Doxycycline release from cyclodextrin oligomer-containing collagen gels

This paper tests the hypothesis that oligomers of cyclodextrin small enough to remain soluble under aqueous conditions can be incorporated in a collagen gel during fibrillogenesis in a way that enhances prolonged release of a therapeutic. Native D-banded collagen fibril hydrogels are used as an intentionally fast-releasing matrix to examine how affinity-based interactions delay drug release. Doxycycline loading and release from a collagen hydrogel containing entrapped oligomers of γ-cyclodextrin (CD) is investigated. Mathematical modeling is used to separate the effects of the collagen matrix from the incorporated CD. Incorporating CD oligomers increased the releasable amount of doxycycline by 220% and reduced its release rate fivefold. These results demonstrate that affinity-based material design can substantially shift release kinetics even in diffusion-dominated systems. Use of this system to treat chronic peri-implantitis arising from infection and inflammation at the abutment/gingiva interface in dental implants is discussed. Current treatment strategies involve frequent administration of systemic antibiotics and collagenase inhibitors which complicates clinical management. Longer-acting local delivery, even over modest timescales, could reduce dosing frequency and reduce unwanted side effects, thus improving treatment efficacy. A localized controlled drug-release approach may offer a way to simplify this clinical management.