Pseudopolyrotaxane Formation in the Synthesis of Cyclodextrin Polymers: Effects on Drug Delivery, Mechanics, and Cell Compatibility

Abstract

Numerous groups have reported the use of cyclodextrin (CD)-based polymers for drug delivery applications due to their capacity to form inclusions with small molecule drugs, delaying the rate of drug release beyond that of diffusion alone (termed "affinity-based" drug delivery). Herein we demonstrate synthesis and characterization of a new family of CD-based polymers, some as pseudopolyrotaxanes, generated under mild (aqueous, room temperature) conditions. The formation of these new affinity polymers results in broad mechanical properties. Three diglycidylether cross-linkers which vary in length from 0 to 10 ethylene glycol units were examined. Pseudopolyrotaxane formation was found only with the highest-length cross-linker, noted first by a sharp change in both material properties and then confirmed by chemical signature. Materials were thoroughly evaluated by NMR, DSC, DMA, TGA, XRD, and FTIR. Cross-linker choice was also tested for impact on drug loading and delivery capacity, using antibiotics as model drugs. Chemically similar polymers without showing affinity rapidly saturated in loading experiments, while affinity materials showing high capacity for drug loading, even beyond the solubility limit of the drugs. When using the polymers with these new cross-linkers, affinity-based drug delivery is maintained: the materials are capable of antibiotic delivery, and clearance of Staphylococcus aureus, at least an order of magnitude better than diffusion-only control polymers. In cell compatibility studies, CD-based polymers were shown to have low overt cell toxicity and even resisted cell adhesion, presumably due to their highly hydrated state.

Injectable, Self-Healing Chimeric Catechol-Fe(III) Hydrogel for Localized Combination Cancer Therapy

“…High entrapment efficency of hydrophobic and hydrophilic drugs along with their superior efficacy has been demonstrated in many polymeric hydrogels based on covalent , or noncovalent cross-linking approaches. , However, hydrogels derived from noncovalent interactions exhibit poor mechanics, limited drug encapsulation efficacy, slow self-healing property, and burst drug release. , In contrast, the undesirable irreversible nature and poor scalable synthesis of covalently cross-linked hydrogels limit their biomedical utility . Hydrophilic PEG (polyethylene glycol) monomers were copolymerized with hydrophobic monomers such as lactic acid or glutamic acid to achieve amphiphilic hydrogels. , A triblock copolymer PEG-PCL-PEG copolymer (PCL = poly­(ε-caprolactone)) was used to produce thermoresponsive hydrogels for delivery of Honokiol nanoparticles for anticancer therapy .…”

“…Hydrogels derived from small molecules or polymers are emerging as modular scaffolds for localized drug delivery, 10,11 gene therapy, 12,13 antimicrobial therapy, 14,15 and tissue engineering 16 applications as their mechanical properties can be easily tuned for specific application. 17 High entrapment efficency of hydrophobic and hydrophilic drugs along with their superior efficacy has been demonstrated in many polymeric hydrogels based on covalent 18,19 or noncovalent cross-linking approaches. 20,21 However, hydrogels derived from noncovalent interactions exhibit poor mechanics, limited drug encapsulation efficacy, slow self-healing property, and burst drug release.…”

Cyclodextrin-Modified Nanomaterials for Drug Delivery: Classification and Advances in Controlled Release and Bioavailability

“…However, the study of CD-based polymeric derivatives is not only limited to the use of epichlorohydrin; new derivatives using novel crosslinking agents have also been investigated. An interesting synthesis using diglycidylether as a crosslinker and HPβCD was investigated by Thatiparti and collaborators [103]. Polymers made with crosslinkers of different chain lengths showed better mechanical and physicochemical properties, such as improved stability concerning other similar systems, as well as a different loading capacity.…”

Cyclodextrin polymer coatings resist protein fouling, mammalian cell adhesion, and bacterial attachment

“…Prior literature corroborates this observation 98 . Furthermore, while certain CD-based polymers can be made optically transparent 99 , the translucent PP substrates and CD polyurethane coatings in this study were not optimized for cell observation.…”