Drug Carrier Systems Based on Cyclodextrin Supramolecular Assemblies and Polymers: Present and Perspectives

Abstract

The pharmaceutical applications of cyclodextrins (CDs), cyclic oligosaccharides capable of including hydrophobic molecules inside their cavities, have been known for decades. Besides the solubilising and encapsulating abilities of natural and modified CDs due to the formation of inclusion complexes, there is an increasing interest in organized macrostructures based on CDs as potential drug delivery devices and gene carrier systems. The present review discusses first the case of drug carriers based on monomeric modified CDs (amphiphilic and CD core-star polymers), in which self-assembly plays a major role. Polyrotaxanes, i.e., CDs threaded onto a polymer chain, are then reviewed in relation to their pharmaceutical applications. Finally, covalently linked CDs, either by grafting or crosslinking, are analyzed, including more complex structures formed by assembling CDcontaining networks or chains. We have tried along this review to cover the most recent developments on these structures for drug delivery in a "beyond the cyclodextrin" approach. The review will be helpful, both for readers who want to be introduced into the world of these remarkable structures, or for specialists who are doing research in this field.

Cyclodextrin Based Nanoparticles for Drug Delivery and Theranostics

“…The drug Release rate and amount of drug released from CD functionalized NPs could be affected by preparation method, nature of CD, grafting or crosslinking agents, aqueous solubility of polymer and drug. [102][103][104] The biocompatible supramolecular assembly employing sulfonato-β-CD polysaccharides and CS as building blocks and different physiological pH as controlling method explored by for controlled release of berberine. The sulfonato-β-CD based carrier loaded with natural molecule berberine, allows drug release at intestinal pH and shows stability in the gastric environment.…”

Pseudo-Polyrotaxanes of Cyclodextrins with Direct and Reverse X-Shaped Block Copolymers: A Kinetic and Structural Study

“…19 The synthesis, characterization and mechanism of threading of PRs and PPRs based on CDs and different polymers, have been extensively reviewed in the literature, 2,3,20 as well as their potential applications in biomedicine, particularly in drug delivery, or biomaterials, such as hydrogels and scaffolds in tissue engineering. 9,10,[21][22][23] The first PPR based on CDs was reported by Harada in 1990, 24 and obtained from the complexation of PEG and α-CD in water, with a composition of 2 ethylene oxide (EO) units per CD. Harada also established that the binding is very selective, depending on the type of CD and monomer: 1,24,25 α-CD only forms stable inclusion complexes with PEG, while the threading does not occur with polypropylene glycol (PPG); instead, β-and γ-CD form PPRs with PPG but not with PEG.…”

Poly(methyl vinyl ether-co-maleic acid) Hydrogels Containing Cyclodextrins and Tween 85 for Potential Application as Hydrophobic Drug Delivery Systems

“…Surfactants provide micellar and/or hydrophobic domains within the hydrogel structure, thus, improving the loading of hydrophobic drugs (20). Another approach to improve hydrogel compatibility with hydrophobic drugs is the incorporation of molecules which have the ability to form inclusion complexes, such as cyclodextrins (CDs) (18,21). CDs are cyclic oligosaccharides formed by 6, 7 or 8 dextrose units (α, β and γ-CD respectively), which have a truncated cone structure with a hydrophilic outer surface and a hydrophobic inner cavity (21)(22)(23)(24).…”

“…Another approach to improve hydrogel compatibility with hydrophobic drugs is the incorporation of molecules which have the ability to form inclusion complexes, such as cyclodextrins (CDs) (18,21). CDs are cyclic oligosaccharides formed by 6, 7 or 8 dextrose units (α, β and γ-CD respectively), which have a truncated cone structure with a hydrophilic outer surface and a hydrophobic inner cavity (21)(22)(23)(24). The hydrophobic cavity has the ability to host hydrophobic molecules, which results in the formation of an inclusion complex (21)(22)(23).…”

“…CDs are cyclic oligosaccharides formed by 6, 7 or 8 dextrose units (α, β and γ-CD respectively), which have a truncated cone structure with a hydrophilic outer surface and a hydrophobic inner cavity (21)(22)(23)(24). The hydrophobic cavity has the ability to host hydrophobic molecules, which results in the formation of an inclusion complex (21)(22)(23). In the present work, a simple solvent-free strategy to prepare hydrogels containing cyclodextrins and/or surfactants is described.…”