Nanoporous anodic aluminum oxide tube encapsulating a microporous chitosan/collagen composite for long-acting drug release

Abstract

The objective of this study is to develop a long-acting and implantable drug-release device that can effectively control the release rate and concentration of the loaded drug. The proposed device consists of a tubular nanoporous anodic aluminum oxide (AAO) encapsulating a microporous chitosan/collagen composite. The nanopore size of the AAO tube can be modified by adjusting the anodization parameters, which in turn adjust the release rate and concentration, while the microporous chitosan/collagen composite provides the long-acting release feature. Fabrication results indicate that the AAO tube has a uniform pore arrangement with a pore size around 50 nm. The synthesized microporous chitosan/collagen composite containing 90% chitosan yielded the highest moisture content and was therefore used as the drug carrier. Release experiments demonstrate that the proposed long-acting drug release device had released less than 65% of the loading drug on the 17th release day. We then applied the proposed long-acting drug-release scheme as a recombinant human bone morphogenetic-protein 2 (rh-BMP2) release device to induce differentiation of pre-osteoblast MC3T3-E1 cells into osteoblasts. Results from alkaline phosphate and alizarin red S assays demonstrate that the total amount of rh-BMP2 consumed by the proposed AAO tube is much less than that consumed using the conventional culture approach. Furthermore, our approach has the advantage of requiring only one-time dosing, whereas the conventional approach requires the periodic renewal of rh-BMP2. AAO’s one-time dosing feature combined with its biocompatibility and biodegradability can be beneficial in real implant applications.