Special Issue "New Frontiers in Cyclodextrin Technologies"

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Biopharmaceuticals".

Deadline for manuscript submissions: 4 November 2021.

Special Issue Editors

Prof. Dr. Laura Catenacci
E-Mail Website
Guest Editor
Department of Drug Sciences, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy
Interests: solid-state characterization; thermal analysis; cyclodextrins; drug delivery; poorly soluble drugs formulation
Special Issues and Collections in MDPI journals
Dr. Milena Sorrenti
E-Mail Website
Guest Editor
Università degli Studi di Pavia, Department of Drug Sciences, Pavia, Italy
Interests: solid-state characterization; cyclodextrins; drug delivery; poorly soluble drugs formulation
Special Issues and Collections in MDPI journals
Prof. Dr. Maria Cristina Bonferoni
E-Mail Website
Guest Editor
Department of Drug Sciences, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy
Interests: drug delivery; nanomedicine; poorly soluble drugs formulation
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

Thanks to their excellent biocompatibility, ability to form inclusion complexes, functionalizability, cyclodextrins and their derivatives are especially attractive for new applications. Cyclodextrins are natural macrocyclic oligomers composed of a-D-glucopyranose units linked by a-D-1,4 glycosidic bonds to form torus-shaped molecules characterized by a hydrophobic central cavity and a hydrophilic surface. This conformation is responsible for non-covalent inclusion complex formation with organic molecules, which are generally included within the hydrophobic cyclodextrin cavity. This ability can be used to improve drug solubility, dissolution, and/or permeability, thus enhancing their bioavailability. Other applications include improving chemical and physical stability, preventing gastrointestinal irritation, reducing or eliminating unpleasant odors and flavors, preventing drug–drug or drug–excipient interactions, and converting oils and liquid drugs into microcrystalline or amorphous powders.

Moreover, the cyclodextrins can be modified to change their physicochemical properties and can be combined with other molecules to form cyclodextrin/polymer networks or to create supramolecular structures in the form of nanoparticles, micelles, vesicles, nanogels, nanopolyplexes, hydrogels, and highly complex superstructures and multifunctional systems.

The versatility of cyclodextrins and their derivatives make them suitable for many applications in pharmaceutical, analytical chemistry, agriculture, food, and cosmetic fields.

The aim of this Special Issue is to summarize the state of the art of cyclodextrins’ application, and to elucidate the new frontiers in cyclodextrin-based supramolecular systems.

Prof. Laura Catenacci
Dr. Milena Sorrenti
Prof. Dr. Maria Cristina Bonferoni
Guest Editors

Manuscript Submission Information

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Keywords

  • Cyclodextrins
  • Inclusion complexes
  • Drug delivery systems
  • Supramolecular systems

Published Papers (6 papers)

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Research

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Article
Guest-Mediated Reversal of the Tumbling Process in Phosphorus-Dendritic Compounds Containing β-Cyclodextrin Units: An NMR Study
Pharmaceuticals 2021, 14(6), 556; https://0-doi-org.brum.beds.ac.uk/10.3390/ph14060556 - 11 Jun 2021
Viewed by 1239
Abstract
The conformational study of dendritic platforms containing multiple β-cyclodextrin (βCD) units in the periphery is relevant to determine the availability of βCD cavities for the formation of inclusion complexes in aqueous biological systems. In this work, we performed a detailed conformational analysis in [...] Read more.
The conformational study of dendritic platforms containing multiple β-cyclodextrin (βCD) units in the periphery is relevant to determine the availability of βCD cavities for the formation of inclusion complexes in aqueous biological systems. In this work, we performed a detailed conformational analysis in D2O, via 1D and 2D NMR spectroscopy of a novel class of phosphorus dendritic compounds of the type P3N3-[O-C6H4-O-(CH2)n-βCD]6 (where n = 3 or 4). We unambiguously demonstrated that a functionalized glucopyranose unit of at least one βCD unit undergoes a 360° tumbling process, resulting in a deep inclusion of the spacer that binds the cyclodextrin to the phosphorus core inside the cavity, consequently limiting the availability of the inner cavities. In addition, we confirmed through NMR titrations that this tumbling phenomenon can be reversed for all βCD host units using a high-affinity guest, namely 1-adamantanecarboxylic acid (AdCOOH). Our findings have demonstrated that it is possible to create a wide variety of multi-functional dendritic platforms. Full article
(This article belongs to the Special Issue New Frontiers in Cyclodextrin Technologies)
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Article
Improving the Solubilization and Bioavailability of Arbidol Hydrochloride by the Preparation of Binary and Ternary β-Cyclodextrin Complexes with Poloxamer 188
Pharmaceuticals 2021, 14(5), 411; https://0-doi-org.brum.beds.ac.uk/10.3390/ph14050411 - 26 Apr 2021
Cited by 1 | Viewed by 645
Abstract
In the current study, the effect of poloxamer 188 on the complexation efficiency and dissolution of arbidol hydrochloride (ADL), a broad-spectrum antiviral agent, with β-cyclodextrin (β-CD) was investigated. Phase solubility studies confirmed a stoichiometry of a 1:1 ratio for both ADL:β-CD and ADL/β-CD [...] Read more.
In the current study, the effect of poloxamer 188 on the complexation efficiency and dissolution of arbidol hydrochloride (ADL), a broad-spectrum antiviral agent, with β-cyclodextrin (β-CD) was investigated. Phase solubility studies confirmed a stoichiometry of a 1:1 ratio for both ADL:β-CD and ADL/β-CD with a 1% poloxamer 188 system with an AL type of phase solubility curve. The stability constants (K1:1) calculated from the AL type diagram were 550 M-1 and 2134 M-1 for AD:β-CD and ADL/β-CD with 1% poloxamer 188, respectively. The binary ADL/β-CD and ternary ADL/β-CD with 1% poloxamer 188 complexes were prepared by kneading and a solvent evaporation method and were characterized by aqueous solubility, FTIR, PXRD, DSC and SEM in vitro studies. The solubility (13.1 fold) and release of ADL were markedly improved in kneaded ternary ADL/β-CD with 1% poloxamer 188 (KDB). The binding affinity of ADL and β-CD was confirmed by 1H NMR and 2D ROSEY studies. The ternary complex (KDB) was further subjected for in vivo pharmacokinetic studies in rats and a significant improvement in the bioavailability (2.17 fold) was observed in comparison with pure ADL. Therefore, it can be concluded that the solubilization and bioavailability of ADL can be remarkably increased by ADL/β-CD complexation in the presence of a third component, poloxamer 188. Full article
(This article belongs to the Special Issue New Frontiers in Cyclodextrin Technologies)
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Article
Implementation of an Enzyme Membrane Reactor to Intensify the α-O-Glycosylation of Resveratrol Using Cyclodextrins
Pharmaceuticals 2021, 14(4), 319; https://0-doi-org.brum.beds.ac.uk/10.3390/ph14040319 - 01 Apr 2021
Cited by 1 | Viewed by 609
Abstract
The O-glycosylation of resveratrol increases both its solubility in water and its bioavailability while preventing its oxidation, allowing a more efficient use of this molecule as a bioactive ingredient in pharmaceutical and cosmetic applications. Resveratrol O-glycosides can be obtained by enzymatic [...] Read more.
The O-glycosylation of resveratrol increases both its solubility in water and its bioavailability while preventing its oxidation, allowing a more efficient use of this molecule as a bioactive ingredient in pharmaceutical and cosmetic applications. Resveratrol O-glycosides can be obtained by enzymatic reactions. Recent developments have made it possible to selectively obtain resveratrol α-glycosides from the β-cyclodextrin–resveratrol complex in water with a yield of 35%. However, this yield is limited by the partial hydrolysis of the resveratrol glycosides produced during the reaction. In this study, we propose to intensify this enzymatic reaction by coupling the enzymatic reactor to a membrane process. Firstly, membrane screening was carried out at the laboratory scale and led to the choice of a GE polymeric membrane with a cut-off of 1 kDa. This membrane allowed the retention of 65% of the β-cyclodextrin–resveratrol complex in the reaction medium and the transfer of 70% of the resveratrol α-O-glycosides in the permeate. In a second step, this membrane was used in an enzymatic membrane reactor and improved the yield of the enzymatic glycosylation up to 50%. Full article
(This article belongs to the Special Issue New Frontiers in Cyclodextrin Technologies)
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Article
Covalently Functionalized Carbon Nano-Onions Integrated Gelatin Methacryloyl Nanocomposite Hydrogel Containing γ-Cyclodextrin as Drug Carrier for High-Performance pH-Triggered Drug Release
Pharmaceuticals 2021, 14(4), 291; https://0-doi-org.brum.beds.ac.uk/10.3390/ph14040291 - 25 Mar 2021
Cited by 4 | Viewed by 1054
Abstract
Herein, poly (n-(4-aminophenyl) methacrylamide)) carbon nano-onions (PAPMA-CNOs = f-CNOs) and γ-cyclodextrin/DOX-complex (CD) reinforced gelatin methacryloyl (GelMA)/f-CNOs/CD supramolecular hydrogel interfaces were fabricated using the photo-crosslinking technique. The physicochemical properties, morphology, biodegradation, and swelling properties of hydrogels were investigated. The composite hydrogels demonstrated [...] Read more.
Herein, poly (n-(4-aminophenyl) methacrylamide)) carbon nano-onions (PAPMA-CNOs = f-CNOs) and γ-cyclodextrin/DOX-complex (CD) reinforced gelatin methacryloyl (GelMA)/f-CNOs/CD supramolecular hydrogel interfaces were fabricated using the photo-crosslinking technique. The physicochemical properties, morphology, biodegradation, and swelling properties of hydrogels were investigated. The composite hydrogels demonstrated enriched drug release under the acidic conditions (pH 4.5 = 99%, and pH 6.0 = 82%) over 18 days. Owing to the f-CNOs inclusion, GelMA/f-CNOs/CD supramolecular hydrogels presented augmented tensile strength (σult = 356.1 ± 3.4 MPa), toughness (K = 51.5 ± 0.24 Jg−1), and Young’s modulus (E = 41.8 ± 1.4 GPa). The strengthening of GelMA/f-CNOs/CD hydrogel systems indicates its good dispersion and the degree of polymer enveloping of f-CNOs within GelMA matrixes. Furthermore, the obtained hydrogels showed improved cell viability with human fibroblast cells. Nevertheless, the primed supramolecular hydrogels would pave the way for the controlled delivery systems for future drug delivery. Full article
(This article belongs to the Special Issue New Frontiers in Cyclodextrin Technologies)
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Article
Effect of Methyl–β–Cyclodextrin and Trehalose on the Freeze–Drying and Spray–Drying of Sericin for Cosmetic Purposes
Pharmaceuticals 2021, 14(3), 262; https://0-doi-org.brum.beds.ac.uk/10.3390/ph14030262 - 15 Mar 2021
Cited by 3 | Viewed by 772
Abstract
Sericin is a protein extracted from Bombyx mori silk cocoons. Over the last decade, this wastewater product of the textile industry has shown many interesting biological properties. This protein is widely used in the cosmetic and biomedical fields. In this study, sericin has [...] Read more.
Sericin is a protein extracted from Bombyx mori silk cocoons. Over the last decade, this wastewater product of the textile industry has shown many interesting biological properties. This protein is widely used in the cosmetic and biomedical fields. In this study, sericin has been obtained via a High–Temperature High–Pressure degumming process, and was dried using the freeze–drying (fd) and spray–drying (sd) techniques. Proteins tend to collapse during drying, hence, sericin has been dried in the presence of two selected carrier agents: methyl–β–cyclodextrin and trehalose. The obtained powders have been analyzed using thermal investigation, microscopy (optical, SEM), and granulometric and spectroscopic analyses. Moreover, the percentage yield of the spray–drying process has been calculated. Both the agents were able to significantly improve the drying process, without altering the physico–chemical properties of the protein. In particular, the co–spray–drying of sericin with methyl–β–cyclodextrin and trehalose gave good process yields and furnished a powder with low moisture content and handling properties that are better than those of the other studied dried products. These characteristics seem to be appropriate and fruitful for the manufacturing of cosmetic raw materials. Full article
(This article belongs to the Special Issue New Frontiers in Cyclodextrin Technologies)
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Review

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Review
Supercritical Carbon Dioxide as a Green Alternative to Achieve Drug Complexation with Cyclodextrins
Pharmaceuticals 2021, 14(6), 562; https://0-doi-org.brum.beds.ac.uk/10.3390/ph14060562 - 11 Jun 2021
Viewed by 777
Abstract
Cyclodextrins are widely used in pharmaceutics to enhance the bioavailability of many drugs. Conventional drug/cyclodextrin complexation techniques suffer from many drawbacks, such as a high residual content of toxic solvents in the formulations, the degradation of heat labile drugs and the difficulty in [...] Read more.
Cyclodextrins are widely used in pharmaceutics to enhance the bioavailability of many drugs. Conventional drug/cyclodextrin complexation techniques suffer from many drawbacks, such as a high residual content of toxic solvents in the formulations, the degradation of heat labile drugs and the difficulty in controlling the size and morphology of the product particles. These can be overcome by supercritical fluid technology thanks to the outstanding properties of supercritical CO2 (scCO2) such as its mild critical point, its tunable solvent power, and the absence of solvent residue after depressurization. In this work the use of scCO2 as an unconventional medium to achieve the complexation with native and substituted cyclodextrins of over 50 drugs, which belong to different classes, are reviewed. This can be achieved with different approaches such as the “supercritical solvent impregnation” and “particle-formation” techniques. The different techniques are discussed to point out how they affect the complexation mechanism and efficiency, the physical state of the drug as well as the particle size distribution and morphology, which finally condition the release kinetics and drug bioavailability. When applicable, the results obtained for the same drug with various cyclodextrins, or different complexation techniques are compared with those obtained with conventional approaches. Full article
(This article belongs to the Special Issue New Frontiers in Cyclodextrin Technologies)
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Title: γ-Cyclodextrin Integrated Gelatin Methacryloyl Hydrogel Interfacial Engineering Enable pH-Triggered Drug Release with Augmented Mechanical Properties  
Author: Narmidi Mamidi
Affiliation: School of Engineering and Science, Tecnológico de Monterrey, Eugenio Garza Sada 2501, Col. Tecnológico, CP 64849, Monterrey, Nuevo Leon, Mexico
Abstract: Supramolecular hydrogel interfaces confer control over the physicochemical and structural properties in a dynamic, reversible, and biomimetic manner. The design of supramolecular hydrogels with augmented physicochemical characteristics, functional, and structural recapitulation of damaged organs is vital for clinical applications. Herein, PAPMA-CNOs (f-CNOs) and γ-cyclodextrin (CD) reinforced gelatin methacryloyl (GelMA)/f-CNOs/CD supramolecular hydrogel interfaces were formulated for stimuli-responsive drug release. The physicochemical properties, morphology, biodegradation, and swelling properties of hydrogels were investigated. In vitro drug release measurements of hydrogels exhibited excellent drug release under the acidic conditions (pH 4.5 = 99%, and pH 6.0 = 95%) and moderate drug release in physiological conditions (pH 7.4 = 70%) over 18 days. Owing to the f-CNOs inclusion, GelMA/f-CNOs/CD supramolecular hydrogels presented excellent tensile strength (σ­­ult = 356.1 ± 3.4 MPa), toughness (K = 51.5 ± 0.24 Jg-1), and Young’s modulus (E = 41.8 ± 1.4 GPa). Furthermore, the obtained hydrogels showed improved cell viability with human fibroblast cells. Nevertheless, the primed supramolecular hydrogels would pave the way for the controlled drug delivery systems for future biomedical applications.
Keywords: GelMA/f-CNOs/CD supramolecular hydrogels, stimuli-responsive drug release, mechanical properties, cell viability

Title: Supercritical carbon dioxide as a green alternative to achieve drug complexation with cyclodextrins
Author: Mauro Banchero*
Affiliation: Dipartimento Scienza Applicata e Tecnologia, Politecnico di Torino, Corso Duca degli Abruzzi, 24, Torino, Italy; [email protected]
Abstract: Cyclodextrins are widely used in pharmaceutics to enhance the bioavailabiliy of many drugs. Conventional drug/cyclodextrin complexation techniques suffer from many drawbacks, such as a high residual content of toxic solvents in the final product, the degradation of heat labile drugs and the difficulty in controlling the size and morphology of the product particles. These can be overcome by supercritical fluid technology thanks to the outstanding properties of supercritical CO2 (scCO2) such as its mild critical point, its tunabe solvent power and the absence of solvent residue after depressurization.
In this work the most recent advances in the use of scCO2 as an unconventional medium to achieve the complexation of many kinds of drugs with native and substituted cyclodextrins are reviewed. The different techniques are discussed to point out how they affect the complexation efficiency, the physical state of the drug as well as the particle size distribution and morphology, which finally condition the release kinetics and drug biovailability.

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