Cyclodextrin Complexes for Treatment Improvement in Infectious Diseases

Abstract

Infectious diseases are a heterogeneous group of maladies that represent a serious burden to healthcare systems worldwide. Most of the available antimicrobial drugs display poor biopharmaceutical properties that compromise their effectiveness. Cyclodextrins (CDs) are cyclic oligosaccharides of glucopyranose formed by a variable number of repeating units that combine a hydrophilic surface with a hydrophobic cavity. The production of drug/CD complexes has become one of the most extensively investigated technology approaches to improve the stability, solubility, dissolution rate and bioavailability of drugs. The present work overviews the applications of CDs for the formulation of anti-infective agents along with the most relevant administration routes. Finally, an update on the complexes with CDs available on the market to treat infectious diseases is presented.

Nanomaterials and molecular transporters to overcome the bacterial envelope barrier: Towards advanced delivery of antibiotics

“…Cyclodextrins (typically 1.4 to 1.8 nm of outer diameter [117]) are investigated for nearly 70 years as drug carriers to improve the bioavailability, stability and solubility of drugs targeted to mammalian cells [117,118]. The potential of CDs as drug carriers into bacterial cells can be restricted by poor colloidal stability of CDs which may result in the formation of aggregates of tens to hundreds of nanometers [119,122,123,126]. Despite being less colloidaly stable than α-CD and γ-CD, β-CD is by far the most used CD carrier in drug delivery [127].…”

“…Therefore, α-CD would theoretically be a better 'trojan horse' for bacteria than β-CD. However, the narrow 0.47-0.53 nm cavity of α-CD limits the enclosure of most antibiotics [117,119]. Further studies on the structure of CymA's orthologue channels and the transport of different CDs in various bacteria may help elucidate the chances of CDs to penetrate bacteria with associated antibiotics.…”

Development of a Solid Dispersion of Nystatin with Maltodextrin as a Carrier Agent: Improvements in Antifungal Efficacy against Candida spp. Biofilm Infections

“…Semisynthetic derivatives, such as hydroxypropylcellulose or hydroxypropyl methylcellulose, were used with antifungal compounds such as itraconazole, clotrimazole, miconazole, and NYS [ 11 , 16 ]. Moreover, sodium croscarmellose [ 17 ], cyclodextrins [ 9 , 20 ], and maltodextrins (MDs) [ 21 , 22 ] increase the solid dispersion swelling and wettability of different antibiotics during dissolution essays.…”

Self-Assembled Antimicrobial Nanomaterials

“…The need to understand the mechanisms that allow nanomaterials to overcome the bacterial envelopes has been focusing on cyclodextrins, nanoparticles, antimicrobial/cell-penetrating peptides and fusogenic liposomes [ 167 ]; cyclodextrins, for example, form water soluble cyclic oligosaccharides with a hydrophobic cavity that can enclose self-assembled hydrophobic drugs via noncovalent interactions improving delivery and biovailability of drugs targeted to mammalian cells [ 168 ]. The interaction between cationic peptides and the bacterial envelope is initially mediated by non-specific electrostatic interactions with the anionic lipopolysaccharides (LPS) and teichoic acids, in Gram-negative and -positive bacteria, respectively [ 169 , 170 ].…”