Real-time and in Situ Drug Release Monitoring from Nanoporous Implants under Dynamic Flow Conditions by Reflectometric Interference Spectroscopy

Abstract

Herein, we present an innovative approach to monitoring in situ drug release under dynamic flow conditions from aluminum implants featuring nanoporous anodic alumina (NAA) covers used as a model of drug-releasing implants. In this method, reflectometric interference spectroscopy (RIfS) is used to monitor in real-time the diffusion of drug from these nanoporous implants. The release process is carried out in a microfluidic device, which makes it possible to analyze drug release under dynamic flow conditions with constant refreshing of eluting medium. This setup mimics the physiological conditions of biological milieu at the implant site inside the host body. The release of a model drug, indomethacin, is established by measuring the optical thickness change with time under four different flow rates (i.e. 0, 10, 30, and 50 μL min(-1)). The obtained data are fitted by a modified Higuchi model, confirming the diffusion-controlled release mechanism. The obtained release rate constants demonstrate that the drug release depends on the flow rate and the faster the flow rate the higher the drug release from the nanoporous covers. In particular, the rate constants increase from 2.23 ± 0.02 to 12.47 ± 0.04 μg min(-1/2) when the flow rate is increased from 10 to 50 μL min(-1), respectively. Therefore, this method provides more reliable and relevant information than conventional in vitro drug release methods performed under static conditions.