Polymeric micelles in porous and nanotubular implants as a new system for extended delivery of poorly soluble drugs

Abstract

Nanopore and nanotube structures such as anodic aluminium oxide (AAO) and nanotubular titania (TNT) prepared by self-ordering electrochemical anodization have attracted considerable attention for the development of new implant devices and drug delivery applications. In this work, we present a new implantable drug delivery system that integrates polymer micelles as drug nanocarrier and nanoporous structure to achieve an extended delivery of poorly water soluble drugs. Two strategies for controlled release of nanocarriers from AAO and TNT platforms were explored: (i) the influence of pore diameters of AAO (65 nm to 160 nm) and nanocarrier diameters (15–75 nm) and (ii) application of thin film-plasma polymer layer on the surface of porous material. By varying pore and polymer micelles diameters a two-phase release kinetics with burst release of 31–55% in the first 6–8 h followed by the slow phase, spanning across 8–22 days were obtained. Nevertheless, although results were improved by varying pore diameters, it is still not the optimal strategy to achieve a slow release of drug nanocarriers from porous platforms. More effective method to achieve their extended release with zero-order kinetics was demonstrated using plasma polymerisation method, in which complete release of micelles was found to be delayed to 27–31 days, with a significantly lowered burst release (12–15%).