Comparative Studies of Mechanochemically Synthesized Insoluble Beta-Cyclodextrin Polymers

Jicsinszky, László; Bucciol, Fabio; Manzoli, Maela; Cravotto, Giancarlo

doi:10.2174/1385272825666210730105716

Cited by 5 publications

(10 citation statements)

References 88 publications

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“…Menuel et al reported the first natural cyclodextrin derivatizations on the secondary hydroxyl rim [ 18 ]. A further extension followed the pioneering works, using high-energy ball milling to synthesize randomly substituted CDs [ 19 , 26 ] and insoluble CD polymers [ 20 , 27 ]. Comparing the reaction products with those of classical solution methods also showed the limitations.…”

Section: Discussionmentioning

confidence: 99%

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Comparison of the Conventional and Mechanochemical Syntheses of Cyclodextrin Derivatives

et al. 2023

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Many scientists are working hard to find green alternatives to classical synthetic methods. Today, state-of-the-art ultrasonic and grinding techniques already drive the production of organic compounds on an industrial scale. The physicochemical and chemical behavior of cyclodextrins often differs from the typical properties of classic organic compounds and carbohydrates. The usually poor solubility and complexing properties of cyclodextrins can require special techniques. By eliminating or reducing the amount of solvent needed, green alternatives can reform classical synthetic methods, making them attractive for environmentally friendly production and the circular economy. The lack of energy-intensive synthetic and purification steps could transform currently inefficient processes into feasible methods. Mechanochemical reaction mechanisms are generally different from normal solution-chemistry mechanisms. The absence of a solvent and the presence of very high local temperatures for microseconds facilitate the synthesis of cyclodextrin derivatives that are impossible or difficult to produce under classical solution-chemistry conditions. Although mechanochemistry does not provide a general solution to all problems, several good examples show that this new technology can open up efficient synthetic pathways.

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Section: Discussionmentioning

confidence: 99%

“…In several cases, although water is an environmentally friendly solvent, its removal is often an energy-intensive or complicated procedure. Moreover, one beneficial feature of the ball mill method is its simple and fast reaction assembly and scalability [ 17 , 20 , 24 , 25 , 26 , 27 ].…”

Section: Introductionmentioning

confidence: 99%

Comparison of the Conventional and Mechanochemical Syntheses of Cyclodextrin Derivatives

et al. 2023

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“…The bead polymer absorbs 4–5 times their weight from water and aqueous solutions (e.g., biological liquids) [ 22 ]. The βCDPIS showed lower swelling due to a more cross-linked structure [ 26 ]. Comparing the swelling capacity of beads, it is less in both 30% ethanol and 10% DMSO than in water; while βCDPIS swelled the most efficiently in 10% DMSO, although there was no high difference in the swelling in the studied solvents.…”

Section: Discussionmentioning

confidence: 99%

“…Briefly at the first step, CD-sodium was formed, then epichlorohydrin cross-linking was performed. Reactions were carried out in a planetary ball mill (Retsch PM100 High Speed Planetary Ball Mill, Retsch GmbH, Haan, Germany), using a 50 mL stainless steel jar and mix of stainless steel balls (m = 44.1 g, in which ø = 5 mm, m = 28.1 g and 550 ø = 1–1.2 mm, m = 16.0 g) at 650 rpm [ 23 , 26 ]. Cyclodextrin microbeads (βCDPB) were made by Cyclolab Ltd. (Budapest, Hungary, Prod.…”

Section: Methodsmentioning

confidence: 99%

Investigation of the Drug Carrier Properties of Insoluble Cyclodextrin Polymer Microspheres

et al. 2022

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The investigation of the usability of solid insoluble β-cyclodextrin polymers (βCDP) in micro-sized, controlled drug delivery systems has only recently attracted interest. Our aim was to form complexes with poorly soluble active pharmaceutical ingredients (APIs) with two types of βCDP for drug delivery applications. Solid insoluble cyclodextrin polymer of irregular shape (βCDPIS) and cyclodextrin microbeads (βCDPB) were used in the experiments. Morphology, surface area, size distribution and swelling capacity of carriers were investigated. We created complexes with two APIs, curcumin and estradiol, and applied powder X-ray diffraction, FTIR and thermal analysis (TGA/DSC) to prove the complexation. Finally, the dissolution, biocompatibility and permeation of APIs on Caco-2 cells were investigated. The size of the beads was larger than 100 µm, their shape was spherical and surfaces were smooth; while the βCDPIS particles were around 4 µm with irregular shape and surface. None of the polymers showed any cytotoxic effect on Caco-2 cells. Both carriers were able to extract curcumin and estradiol from aqueous solutions, and the dissolution test showed prolonged estradiol release. Caco-2 permeability tests were in accordance with the complexation abilities and dissolution of the complexes. This study offers useful data for further pharmaceutical applications of insoluble cyclodextrin polymers.

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“…BM reactions are suitable for the synthesis of SiO 2 /CD composites [91] and chemically stable CD polymers [85,92]. The water and pH more sensitive CD-nanosponge preparations are also an excellent target of the mechanochemical syntheses.…”

Section: Mechanochemical Transformation In Millsmentioning

confidence: 99%

Toward a Greener World—Cyclodextrin Derivatization by Mechanochemistry

Jicsinszky

Cravotto

2021

Molecules

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Cyclodextrin (CD) derivatives are a challenge, mainly due to solubility problems. In many cases, the synthesis of CD derivatives requires high-boiling solvents, whereas the product isolation from the aqueous methods often requires energy-intensive processes. Complex formation faces similar challenges in that it involves interacting materials with conflicting properties. However, many authors also refer to the formation of non-covalent bonds, such as the formation of inclusion complexes or metal–organic networks, as reactions or synthesis, which makes it difficult to classify the technical papers. In many cases, the solubility of both the starting material and the product in the same solvent differs significantly. The sweetest point of mechanochemistry is the reduced demand or complete elimination of solvents from the synthesis. The lack of solvents can make syntheses more economical and greener. The limited molecular movements in solid-state allow the preparation of CD derivatives, which are difficult to produce under solvent reaction conditions. A mechanochemical reaction generally has a higher reagent utilization rate. When the reaction yields a good guest co-product, solvent-free conditions can be slower than in solution conditions. Regioselective syntheses of per-6-amino and alkylthio-CD derivatives or insoluble cyclodextrin polymers and nanosponges are good examples of what a greener technology can offer through solvent-free reaction conditions. In the case of thiolated CD derivatives, the absence of solvents results in significant suppression of the thiol group oxidation, too. The insoluble polymer synthesis is also more efficient when using the same molar ratio of the reagents as the solution reaction. Solid reactants not only reduce the chance of hydrolysis of multifunctional reactants or side reactions, but the spatial proximity of macrocycles also reduces the length of the spacing formed by the crosslinker. The structure of insoluble polymers of the mechanochemical reactions generally is more compact, with fewer and shorter hydrophilic arms than the products of the solution reactions.

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Comparative Studies of Mechanochemically Synthesized Insoluble Beta-Cyclodextrin Polymers

Cited by 5 publications

References 88 publications

Comparison of the Conventional and Mechanochemical Syntheses of Cyclodextrin Derivatives

Comparison of the Conventional and Mechanochemical Syntheses of Cyclodextrin Derivatives

Investigation of the Drug Carrier Properties of Insoluble Cyclodextrin Polymer Microspheres

Toward a Greener World—Cyclodextrin Derivatization by Mechanochemistry

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