A nanostructured porous silicon based drug delivery device

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 growth factors, 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.

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