In this investigation, novel biodegradable physically crosslinked hydrogel micro-particles were developed and evaluated in vitro as potential carriers for sustained pulmonary drug delivery. To facilitate sustained release in the lungs, aerosols must first navigate past efficient aerodynamic filtering to penetrate to the deep lung (requires small particle size) where they must then avoid rapid macrophage clearance (enhanced by large particle size). The strategy suggested in this study to solve this problem is to deliver drug-loaded hydrogel microparticles with aerodynamic characteristics allowing them to be respirable when dry but attain large swollen sizes once deposited on moist lung surfaces to reduce macrophage uptake rates. The microparticles are based on PEG graft copolymerized onto chitosan in combination with Pluronic® F-108 and were prepared via cryomilling. The synthesized polymers used in preparation of the microparticles were characterized using FTIR, EA, 2D-XRD, and differential scanning calorimetry (DSC). The microparticles size, morphology, moisture content, and biodegradation rates were investigated. Swelling studies and in vitro drug release profiles were determined. An aerosolization study was conducted and macrophage uptake rates were evaluated against controls. The microparticles showed a respirable fraction of approximately 15% when prepared as dry powders. Enzymatic degradation of microparticles started within the first hour and about 7–41% weights were remaining after 240 h. Microparticles showed sustained release up to 10 and 20 days in the presence and absence of lysozyme, respectively. Preliminary macrophage interaction studies indicate that the developed hydrogel microparticles significantly delayed phagocytosis and may have the potential for sustained drug delivery to the lung.

The mucus barrier is well established as a formidable barrier to exogenous substances and forms the first line of defense for mucosal surfaces. Drugs and particle systems are known to be significantly hindered via a variety of interactions with mucus and some efforts have been reported that can mitigate these interactions. We investigated topically applied particulate systems (nano and micro) for their potential to interact with mucus and influence on the diffusion of model drugs across the mucus barrier. Functionalized polystyrene nanoparticles and microparticles and diesel particulate matter were topically applied to established in vitro mucus models. Particle treated mucus was then assessed, compared to controls, for drug permeation rates. The average permeation rate of drugs increased 2-fold following the application of particles to mucus compared to permeation of the same drug through mucus alone. In some cases permeation enhancement of small model drugs was over 5 times that of controls. Assessment of particle physicochemical properties also indicated that significant interactions occurred between mucus and the particles as determined by zeta potential changes and size changes. Collectively this work supports the hypothesis that topically applied particles interact with the mucus barrier causing disruption of this barrier allowing for increased drug permeation. These findings have implications for improved drug delivery and enhanced environmental exposure to exogenous substances.

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The effect of power level on the microwave heating characteristics of a variety of reagent-grade chemicals and minerals has been determined in a Bureau of Mines study.Heating rates of the powdered samples are presented for incident power ranging from 500 to 2,000 W at 2.45 GHz.The apparatus consisted of a WR 975 waveguide-applicator mounted to WR 284 waveguide sections and connected to a 3-kW power source.Tests were conducted in an alumina crucible enclosed in a fused-quartz beaker that was fitted with a TeflonI lid to allow for a controlled inert atmosphere and thermocouple insertion.In general, heating rates increased as input power increased. Exceptions to this were some very high-lossy (microwave receptive) and very low-lossy materials that showed negligible changes with increased power. Microwave data collected should provide insight as to possible chemical and mineral processing applications as well as to assist in predictions of processing parameters.

The purpose of this study is to investigate the potential of magnetic nanoparticles for enhancing drug delivery using a low oscillating magnetic field (OMF) strength. We investigated the ability of magnetic nanoparticles to cause disruption of a viscous biopolymer barrier to drug delivery and the potential to induce triggered release of drug conjugated to the surfaces of these particles. Various magnetic nanoparticles were screened for thermal response under a 295-kHz OMF with an amplitude of 3.1 kA/m. Based on thermal activity of particles screened, we selected the nanoparticles that displayed desired characteristics for evaluation in a simplified model of an extracellular barrier to drug delivery, using lambda DNA/HindIII. Results indicate that nanoparticles could be used to induce DNA breakage to enhance local diffusion of drugs, despite low temperatures of heating. Additional studies showed increased diffusion of quantum dots in this model by single-particle tracking methods. Bimane was conjugated to the surface of magnetic nanoparticles. Fluorescence and transmission electron microscope images of the conjugated nanoparticles indicated little change in the overall appearance of the nanoparticles. A release study showed greater drug release using OMF, while maintaining low bulk heating of the samples (T = 30 degrees C). This study indicates that lower magnetic field strengths may be successfully utilized for drug delivery applications as a method for drug delivery transport enhancement and drug release switches.