Cyclodextrins: A Weapon in the Fight Against Antimicrobial Resistance

Abstract

Antimicrobial resistance poses one of the most serious global challenges of our age. Cyclodextrins (CDs) are widely utilized excipients in formulations because of their solubilizing properties, low toxicity, and low in°ammatory response. This review summarizes recent investigations of antimicrobial agents involving CDs and CD-based antimicrobial materials. CDs have been employed for antimicrobial applications either through formation of inclusion complexes or by chemical modi¯cation of their hydroxyl groups to tailor pharmaceutically active compounds. Applications of these CD inclusion complexes include drug delivery, antimicrobial coatings on materials (e.g., biomedical devices and implants) and antimicrobial dressings that help to prevent wound infections. There are relatively limited studies of chemically modi¯ed CDs with antimicrobial activity. The mechanism of action of antimicrobial CD inclusion complexes and derivatives needs further elucidation, but activity of CDs and their derivatives is often associated with their interaction with bacterial cell membranes.

Azo group(s) in selected macrocyclic compounds

“…The versatile career of CDs is due to their availability, biocompatibility, biodegradability and industrial scale production. That is why complexes of CDs with various molecules have found multitude applications in many branches of science and industry, for example: in supramolecular polymers [ 226 – 228 ], hydrogels [ 229 ], bioactive materials [ 230 ], drug delivery [ 231 – 234 ], dynamic materials [ 235 ], catalysis [ 236 ] and separation methods [ 237 – 239 ]. Substituted cyclodextrins give the possibility of the more specific modification of different type of substrates, molecules and surfaces [ 240 ], changing their physical and chemical properties, which opens the way to the new applications of such hopeful systems [ 241 ].…”

Cyclodextrin Inclusion Complexes with Antibiotics and Antibacterial Agents as Drug-Delivery Systems—A Pharmaceutical Perspective

“…We expect that such an approach will be desirable in the context of antibiotics, as approved antibiotics gradually lose their activity as a result of an increase in the number of drug-resistant bacteria, and simultaneously a small number of new drugs enter clinical practice. To the best of our knowledge, no comprehensive summary of antibacterial drug complexation with CDs has been published so far and only selected examples of antibacterial drug/CD complexes are provided in the available review articles [ 11 , 12 ]. Reports of CD complexes of antibiotics from nearly all classes are discussed in this article, ranging from pioneering works to significant articles published online by the end of 2021.…”

“…Due to the growing drug resistance among bacteria, it is very important to increase antimicrobial efficacy, which can occur through the spontaneous formation of hydrogen bonds between CDs and several components of the bacterial cell membrane [ 32 ]. Hence, complexation with CDs enables antibiotics to be used in much lower concentrations, thus reducing exposure to the antibiotic, which in turn delays the onset of antibiotic resistance [ 12 , 33 , 34 ]. A recent study correlated antimicrobial activity with the hydrophobicity/hydrophilicity balance of polyalkylamino CDs [ 35 ].…”

Development of a ternary cyclodextrin–arginine–ciprofloxacin antimicrobial complex with enhanced stability

“…A simple and very effective approach to redesigning old antibiotics includes the formation of instable complexes that modify properties such as solubility, stability, bioavailability, and permeability, thereby directly influencing their therapeutic outcome. In that context, cyclodextrins (CDs) are particularly applicable 11 , 12 . With a truncated cone structure, they have a hydrophilic shell (with 7 primary groups oriented toward the narrow edge and 14 secondary sugar hydroxyl groups oriented toward the wider edge of the cone, in the case of β-CD) and a hydrophobic core (with a carbon backbone of 7 glucopyranose units that make up the structure of β-CD) available for interactions with drug molecules 11 , 13 , 14 .…”

“…In that context, cyclodextrins (CDs) are particularly applicable 11 , 12 . With a truncated cone structure, they have a hydrophilic shell (with 7 primary groups oriented toward the narrow edge and 14 secondary sugar hydroxyl groups oriented toward the wider edge of the cone, in the case of β-CD) and a hydrophobic core (with a carbon backbone of 7 glucopyranose units that make up the structure of β-CD) available for interactions with drug molecules 11 , 13 , 14 . Most commonly, antibiotics are formulated as inclusion complexes when the hydrophobic part of the drug interacts with the hydrophobic inner core area of the CD, which consequently increases its solubility by several times 11 .…”