Insulin is a peptide hormone produced by beta cells in pancreatic islets. Its main task is the regulation of the metabolism of carbohydrates, fats and protein. In diabetes the insulin production is not enough to keep the blood sugar levels within normal bounds, therefore external insulin should be supplied. The human insulin is composed of 51 amino acids and 3 disulfide bonds; it has a molecular mass of 5808 Da and low aqueous solubility. Bovine insulin differs from human in only 3 amino acids and porcine insulin in one. Insulin is produced and stored in the body as a hexamer (Fig. 1), while the active form is the monomer. The hexamer is much more stable than the monomer. Fig. 1 The structure of insulin hexamer (the magenta sphere is zinc ion, wikipedia) Human insulin is manufactured by recombinant DNA technology, but some patients observing adverse effects to synthetic insulin use animal-source insulin. The oral administration of peptides and proteins is of low efficiency because of the enzymatic degradation in the gastrointestinal tract and poor transport characteristics. That is the reason why insulin is administered via parenteral injections. Edited and produced by: CYCLOLAB – page 1 VOLUME 32. No 2. While developing the devices used for insulin injections (to reduce the pain and local irritation as well as the frequency of application), researchers have been taking continuous efforts on finding novel non-invasive formulations. • One of the aims is protection of insulin from proteolysis in the digestive tract so that it can be administered orally or sublingually.
    [Show full text]
  • Cyclodextrin-Catalyzed Organic Synthesis: Reactions, Mechanisms, and Applications
    molecules Review Cyclodextrin-Catalyzed Organic Synthesis: Reactions, Mechanisms, and Applications Chang Cai Bai 1,† ID , Bing Ren Tian 1,†, Tian Zhao 1, Qing Huang 1,2,* and Zhi Zhong Wang 1,2,* 1 School of Pharmacy, Ningxia Medical University, Yinchuan 750004, China; [email protected] (C.C.B.); [email protected] (B.R.T.); [email protected] (T.Z.) 2 Key Laboratory of Hui Ethnic Medicine Modernization, Ministry of Education, Yinchuan 750004, China * Correspondence: [email protected] (Q.H.); [email protected] (Z.Z.W.); Tel.: +86-0951-688-0582 (Z.Z.W.) † These authors contributed equally to this work. Received: 2 August 2017; Accepted: 2 September 2017; Published: 7 September 2017 Abstract: Cyclodextrins are well-known macrocyclic oligosaccharides that consist of α-(1,4) linked glucose units and have been widely used as artificial enzymes, chiral separators, chemical sensors, and drug excipients, owing to their hydrophobic and chiral interiors. Due to their remarkable inclusion capabilities with small organic molecules, more recent interests focus on organic reactions catalyzed by cyclodextrins. This contribution outlines the current progress in cyclodextrin-catalyzed organic reactions. Particular emphases are given to the organic reaction mechanisms and their applications. In the end, the future directions of research in this field are proposed. Keywords: cyclodextrin; catalysis; mechanism; green chemistry; organic reaction; asymmetric reaction 1. Introduction Supramolecular chemistry is defined as the chemistry of the intermolecular bond, and focuses on the chemical systems made up of a discrete number of assembled molecular subunits or components. It aims at developing highly complex chemical systems from molecular components reversibly held together by non-covalent intermolecular forces [1,2].
    [Show full text]
  • RR-17: Scoping Review of Prenatal
    NTP RESEARCH REPOrt ON THE SCOPING REVIEW OF PRENATAL EXPOSURE TO PROGESTOGENS AND ADVERSE HEALTH OUTCOMES NTP RR 17 SEPTEMBER 2020 NTP Research Report on the Scoping Review of Prenatal Exposure to Progestogens and Adverse Health Outcomes Research Report 17 September 2020 National Toxicology Program Public Health Service U.S. Department of Health and Human Services ISSN: 2473-4756 Research Triangle Park, North Carolina, USA Scoping Review of Prenatal Exposure to Progestogens and Adverse Health Outcomes Foreword The National Toxicology Program (NTP), established in 1978, is an interagency program within the Public Health Service of the U.S. Department of Health and Human Services. Its activities are executed through a partnership of the National Institute for Occupational Safety and Health (part of the Centers for Disease Control and Prevention), the Food and Drug Administration (primarily at the National Center for Toxicological Research), and the National Institute of Environmental Health Sciences (part of the National Institutes of Health), where the program is administratively located. NTP offers a unique venue for the testing, research, and analysis of agents of concern to identify toxic and biological effects, provide information that strengthens the science base, and inform decisions by health regulatory and research agencies to safeguard public health. NTP also works to develop and apply new and improved methods and approaches that advance toxicology and better assess health effects from environmental exposures. NTP reports the findings from many of its studies in the NTP Technical Report and Monograph series. NTP uses the Research Report series, which began in 2016, to report on work that does not fit readily into one of those two series, such as pilot studies, assay development or optimization studies, literature surveys or scoping reviews, and handbooks on NTP procedures or study specifications.
    [Show full text]
  • Download (Accessed on 6 November 2020)
    biomolecules Review Cyclodextrins, Natural Compounds, and Plant Bioactives—A Nutritional Perspective Svenja Wüpper *, Kai Lüersen and Gerald Rimbach Institute of Human Nutrition and Food Science, University of Kiel, Hermann-Rodewald-Strasse 6, 24118 Kiel, Germany; [email protected] (K.L.); [email protected] (G.R.) * Correspondence: [email protected]; Tel.: +49-431-880-5334 Abstract: Cyclodextrins (CDs) are a group of cyclic oligosaccharides produced from starch or starch derivatives. They contain six (αCD), seven (βCD), eight (γCD), or more glucopyranose monomers linked via α-1,4-glycosidic bonds. CDs have a truncated cone shape with a hydrophilic outer wall and a less hydrophilic inner wall, the latter forming a more apolar internal cavity. Because of this special architecture, CDs are soluble in water and can simultaneously host lipophilic guest molecules. The major advantage of inclusion into CDs is increased aqueous solubility of such lipophilic substances. Accordingly, we present studies where the complexation of natural compounds such as propolis and dietary plant bioactives (e.g., tocotrienol, pentacyclic triterpenoids, curcumin) with γCD resulted in improved stability, bioavailability, and bioactivity in various laboratory model organisms and in humans. We also address safety aspects that may arise from increased bioavailability of plant extracts or natural compounds owing to CD complexation. When orally administered, α- and βCD—which are inert to intestinal digestion—are fermented by the human intestinal flora, while γCD is almost completely degraded to glucose units by α-amylase. Hence, recent reports indicate that empty γ CD supplementation exhibits metabolic activity on its own, which may provide opportunities for new applications.
    [Show full text]
  • Article J Incl Phenom Macrocycl Chem 2007
    J Incl Phenom Macrocycl Chem (2007) 57:283–288 DOI 10.1007/s10847-006-9174-2 ORIGINAL ARTICLE Water soluble progesterone–hydroxypropyl-b-cyclodextrin complex for injectable formulations G. Zoppetti Æ N. Puppini Æ M. Pizzutti Æ A. Fini Æ T. Giovani Æ S. Comini Received: 15 May 2006 / Accepted: 20 October 2006 / Published online: 28 February 2007 Ó Springer Science+Business Media B.V. 2007 Abstract The use of cyclodextrin to increase the have developed a production process in which the water solubility of progesterone (P) was described by residual unreacted b-cyclodextrin is separated from Pitha as a complex with b-cyclodextrin and derivates the HPBCD by the formation of the insoluble inclu- to obtain a water soluble formulation (Pitha, J.: US sion complex (Zoppetti et al.: European Patent de- patent n. 4,727,064). Hydroxypropyl-b-cyclodextrin posit n. 05108494.5). The resulting P/HPBCD contains (HPBCD) has a high water solubility which allows the up to 0.1% of residual b-cyclodextrin and does not solubilization of high quantity of P. Considering a 1:2 produce precipitate during the stability study. The guess/host complex stoichiometry it is possible to complex stoichiometry and the complex constant were obtain up to 50 mg/ml of P concentration, which is a calculated by the phase solubility study according to considerable dosage for drug development in the Higuchi and Connors (Adv. Anal. Chem. Instrum. 4, progesterone therapy. In our drug development the P/ 117, 1965) and the presence of the inclusion complex HPBCD complex in water showed the formation of a was demonstrated by DSC, NMR, X-ray, FTIR.
    [Show full text]
  • (Jordanella Floridae) Over One Complete Life-Cycle
    The Effects of Hydroxypropyl-β-Cyclodextrin on the American Flagfish (Jordanella floridae) Over One Complete Life-Cycle by Jordan Christopher Anderson A Thesis Submitted in Partial Fulfillment of the Requirements of the Degree of Masters of Science in The Faculty of Science Applied Bioscience University of Ontario Institute of Technology August, 2013 © Jordan Christopher Anderson, 2013 Abstract Understanding the impacts of pharmaceuticals and personal care products (PPCPs) on aquatic ecosystems is an important issue in aquatic toxicology. Many PPCPs have been shown to cause effects on aquatic biota within detected environmental ranges. One compound of particular interest is hydroxylpropyl-β-cyclodextrin (HPβCD), the active ingredient in Febreeze®, and widely used for many applications. HPβCD is amphiphilic, toroidal in shape, and able to form non-covalent inclusion complexes with a variety of guest molecules. HPβCD has been shown to reduce volatility as well as improve the aqueous solubility of apolar guest compounds. As such, the use of HPβCD in the pharmaceutical and personal care industry has dramatically increased. With increasing potential for entering the environment through wastewater treatment plant (WWTP) effluent, HPβCD poses an unknown risk to non-target aquatic biota. As a result, a 145-day chronic full life-cycle exposure using American flagfish (Jordanella floridae) was completed using flow-through concentrations of 0 (control), 5, 16, 50,160, 500, and 1600 µg/L of HPβCD maintained via a peristaltic pump. No significant differences were observed in growth, condition factor (K) and hepatosomatic index (HSI) when chronically exposed to HPβCD (P ≤ 0.05). A significant increase in female gonadosomatic index (GSI) occurred in those exposed to HPβCD (P ≤ 0.05).
    [Show full text]
  • Supramolecular Hydrogels of Β-Cyclodextrin Linked to Calcium Homopoly-L- Guluronate for Release of Coumarins with Trypanocidal Activity T ⁎ M
    Carbohydrate Polymers 204 (2019) 170–181 Contents lists available at ScienceDirect Carbohydrate Polymers journal homepage: www.elsevier.com/locate/carbpol Supramolecular hydrogels of β-cyclodextrin linked to calcium homopoly-L- guluronate for release of coumarins with trypanocidal activity T ⁎ M. Moncada-Basualtoa,b, , B. Matsuhiroa, A. Mansillac,d, M. Lapiere, J.D. Mayae, C. Olea-Azarb a Departamento de Ciencias del Ambiente, Facultad de Química y Biología, Universidad de Santiago de Chile, Av. L. B. O’Higgins 3363, Santiago, Chile b Departamento de Química Inorgánica y Analítica, Facultad de Ciencias Química y Farmacéuticas, Universidad de Chile, Av. Sergio Livingstone 1007, Santiago, Chile c Laboratorio de Macroalgas Antárticas y Subantárticas, Universidad de Magallanes, Av. Bulnes 1465, Punta Arenas, Chile d Instituto de Ecología y Biodiversidad, Chile e Departamento de Farmacología Molecular y Clínica, Facultad de Medicina, Universidad de Chile, Av. Independencia 1107, Santiago, Chile ARTICLE INFO ABSTRACT Keywords: Association constants and thermodynamicsparameters on inclusion of four 3-amido coumarins that present Homopoly-L-guluronate trypanocidal activity, into 6-amino-β-cyclodextrin (1:1 stoichimetry) were determined. In addition, pure 3-Amidocoumarins homopolymeric-α-L-guluronate fraction prepared by partial hydrolysis of sodium alginate from Sub-Antarctic Inclusion complex Kelp Durvillaea antarctica was conjugated with 6-amino-β-cyclodextrin (64% yield). To glycoconjugates, 3-amido Trypanosoma cruzi coumarins were incorporated (73% of encapsulation) and supramolecular hydrogels were prepared by gelation Supramolecular hydrogel with Ca2+ ions. Sub-Antarctic macroalgae The trypanocidal activity of the inclusion complexes increased by 10%. Likewise, an increase in diffusion in artificial membrane was observed (13%). It was found that the inclusion complexes increased the variation of the mitochondrial potential of T.
    [Show full text]
  • Alpha-Cyclodextrin Attenuates the Glycemic and Insulinemic Impact of White Bread in Healthy Male Volunteers
    foods Article Alpha-Cyclodextrin Attenuates the Glycemic and Insulinemic Impact of White Bread in Healthy Male Volunteers Albert Bär 1,* , Ioannis Diamantis 2 and Werner P. Venetz 3 1 Bioresco Ltd., 4054 Basel, Switzerland 2 Gastro Center, 2502 Biel, Switzerland; [email protected] 3 Datagen AG, 3930 Visp, Switzerland; [email protected] * Correspondence: [email protected] Received: 28 November 2019; Accepted: 3 January 2020; Published: 7 January 2020 Abstract: The demonstration of a physiological benefit has recently become an indispensible element of the definition of dietary fibers. In the here-reported pilot study, the effect of alpha-cyclodextrin (alpha-CD) on the postprandial glycemic and insulinemic effect of starch was examined. Twelve fasted, healthy male volunteers received, on three subsequent days, a test breakfast consisting of (A) 100 g fresh white bread (providing 50 g starch) and 250 mL drinking water, (B) the same bread with a supplement of 10 g alpha-CD dissolved in the drinking water, and (C) 25 g alpha-CD dissolved in drinking water. Capillary and venous blood was sampled before the breakfast and in regular intervals for a three-hour period thereafter. Glucose was determined in capillary blood and insulin in the plasma of venous blood samples. Breakfast (A) led to a rapid rise in blood glucose and insulin. In breakfast (B), alpha-CD reduced the areas under the curve of blood glucose and insulin significantly by 59% and 57%, respectively, demonstrating that alpha-CD inhibits and thereby delays starch digestion. Treatment (C) was not associated with a rise of blood glucose. Hence, alpha-CD complies with the current definition of dietary fiber in every respect.
    [Show full text]
  • Background Review for Cyclodextrins Used As Excipients
    20 November 2014 EMA/CHMP/333892/2013 Committee for Human Medicinal Products (CHMP) Background review for cyclodextrins used as excipients In the context of the revision of the guideline on ‘Excipients in the label and package leaflet of medicinal products for human use’ (CPMP/463/00 Rev. 1) Draft report published in support to the propylene glycol Q&A document. For information only 30 Churchill Place ● Canary Wharf ● London E14 5EU ● United Kingdom Telephone +44 (0)20 3660 6000 Facsimile +44 (0)20 3660 5555 Send a question via our website www.ema.europa.eu/contact An agency of the European Union © European Medicines Agency, 2014. Reproduction is authorised provided the source is acknowledged. Table of contents Executive summary ..................................................................................... 3 Introduction ................................................................................................ 3 1. Characteristics......................................................................................... 3 2. Kinetic/toxicological data and clinical safety .......................................... 4 2.1. Oral products ....................................................................................................... 4 2.2. Nasal and pulmonary products ............................................................................... 5 2.3. Rectal products .................................................................................................... 6 2.4. Dermal products .................................................................................................
    [Show full text]