Jennifer S. Andrew

Real-time monitoring of sustained drug release using the optical properties of porous silicon photonic crystal particles

A controlled and observable drug delivery system that enables long-term local drug administration is reported. Biodegradable and biocompatible drug-loaded porous Si microparticles were prepared from silicon wafers, resulting in a porous 1-dimensional photonic crystal (rugate filter) approx. 12 μm thick and 35 μm across. An organic linker, 1-undecylenic acid, was attached to the Si-H terminated inner surface of the particles by hydrosilylation and the anthracycline drug daunorubicin was bound to the carboxy terminus of the linker. Degradation of the porous Si matrix in vitro was found to release the drug in a linear and sustained fashion for 30 d. The bioactivity of the released daunorubicin was verified on retinal pigment epithelial (RPE) cells. The degradation/drug delivery process was monitored in situ by digital imaging or spectroscopic measurement of the photonic resonance reflected from the nanostructured particles, and a simple linear correlation between observed wavelength and drug release was observed. Changes in the optical reflectance spectrum were sufficiently large to be visible as a distinctive red to green color change.

Enhanced Magnetic Resonance Contrast of Fe3O4 Nanoparticles Trapped in a Porous Silicon Nanoparticle Host

Magnetic nanoparticles have been investigated for a broad range of clinical and diagnostic applications including immunoassays, targeted drug delivery, magnetic resonance imaging (MRI), and magnetic hyperthermia.[1–4] One of the earliest clinical applications of magnetic nanoparticles was the use of superparamagnetic iron oxide to enhance image contrast in MRI,[5–8] due to the ability of these nanoparticles to increase proton relaxation rates. Coating of superparamagnetic iron oxide nanoparticles (SPIONs) with dextran provides a non-toxic and non-immunogenic material that circulates effectively in the body, allowing enhanced imaging of liver, spleen and lymphatic tissues. These particles are used clinically to deliniate hepatic lesions in patients with cirrohis or hepatocellular carcinoma (HCC) and to identify lymph node metastases.[5, 9] The superparamagnetic materials are sequestered within Kupffer cells, whose function is to recycle iron from non-viable red blood cells. Malignant HCC tissues lack functional Kupffer cells, resulting in reduced uptake of the nanoparticles compared to healthy tissue. More recently, methods have been developed that allow SPIONs to aid in the detection of solid tumors.[9–15]

Enzyme-Responsive Hydrogel Microparticles for Pulmonary Drug Delivery

Poly(ethylene glycol) based hydrogel microparticles were developed for pulmonary drug delivery. Hydrogels are particularly attractive for pulmonary delivery because they can be size engineered for delivery into the bronchi, yet also swell upon reaching their destination to avoid uptake and clearance by alveolar macrophages. To develop enzyme-responsive hydrogel microparticles for pulmonary delivery a new synthesis method based on a solution polymerization was developed. This method produces spherical poly(ethylene glycol) (PEG) microparticles from high molecular weight poly(ethylene glycol) diacrylate (PEGDA)-based precursors that incorporate peptides in the polymer chain. Specifically, we have synthesized hydrogel microparticles that degrade in response to matrix metalloproteinases that are overexpressed in pulmonary diseases. Small hydrogel microparticles with sizes suitable for lung delivery by inhalation were obtained from solid precursors when PEGDA was dissolved in water at a high concentration. The average diameter of the particles was between 2.8 and 4 μm, depending on the molecular weight of the precursor polymer used and its concentration in water. The relation between the physical properties of the particles and their enzymatic degradation is also reported, where an increased mesh size corresponds to increased degradation.

A route to synthesize multifunctional tri-phasic nanofibers

Nanofibers hold enormous potential for novel nanomaterials due to their ease of fabrication, yet fabrication routes are primarily used to produce bilayer structures. This paper describes a novel process for producing tri-layer ceramic composite fibers, and presents a proof of concept in the form of a multilayer multiferroic nanofiber consisting of alternating ferroelectric and ferromagnetic phases.

Size Control of Porous Silicon-Based Nanoparticles via Pore-Wall Thinning

Photoluminescent silicon nanocrystals are very attractive for biomedical and electronic applications. Here a new process is presented to synthesize photoluminescent silicon nanocrystals with diameters smaller than 6 nm from a porous silicon template. These nanoparticles are formed using a pore-wall thinning approach, where the as-etched porous silicon layer is partially oxidized to silica, which is dissolved by a hydrofluoric acid solution, decreasing the pore-wall thickness. This decrease in pore-wall thickness leads to a corresponding decrease in the size of the nanocrystals that make up the pore walls, resulting in the formation of smaller nanoparticles during sonication of the porous silicon. Particle diameters were measured using dynamic light scattering, and these values were compared with the nanocrystallite size within the pore wall as determined from X-ray diffraction. Additionally, an increase in the quantum confinement effect is observed for these particles through an increase in the photoluminescence intensity of the nanoparticles compared with the as-etched nanoparticles, without the need for a further activation step by oxidation after synthesis.

Matrix metalloproteinase-sensitive hydrogel microparticles for pulmonary drug delivery of small molecule drugs or proteins

Hydrogel microparticles are particularly attractive for pulmonary drug delivery. Their size can be engineered for efficient delivery into the bronchi, where they subsequently swell, avoiding macrophage uptake. In this study, enzyme-responsive peptide functionalized poly(ethylene glycol) (PEG) based hydrogel microparticles were synthesized by an emulsion polymerization. Here, we demonstrate that these microparticles are nontoxic and demonstrated their viability as a drug carrier by studying the encapsulation and release of three types of drugs: a hydrophobic (dexamethasone), a hydrophilic (methylene blue) and a protein (horseradish peroxidase)-based drug. The release of each of these three drugs was studied in the presence of varying concentrations of matrix metalloproteinase (MMP). Each of the three types of drugs were able to be encapsulated in the microparticles, and we further showed that the protein is still functional after release.

Anisotropy in magnetoelectric composites

Anisotropy of piezoelectric and magnetostrictive materials is considered in order to determine the ideal directions and orientation relationships for which the maximum magnetoelectric response may be observed in a composite or heterostructure of these constituent materials. A formalism for the magnetoelectric effect is introduced that takes into account the independent anisotropy of the piezoelectric and magnetostrictive phases and their relative orientation. A maximum magnetoelectric effect is achieved in orientations that have not yet been achieved experimentally, suggesting a need for the development of new routes to synthesize and fabricate designed composite materials with enhanced magnetoelectric response.

Enhanced magnetic resonance contrast of iron oxide nanoparticles embedded in a porous silicon nanoparticle host

In this report, we prepared a porous Si nanoparticle with a pore morphology that facilitates the proximal loading and alignment of magnetite nanoparticles. We characterized the composite materials using superconducting quantum interference device magnetometry, dynamic light scattering, transmission electron microscopy, and MRI. The in vitro cytotoxicity of the composite materials was tested using cell viability assays on human liver cancer cells and rat hepatocytes. An in vivo analysis using a hepatocellular carcinoma (HCC) Sprague Dawley rat model was used to determine the biodistribution properties of the material, while naïve Sprague Dawley rats were used to determine the pharmocokinetic properties of the nanomaterials. The composite material reported here demonstrates an injectable nanomaterial that exploits the dipolar coupling of superparamagnetic nanoparticles trapped within a secondary inorganic matrix to yield significantly enhanced MRI contrast. This preparation successfully avoids agglomeration issues that plague larger ferromagnetic systems. A Fe3O4:pSi composite formulation consisting of 25% by mass Fe3O4 yields an maximal T2* value of 556 mM Fe−1 s−1. No cellular (HepG2 or rat hepatocyte cells) or in vivo (rat) toxicity was observed with the formulation, which degrades and is eliminated after 4–8 h in vivo. The ability to tailor the magnetic properties of such materials may be useful for in vivo imaging, magnetic hyperthermia, or drug-delivery applications.

Nickel-zinc ferrite/permalloy (Ni0.5Zn0.5Fe2O4/Ni-Fe) soft magnetic nanocomposites fabricated by electro-infiltration

Magnetically soft NiZn ferrite (Ni0.5Zn0.5Fe2O4) nanoparticles are embedded within a permalloy (Ni-Fe) matrix via an electro-infiltration process as thin films intended for use as on-chip inductor cores in the MHz frequency regime. A layer of NiZn ferrite nanoparticles is first deposited, and then permalloy is electroplated through the voids to encapsulate the particles and form three-dimensional ferrite/alloy nanocomposites. The composites are estimated to contain 37% ferrite by volume and exhibit a relative permeability of ∼320, a saturation of ∼1.15 T, and an operational bandwidth of 93 MHz. Compared to a permalloy thin film of similar thickness, the nanocomposite exhibits 39% higher electrical resistivity and 50% higher bandwidth.

Electro-infiltration: A method to form nanocomposite soft magnetic cores for integrated magnetic devices

This article introduces a scalable, process-integrable manufacturing method for creating microstructured, nanocomposite soft magnetic cores on planar substrates such as silicon wafers or printed circuit boards. To demonstrate this electro-infiltration process, maghemite (γ-Fe2O3) nanoparticles less than 50 nm are first evaporatively consolidated from suspension into photoresist molds on a silicon substrate, forming dimensionally defined porous microstructures. Next, a high-saturation soft magnetic iron cobalt alloy (Fe–Co) is electroplated up from a conductive layer on the substrate to fill in the void spaces of the consolidated particles. The result is a dense, two-phase nanocomposite, where the maghemite nanoparticles form an inclusion phase in the electroplated metal matrix phase. Improved high-frequency permeability is observed in the 100 MHz–2 GHz range.