Steven J. P. McInnes

Stimulus-Responsiveness and Drug Release from Porous Silicon Films ATRP-Grafted with Poly(N-isopropylacrylamide)

In this report, we employ surface-initiated atom transfer radical polymerization (SI-ATRP) to graft a thermoresponsive polymer, poly(N-isopropylacrylamide) (PNIPAM), of controlled thickness from porous silicon (pSi) films to produce a stimulus-responsive inorganic-organic composite material. The optical properties of this material are studied using interferometric reflectance spectroscopy (IRS) above and below the lower critical solution temperature (LCST) of the PNIPAM graft polymer with regard to variation of pore sizes and thickness of the pSi layer (using discrete samples and pSi gradients) and also the thickness of the PNIPAM coatings. Our investigations of the composites thermal switching properties show that pore size, pSi layer thickness, and PNIPAM coating thickness critically influence the materials thermoresponsiveness. This composite material has considerable potential for a range of applications including temperature sensors and feedback controlled drug release. Indeed, we demonstrate that modulation of the temperature around the LCST significantly alters the rate of release of the fluorescent anticancer drug camptothecin from the pSi-PNIPAM composite films.

Nanoporous anodic aluminium oxide membranes with layered surface chemistry

A new and facile method is described to prepare Janus-like nanoporous anodic aluminium oxide (AAO) membranes with distinctly different internal and external surface chemistry.

Combination of iCVD and porous silicon for the development of a controlled drug delivery system.

We describe a pH responsive drug delivery system which was fabricated using a novel approach to functionalize biodegradeable porous silicon (pSi) by initiated chemical vapor deposition (iCVD). The assembly involved first loading a model drug (camptothecin, CPT) into the pores of the pSi matrix followed by capping the pores with a thin pH responsive copolymer film of poly(methacrylic acid-co-ethylene dimethacrylate) (p(MAA-co-EDMA)) via iCVD. Release of CPT from uncoated pSi was identical in two buffers at pH 1.8 and pH 7.4. In contrast, the linear release rate of CPT from the pSi matrix with the p(MAA-co-EDMA) coating was dependent on the pH; release of CPT was more than four times faster at pH 7.4 (13.1 nmol/(cm(2) h)) than at pH 1.8 (3.0 nmol/(cm(2) h)). The key advantage of this drug delivery approach over existing ones based on pSi is that the iCVD coating can be applied to the pSi matrix after drug loading without degradation of the drug because the process does not expose the drug to harmful solvents or high temperatures and is independent of the surface chemistry and pore size of the nanoporous matrix.

New biodegradable materials produced by ring opening polymerisation of poly(l-lactide) on porous silicon substrates

In this paper, we describe for the first time the preparation of biodegradable inorganic/organic hybrid materials by grafting poly(L-lactide) (PLLA) from porous silicon (pSi) films and microparticles. To graft a PLLA layer from pSi, tin(II) 2-ethylhexanoate catalysed ring opening polymerisation was performed using pSi surface-bound hydroxyl groups as initiators. Chemical surface characterisation by means of diffuse reflectance infrared spectroscopy, X-ray photoelectron spectroscopy and water contact angle measurements confirmed the presence of the PLLA film. Furthermore, atomic force microscopy demonstrated the formation of PLLA nanobrushes on the pSi surface. We also ascertained by interferometric reflectance spectroscopy that the PLLA layer successfully slowed down the corrosion of the porous silicon layer in aqueous medium. Finally, thermal gravimetric analysis showed weight loss transitions that closely resemble the expected decomposition peak for low molecular weight PLLA. We believe that biodegradable hybrid materials like the ones presented here will find uses in tissue engineering and drug delivery, for example in applications where complex degradation profiles are required that cannot be achieved with one type of material alone.

Fabrication and Characterization of a Porous Silicon Drug Delivery System with an Initiated Chemical Vapor Deposition Temperature-Responsive Coating

This paper reports on the fabrication of a pSi-based drug delivery system, functionalized with an initiated chemical vapor deposition (iCVD) polymer film, for the sustainable and temperature-dependent delivery of drugs. The devices were prepared by loading biodegradable porous silicon (pSi) with a fluorescent anticancer drug camptothecin (CPT) and coating the surface with temperature-responsive poly(N-isopropylacrylamide-co-diethylene glycol divinyl ether) (pNIPAM-co-DEGDVE) or non-stimulus-responsive poly(aminostyrene) (pAS) via iCVD. CPT released from the uncoated oxidized pSi control with a burst release fashion (∼21 nmol/(cm(2) h)), and this was almost identical at temperatures both above (37 °C) and below (25 °C) the lower critical solution temperature (LCST) of the switchable polymer used, pNIPAM-co-DEGDVE (28.5 °C). In comparison, the burst release rate from the pSi-pNIPAM-co-DEGDVE sample was substantially slower at 6.12 and 9.19 nmol/(cm(2) h) at 25 and 37 °C, respectively. The final amount of CPT released over 16 h was 10% higher at 37 °C compared to 25 °C for pSi coated with pNIPAM-co-DEGDVE (46.29% vs 35.67%), indicating that this material can be used to deliver drugs on-demand at elevated temperatures. pSi coated with pAS also displayed sustainable drug delivery profiles, but these were independent of the release temperature. These data show that sustainable and temperature-responsive delivery systems can be produced by functionalization of pSi with iCVD polymer films. Benefits of the iCVD approach include the application of the iCVD coating after drug loading without causing degradation of the drug commonly caused by exposure to factors such as solvents or high temperatures. Importantly, the iCVD process is applicable to a wide array of surfaces as the process is independent of the surface chemistry and pore size of the nanoporous matrix being coated.

Surface engineering of porous silicon to optimise therapeutic antibody loading and release

The proinflammatory cytokine, tumor necrosis factor-α (TNF-α), is elevated in several diseases such as uveitis, rheumatoid arthritis and non-healing chronic wounds. Adding Infliximab, a chimeric IgG1 monoclonal antibody raised against TNF-α, to chronic wound fluid can neutralise human TNF-α, thereby providing a potential therapeutic option for chronic wound healing. However, to avoid the need for repeated application in a clinical setting, and to protect the therapeutic antibody from the hostile environment of the wound, suitable delivery vehicles are required. Porous silicon (pSi) is a biodegradable high surface area material commonly employed for drug delivery applications. In this study, the use of pSi microparticles (pSi MPs) for the controlled release of Infliximab to disease environments, such as chronic wounds, is demonstrated. Surface chemistry and pore parameters for Infliximab loading are first optimised in pSi films and loading conditions are transferred to pSi MPs. Loading regimens exceeding 60 μg of Infliximab per mg of pSi are achieved. Infliximab is released with zero-order release kinetics over the course of 8 days. Critically, the released antibody remains functional and is able to sequester TNF-α over a weeklong timeframe; suitable for a clinical application in chronic wound therapy.

Porous silicon-based nanostructured microparticles as degradable supports for solid-phase synthesis and release of oligonucleotides.

We describe the preparation of several types of porous silicon (pSi) microparticles as supports for the solid-phase synthesis of oligonucleotides. The first of these supports facilitates oligonucleotide release from the nanostructured support during the oligonucleotide deprotection step, while the second type of support is able to withstand the cleavage and deprotection of the oligonucleotides post synthesis and subsequently dissolve at physiological conditions (pH = 7.4, 37°C), slowly releasing the oligonucleotides. Our approach involves the fabrication of pSi microparticles and their functionalisation via hydrosilylation reactions to generate a dimethoxytrityl-protected alcohol on the pSi surface as an initiation point for the synthesis of short oligonucleotides.

Porous silicon nanoparticles as a nanophotocathode for photoelectrochemical water splitting

The antireflective properties and nanometer sizes of silicon nanoparticles can be exploited for improved solar energy conversion. We report on using porous silicon nanoparticles as a photocathode for photoelectrochemical water splitting. An enhancement in the photocurrent density was observed when porous silicon nanoparticles were decorated with indium phosphide nanocrystals and a bio-inspired iron sulfur carbonyl electrocatalyst. Our system gave a photocurrent density of −2.2 μA cm−2 while generating hydrogen gas.

Lateral heterogeneities in supported bilayers from pure and mixed phosphatidylethanolamine demonstrating hydrogen bonding capacity.

The phase behavior and lateral organization of saturated phosphatidylethanolamine (PE) and phosphatidylcholine (PC) bilayers were investigated using atomic force microscopy (AFM) and force-volume (FV) imaging for both pure and two component mixed layers. The results demonstrated the existence of unexpected segregated domains in pure PE membranes at temperatures well below the transition temperature (Tm) of the component phospholipid. These domains were of low mechanical stability and lacked the capacity for hydrogen bonding between lipid headgroups. Temperature dependent studies for different PC/PE ratios using AFM also demonstrated the mixing of these phospholipid bilayers to exhibit only a single gel to liquid transition temperature. Further work performed using FV imaging and chemically modified probes established that no lipid segregation exists at the PC/PE ratios investigated.

Delivery of Flightless I Neutralizing Antibody from Porous Silicon Nanoparticles Improves Wound Healing in Diabetic Mice

&NA; Flightless I (Flii) is elevated in human chronic wounds and is a negative regulator of wound repair. Decreasing its activity improves healing responses. Flii neutralizing antibodies (FnAbs) decrease Flii activity in vivo and hold significant promise as healing agents. However, to avoid the need for repeated application in a clinical setting and to protect the therapeutic antibody from the hostile environment of the wound, suitable delivery vehicles are required. In this study, the use of porous silicon nanoparticles (pSi NPs) is demonstrated for the controlled release of FnAb to diabetic wounds. We achieve FnAb loading regimens exceeding 250 µg antibody per mg of vehicle. FnAb‐loaded pSi NPs increase keratinocyte proliferation and enhance migration in scratch wound assays. Release studies confirm the functionality of the FnAb in terms of Flii binding. Using a streptozotocin‐induced model of diabetic wound healing, a significant improvement in healing is observed for mice treated with FnAb‐loaded pSi NPs compared to controls, including FnAb alone. FnAb‐loaded pSi NPs treated with proteases show intact and functional antibody for up to 7 d post‐treatment, suggesting protection of the antibodies from proteolytic degradation in wound fluid. pSi NPs may therefore enable new therapeutic approaches for the treatment of diabetic ulcers. &NA; Flightless neutralizing antibody (FnAb) is packaged into porous silicon nanoparticles (pSi NPs), protecting the drug from the harsh diabetic wound environment. pSi NPs have a high antibody‐loading capacity, extend antibody release, and critically retain antibody functionality. The application of FnAb‐loaded pSi NPs to diabetic wounds in mice leads to significant improvements in healing compared to wounds treated with FnAb alone. Figure. No caption available.