Fabrication and in-vitro experimental study on an implantable controlled drug delivery system with micro-hole for zero-order release

Abstract

Drug delivery is essential for effective therapy. Implantable controlled drug delivery systems (ICDDS) have become a research focus due to the associated advantages of continuous, long-duration, sustained delivery and the reduced side effects associated with this form of drug release. ICDDS can be designed to release drugs in accordance with different demands. Zero-order drug release, which involves a theoretically linear relationship between the cumulative amount of released drug and the amount of time taken for the release, is an important drug release rule for the control of chronic diseases. However, the release process is influenced by various parameters and zero-order drug release is therefore difficult to achieve. In this study, to achieve zero-order drug release, an implantable controlled drug delivery system with micro-hole (ICDDSM) was designed and fabricated with degradable polymer. Based on micro electromechanical systems (MEMS) technology, ICDDSM matrixes with circular and honeycomb structures were fabricated using the hot-press shaping method at a temperature of 75 °C, 30 N of force which were maintained for 150 s. A micro-hole with a diameter 100 μm was formed using a femto-second laser. 5-fluorouracil was loaded into the ICDDSM and in-vitro experiments were conducted in 37 °C normal saline solution. The experimental results showed that the 20 mg of loaded 5-fluorouracil was released in 720 h with the relationship between the cumulative amount of released drug and the drug release time tending predominantly toward linearity. Zero-order drug release was thus achieved. This study proposed a new degradable ICDDS structure to achieve zero-order drug release, and the hot-press shaping process proved feasible for the efficient fabrication of the lower-cost polymer structure.