Development andIn VitroCharacterization of Hyaluronic Acid-Based Coatings for Implant-Associated Local Drug Delivery Systems

Svea Petersen,Klaus-Peter Schmitz,Sebastian Kaule,Michael Teske,Ingo Minrath,Katrin Sternberg

doi:10.1155/2013/587875

Abstract

The development of drug-eluting coatings based on hyaluronic acid (HA) is especially promising for implant-associated local drug delivery (LDD) systems, whose implantation provokes high insertion forces, as, for instance, cochlear implants or drug-coated balloons (DCB). The lubricious character of HA can then reduce the coefficient of friction and serve as drug reservoir simultaneously. In this context, we investigated several plasma- and wet-chemical methods for the deposition of HA-based coatings with LDD function on polyamide 12 as a model implant surface, conventionally used for DCB. In contrast to aminosilane, epoxy silane surface layers allowed the covalent attachment of a smooth and uniform HA base layer, which provided good adherence of further HA layers deposited by manual dip coating at a subsequent processing stage. The applied HA-crosslinking procedure during dip coating influences the transfer and release of paclitaxel, which could be reproducibly incorporated via infiltration. While crosslinking with N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride provided HA coatings on DCB, which allowed for an efficient paclitaxel transfer upon expansion in a vessel model, crosslinking with glutardialdehyde resulted in a slower drug release being more appropriate for implants with longer residence time in the body. The developed HA coating is hence well suited for spontaneous and sustained LDD.

Highlights

Polymers have found applications in diverse biomedical fields such as tissue engineering, cardiovascular intervention, ophthalmology, dentistry, and bone repair [1]
Contact angle measurements were performed in order to evaluate surface changes and the resulting hydrophilic/hydrophobic character after silanization via APTES and GPTMS and attachment of the hyaluronic acid (HA) base layer
The contact angles decreased to 73 ± 7∘ for unmodified, 70 ± 8∘ for APTES-modified and 50 ± 10∘ for GPTMS-modified polyamide 12 (PA12) surfaces (Table 1)

Summary

Introduction

Polymers have found applications in diverse biomedical fields such as tissue engineering, cardiovascular intervention, ophthalmology, dentistry, and bone repair [1]. While principally used polymers for LDD systems are relatively hydrophobic as exemplified by the commonly used biocompatible and biodegradable polylactide [3,4,5], which allows for a sustained drug release over a long time period, swellable hydrophilic implant coatings are more likely used with the purpose to reduce insertion forces. These coatings are for instance applied to angioplasty catheters for reduction of the coefficient of friction during transfer to the stenotic vessel [6]. The demand can be underlined by the fact that commercially available DCB surface designs often involve water soluble additives [9, 10], which might lead to considerable drug losses during the transit of the device through the vascular system [11, 12]

Results

Discussion

Conclusion