A microarray MEMS device for biolistic delivery of vaccine and drug powders.

We report a biolistic technology platform for physical delivery of particle formulations of drugs or vaccines using parallel arrays of microchannels, which generate highly collimated jets of particles with high spatial resolution. Our approach allows for effective delivery of therapeutics sequentially or concurrently (in mixture) at a specified target location or treatment area. We show this new platform enables the delivery of a broad range of particles with various densities and sizes into both in vitro and ex vivo skin models. Penetration depths of ∼1 mm have been achieved following a single ejection of 200 µg high-density gold particles, as well as 13.6 µg low-density polystyrene-based particles into gelatin-based skin simulants at 70 psi inlet gas pressure. Ejection of multiple shots at one treatment site enabled deeper penetration of ∼3 mm in vitro, and delivery of a higher dose of 1 mg gold particles at similar inlet gas pressure. We demonstrate that particle penetration depths can be optimized in vitro by adjusting the inlet pressure of the carrier gas, and dosing is controlled by drug reservoirs that hold precise quantities of the payload, which can be ejected continuously or in pulses. Future investigations include comparison between continuous versus pulsatile payload deliveries. We have successfully delivered plasmid DNA (pDNA)-coated gold particles (1.15 µm diameter) into ex vivo murine and porcine skin at low inlet pressures of ∼30 psi. Integrity analysis of these pDNA-coated gold particles confirmed the preservation of full-length pDNA after each particle preparation and jetting procedures. This technology platform provides distinct capabilities to effectively deliver a broad range of particle formulations into skin with specially designed high-speed microarray ejector nozzles.

Hydrogen peroxide mediated transvaginal drug delivery.

Simple, safe and effective permeability enhancers are crucial for successful non-invasive drug delivery methods. We seek local permeability augmentation mechanisms for integration into passive or active architectures in order to enable novel therapeutic delivery routes of the target drug while minimizing drug formulation challenges. This study explores the efficacy of hydrogen peroxide (HP) as a permeability enhancer for transmucosal delivery of macromolecules. HP at low concentrations (2­8 mM) is an effective permeability enhancer that is locally metabolized and safe. HP improves drug permeation through mucosa by altering tight junctions (TJ) between cells and oxidizing enzymes that function to degrade the foreign species. Results from trans-epithelial electrical resistance measurements and cell viability assay show reversible disassembly of TJ with minimal cell damage demonstrating the feasibility of HP as a safe permeability enhancer for drug delivery. Permeation studies show that HP treatment of cell cultured vaginal mucosa significantly enhances the permeability to insulin by more than an order of magnitude. This work lays foundation for the development of a drug delivery platform that administers drug doses by enhancing the permeability of local epithelial tissue via a separate HP treatment step.

Electrothermally activated microchips for implantable drug delivery and biosensing.

Novel drug delivery and biosensing devices have the potential to increase the efficacy of drug therapy by providing physicians and patients the ability to precisely control key therapy parameters. Such "intelligent" systems can enable control of dose amount and the time, rate, and location of drug delivery. We have developed and demonstrated the operation of an electrothermal mechanism to precisely control the delivery of drugs and exposure of biosensors. These microchip devices contain an array of individually sealed and actuated reservoirs, each capped by a thin metal membrane comprised of either gold or multiple layers of titanium and platinum. The passage of a threshold level of electric current through the membrane causes it to disintegrate, thereby exposing the protected contents (drugs or biosensors) of the reservoir to the surrounding environment. This paper describes the theory and experimental characterization of the electrothermal method and includes in vitro release results for a model compound.

Surface adsorption effects in the inkjet printing of an aqueous polymer solution on a porous oxide ceramic substrate.

The inkjet printing of a polymeric solution into a porous substrate was studied, with the focus on phenomena occurring within the pore space during infiltration. Lines of aqueous polyacrylic acid (PAA) solution were printed onto the surface of porous, high-green-density ceramic powder beds. The PAA is a binder for the ceramic particles, allowing removal of the printed line structure ("primitive") and characterization of the extent of polymer penetration. Large differences in cross section of the retrieved printed structure were observed between ceramic systems and for different specific surface area powders. A mechanism for "filtration" of the polymer by adsorption onto the ceramic particle surfaces during infiltration was proposed. The adsorption of PAA onto Al2O3, SiO2, and TiO2 was characterized via adsorption isotherms, and the trend of primitive cross section with PAA adsorption was consistent with the filtration hypothesis, as was the variation with powder-specific surface area. These results can be generalized to other systems where a solution is inkjet printed onto a porous substrate (e.g., inks on plain paper, porous coated papers, etc.) Utilization of the adsorption effects may allow confinement of the solute molecules (e.g., colorant) to a small region near the substrate surface.

Spreading and infiltration of inkjet-printed polymer solution droplets on a porous substrate.

Simultaneous spreading and infiltration of inkjet-printed droplets has been studied. Small (54- and 63-microm diameter) droplets of an aqueous polymer solution (2.4 vol% polyacrylic acid, PAA, MW 60,000) were deposited on high green density porous ceramic beds, and the wetting-induced spreading and infiltration of the droplets were characterized. The time scales for spreading and infiltration were comparable (approximately milliseconds), resulting in interruption of the spreading prior to completion by infiltration of the liquid into the powder bed, a situation that has received little treatment in the literature. The infiltration time was varied by changing the pore size (via particle size) in the powder bed, and it was confirmed that slower infiltration resulted in greater spreading of the liquid. The spreading and infiltration of the droplet were modeled to examine the coupling between the two processes and allow prediction of the maximum extension of the droplet as a function of the powder bed particle size. The liquid spreading was found to follow r(t)=a(b+t)(n) behavior, and the effect of particle size on infiltration time was used to predict the point at which spreading ceases due to infiltration for various particle sizes.