A nanostructured porous silicon based drug delivery device

Description/Abstract

Targeted and controlled delivery of therapeutic agents on demand is pivotal in realising the efficacy of many pharmaceuticals. The design and fabrication of a novel, electrically-addressable, porous structure-based drug delivery device for the controlled release of therapeutic proteins and peptides, are described in this thesis.

The initial prototype microdevice design incorporates a porous polysilicon (PPSi) structure as a drug reservoir. Two alternative methods were investigated to fabricate the PPSi structure: i) the chemical stain etching method; ii) a reactive ion etching (RIE) method through a masking template. Random pores, with irregular pore shape and size in the micro- to mesoporous regime (< 50 nm), were obtained using the stain etching method but this method suffered from poor reproducibility and non-uniformity. Two novel RIE approaches were investigated to fabricate ordered PPSi structures; two different masking templates were investigated – a porous anodic alumina (PAA) and a metal mask with hexagonally arranged holes produced by a novel nanosphere lithography (NSL) technique. A quasi-ordered PAA template with pore diameters in the region of 50 nm was fabricated but was not suitable for the subsequent proposed RIE process. By using the NSL technique, quasi-ordered PPSi structures with tapered pore profiles, were obtained. This is the first demonstration of the fabrication of PPSi with ordered pores of sizes in the macropore range of ~ 370 nm.

A revised silicon-based prototype microdevice was designed and fabricated. The microdevice incorporates a nanostructured, quasi-ordered porous silicon (PSi) as a drug reservoir and an integrated heater and temperature sensor as an active control mechanism. The PSi structure was fabricated using a modified NSL technique and a Bosch-based RIE process. Hexagonally arranged cylindrical pores with diameters between ~75 nm and ~120 nm, and depths in the range of ~330 nm and 500 nm, were obtained. The novel fabrication techniques investigated here are simple and versatile; both p-type and n-type PSi structures have been successfully fabricated.

Proof-of-concept studies, using the revised prototype drug delivery microdevices, suggested that the nanostructured PSi would be suitable for the passive release of an intermediate-sized (~23 000 Dalton) model protein. It is envisaged that the microdevice has the potential to deliver osteoinductive growthfactors, on demand, to the site of fracture, in a controlled and sustainable manner, as a first step to an intelligent therapeutic system for skeletal regeneration.