Cyclodextrin Complexation for Affinity‐Based Antibiotic Delivery

Abstract

Novel beta-cyclodextrin polymer (CD)-based drug delivery hydrogels were prepared by varying type and concentration of crosslinkers and optimizing the gel synthesis conditions. For comparison, dextrose gels were prepared using the same crosslinkers. The optimized gels were characterized by Fourier Transform Infrared (FTIR), Scanning Electron Microscopy (SEM), and X-ray diffraction (XRD) as well as swelling and release studies. For drug release studies, the gels were loaded with three different model antibiotics varying in size and hydrophobicity: rifampin (RM), novobiocin (NB), and vancomycin (VM), using a common solvent method. The loading efficiency was calculated and release kinetics were determined in vitro. As expected for affinity-based mechanisms, the release of drugs, from CD-based gels, was slower than release from dextrose gels which indicated that the antibiotics all form inclusion complexes with CD. Release kinetics were also more linear in the observed time frame when using CD-based hydrogels versus dextrose hydrogels. This modification in release depended on the affinity-between CD and drug, such that larger drugs and more hydrophilic ones had their release profiles altered less than small hydrophobic ones. In conclusion, affinity-based mechanisms can be used to load antibiotics and obtain longer, more linear release profiles than purely diffusion-based mechanisms.

Affinity‐Based Drug Delivery

“…When coated on biomaterial surfaces, their b-CD system antibiotics more consistently in zones of bacterial inhibition, thus confirming bioactivity of the delivery antibiotic. [100,101] Meanwhile, the Hildebrand and coworkers synthesized a crosslinked hydroxypropyl-b-CD (HPb-CD) with citric acid and formed a CD polymer through an esterification reaction. The HPb-CD polymer-coated prostheses demonstrated higher drug loading and better release of Rifampin, Vancomcyin, and Ciprofloxacin than non-CD controls.…”

Experimental Studies and Modeling of Drug Release from a Tunable Affinity-Based Drug Delivery Platform

“…11,[21][22][23] Affinity can be described as the tendency for one molecule to bind to another. Affinitybased systems utilize the molecular interaction between the therapeutic agent and the delivery vehicle.…”

Featured Article: Chemotherapeutic delivery using pH-responsive, affinity-based release

“…27,28 Briefly, 1 g of dried pCD or pDextran was dissolved in 4 mL dimethylformamide (pCD) or dimethylsulfoxide (pDextran), cross-linked, cured at 70 C for 45 min (pCD) or 120 min (pDextran), and punched into 8 mm disks. All disks were washed in solutions of 100% solvent, 50:50 solvent:water, and 100% water over several days.…”

“…This is consistent with previous observations that more drug can be loaded into affinity-based polymers than their non-affinity controls. 27,28 Specifically, we calculated that the average mass loaded into each pDextran disk was approximately 103 AE 45 mg AD-DOX/mg polymer and the average mass loaded into Figure 5 Cumulative release studies show AD-DOX release is dependent on pH change. Due to the added affinity from the AD group, release from pCD polymers was shown to be very slow, with virtually no burst.…”

“…Soluble CD is routinely used to increase the solubility of hydrophobic drugs. [27][28][29] We turn that observation on its head by making insoluble forms of CD (CD polymers or pCD) to entrap rather than solubilize drug. With these CD polymers, we then show high loading levels and slow, sustained release of many different drugs.…”