Publications

2010
S. J. Yoon, Mallidi, S., Tam, J. M., Tam, J. O., Murthy, A., Joshi, P., Johnston, K. P., Sokolov, K. V., and Emelianov, S. Y., “Biodegradable plasmonic nanoclusters as contrast agent for photoacoustic imaging,” in Photons Plus Ultrasound: Imaging and Sensing 2010, vol. 7564, A. A. Oraevsky and Wang, L. V., Ed. 2010. Publisher's VersionAbstract
Metallic nanoparticles have been widely used in a variety of imaging and therapeutic applications due to their unique optical properties in the visible and near-infrared (NIR) regions - for example, various plasmonic nanoparticles are used for molecular photoacoustic imaging and photothermal therapy. However, there are concerns that these agents may not be safe under physiological conditions, because these nanoparticles are not biodegradable, could accumulate and, therefore, could be toxic long-term. We investigate the feasibility of using biodegradable gold nanoclusters as a contrast agent for highly sensitive photoacoustic imaging. The size of these biodegradable nanoclusters, consisting of sub-5 nm primary gold particles and a biodegradable polymer binder, is less than 100 nm. Due to plasmon coupling, these nanoclusters are characterized by a broad extinction spectrum that extends to the near infrared (NIR) spectral range. Photoacoustic imaging of tissue models containing inclusions with different concentrations of nanoparticles was performed using a tunable pulsed laser system. The results indicate that the biodegradable nanoclusters, comprised of small gold nanoparticles, can be used as contrast agents in photoacoustic imaging.
2009
L. L. Ma, Feldman, M. D., Tam, J. M., Paranjape, A. S., Cheruku, K. K., Larson, T. A., Tam, J. O., Ingram, D. R., Paramita, V., Villard, J. W., Jenkins, J. T., Wang, T., Clarke, G. D., Asmis, R., Sokolov, K., Chandrasekar, B., Milner, T. E., and Johnston, K. P., “Small Multifunctional Nanoclusters (Nanoroses) for Targeted Cellular Imaging and Therapy,” Acs Nano, vol. 3, pp. 2686-2696, 2009. Publisher's VersionAbstract
The ability of 20-50 nm nanoparticles to target and modulate the biology of specific types of cells will enable major advancements in cellular imaging and therapy in cancer and atherosclerosis. A key challenge is to load an extremely high degree of targeting, imaging, and therapeutic functionality into small, yet stable particles. Herein we report similar to 30 nm stable uniformly sized near-infrared (NIR) active, superparamagnetic nanoclusters formed by kinetically controlled self-assembly of gold-coated iron oxide nanoparticles. The controlled assembly of nanocomposite particles into clusters with small primary particle spacings produces collective responses of the electrons that shift the absorbance into the NIR region. The nanoclusters of similar to 70 iron oxide primary particles with thin gold coatings display intense NIR (700-850 nm) absorbance with a cross section of similar to 10(-14) m(2). Because of the thin gold shells with an average thickness of only 2 nm, the r(2) spin-spin magnetic relaxivity is 219 mM(-1) s(-1), an order of magnitude larger than observed for typical iron oxide particles with thicker gold shells. Despite only 12% by weight polymeric stabilizer, the particle size and NIR absorbance change very little in delonized water over 8 months. High uptake of the nanoclusters by macrophages is facilitated by the dextran coating, producing intense NIR contrast in dark field and hyperspectral microscopy, both in cell culture and an in vivo rabbit model of atherosclerosis. Small nanoclusters with optical, magnetic, and therapeutic functionality, designed by assembly of nanciparticle building blocks, offer broad opportunities for targeted cellular imaging, therapy, and combined imaging and therapy.
G. Gupta, Slanac, D. A., Kumar, P., Wiggins-Camacho, J. D., Wang, X. Q., Swinnea, S., More, K. L., Dai, S., Stevenson, K. J., and Johnston, K. P., “Highly Stable and Active Pt-Cu Oxygen Reduction Electrocatalysts Based on Mesoporous Graphitic Carbon Supports,” Chemistry of Materials, vol. 21, pp. 4515-4526, 2009. Publisher's VersionAbstract
The activity of oxygen reduction catalysts for fuel cells often decreases markedly (30-70%) during potential cycling tests designed to accelerate catalyst degradation. Herein we achieved essentially no loss in electrochemical surface area and catalyst activity during potential cycling from 0.5 to 1.2 V for presynthesized Pt-Cu nanoparticles of controlled composition that were infused into highly graphitic disordered mesoporous carbons (DMC). The high stability is favored by the strong metal-support interactions and low tendency for carbon oxidation, which mitigates the mechanisms of degradation. Electrochemical dealloying transforms the composition from Pt20Cu80 to Pt85Cu15 with a strained Pt-rich shell, which exhibits an enhanced ORR activity of 0.46 A/mg(Pt), > 4 fold that of pure Pt catalysts. The high uniformity in particle size and composition both before and after dealloying, as a consequence of the presynthesis/infusion technique, is beneficial For elucidating the mechanism of catalyst activity and, ultimately, for designing more active catalysts.
M. E. Matteucci, Paguio, J. C., Miller, M. A., Williams, R. O., and Johnston, K. P., “Highly Supersaturated Solutions from Dissolution of Amorphous Itraconazole Microparticles at pH 6.8,” Molecular Pharmaceutics, vol. 6, pp. 375-385, 2009. Publisher's VersionAbstract
Dry powders from aqueous dispersions, formed by antisolvent precipitation, dissolved to form solutions with supersaturation values up to 12 in 10 min at pH 6.8 with sodium dodecyl sulfate micelles. Itraconazole/hydroxypropylmethylcellulose (HPMC) aqueous particle dispersions were salt flocculated and filtered to produce medium surface area (2-5 m(2)/g) particles or lyophilized to produce high surface area (13-36 m(2)/g). Over 4 h, the decay in supersaturation was much slower for the medium surface area versus high surface area particles, since the smaller excess surface area of undissolved particles led to slower nucleation and growth from solution. A slow decay in supersaturation was also achieved by initially dissolving part of the drug at pH 1.2, and then shifting the pH to 6.8 thereby reducing the excess surface area of undissolved particles in the pH 6.8 media. This pH shift mimics the transition from stomach to intestines. The ability to generate and sustain high supersaturation at pH 6.8 by minimizing undissolved excess surface area may be expected to be beneficial for raising bioavailability by gastrointestinal delivery.
K. A. Overhoff, Johnston, K. P., Tam, J., Engstrom, J., and Williams, R. O., “Use of thin film freezing to enable drug delivery: a review,” Journal of Drug Delivery Science and Technology, vol. 19, pp. 89-98, 2009. Publisher's VersionAbstract
Particle engineering may be used to improve the physicochemical properties of many new chemical entities to enhance the bioavailability. In "bottom up" technologies, particles may be formed by precipitation to control physicochemical properties including the particle size, surface characteristics, morphology, and crystallinity. This review, provides an overview of various precipitation technologies used in pharmaceutical development. but highlights rapid freezing technologies, with emphasis on thin film freezing (TFF). In thin film freezing, the particle morphology may be controlled by manipulating the fluid dynamics and heat tran, fer properties upon spreading and freezing of liquid droplets on solid surfaces. Finally, in vitro and in vivo studies utilizing TFF are, reviewed to emphasize the potential benefits of this technology in improving drug performance.
K. P. Johnston and da Rocha, S. R. P., “Colloids in supercritical fluids over the last 20 years and future directions,” Journal of Supercritical Fluids, vol. 47, pp. 523-530, 2009. Publisher's VersionAbstract
In this work, the history of colloids in supercritical fluids in the last two decades and future directions in several promising areas are discussed. The primary focus of this article is on microemulsions and emulsions, although new developments are described involving protein colloids, electrostatic stabilization of inorganic particles and the use of CO(2) as an antisolvent for separation of metal colloids. The focus on the CO(2)-water interface is related to the fact that, historically, the studies of colloids in supercritical fluids began with microemulsions and emulsions, and then evolved to polymer latexes and inorganic dispersions. Moreover, many of the same types of stabilizers have been used for the various types of colloids. (C) 2008 Published by Elsevier B.V.
J. M. Jung, Ganapathy, H. S., Yuvaraj, H., Johnston, K. P., and Lim, K. T., “Removal of HF/CO2 post-etch residues from pattern wafers using water-in-carbon dioxide microemulsions,” Microelectronic Engineering, vol. 86, pp. 165-170, 2009. Publisher's VersionAbstract
We have investigated different methods for removing the HF/CO2 post-etch residues from blanket and patterned wafers of borophosphosilicate glass. The use of co-solvents, rinsing the residues with DI water followed by CO2-based drying process, and the use of water-in-CO2 (W/C) microemulsions were explored as possible methods to remove the etch residues. It was found that the addition of co-solvents were ineffective for quantitative removal of residues, whereas rinsing the etch residues with DI water followed by the surfactant-aided scCO(2) drying was found to be effective. To eliminate the pure water rinsing step, W/C microemulsions formed with different surfactants were directly treated with residues. While ionic surfactants such as ammonium carboxylate perfluoropolyether and sodium salt of bis (1H,1H,2H,2H-trideca-fluoro-octyl)-2-sulfosuccinate did not produce stable microemulsions in the presence of HF, due to protonation effect, the reverse micelles formed with an amphiphilic block copolymeric surfactant, poly(ethylene oxide-b-perfluorooctylmethacrylate), was found to be highly efficient as clean and residue-free images were observed by microscopic analysis. (c) 2008 Elsevier B.V. All rights reserved
L. L. Ma, Feldman, M. D., Tam, J. O., Tam, J. M., Rigdon, D. C., Villard, J. W., Sokolov, K., Milner, T. E., and Johnston, K. P., “BIOT 115-Small nanoclusters (nanoroses) by assembly of nanoparticle building blocks with high near infrared absorbance for cellular imaging and therapy,” Abstracts of Papers of the American Chemical Society, vol. 238, 2009. Publisher's VersionAbstract
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J. M. Tam, Tam, J. O., Murthy, A. K., Ingram, D. R., Travis, K. A., Sokolov, K., and Johnston, K. P., “BIOT 149-Gold clusters for near infrared imaging and therapy,” Abstracts of Papers of the American Chemical Society, vol. 238, 2009. Publisher's VersionAbstract
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M. A. Miller, Engstrom, J. D., Irvin, A. L., Ludher, B. S., and Johnston, K. P., “BIOT 156-Low viscosity, highly concentrated suspensions of protein particles suitable for subcutaneous delivery,” Abstracts of Papers of the American Chemical Society, vol. 238, 2009. Publisher's VersionAbstract
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R. A. May, Patel, M. N., Johnston, K. P., and Stevenson, K. J., “Flow-Based Multiadsorbate Ellipsometric Porosimetry for the Characterization of Mesoporous Pt-TiO2 and Au-TiO2 Nanocomposites,” Langmuir, vol. 25, pp. 4498-4509, 2009. Publisher's VersionAbstract
Au and Pt nanoparticle distributions within hierarchically ordered mesoporous TiO2 were explored using a combination of techniques including ellipsometric porosimetry (EP) and X-ray photoelectron spectroscopy (XPS). EP studies were used to examine adsorbate-TiO2 interactions and the influence of adsorbate polarity upon adsorption isotherms for mesoporous TiO2 films with and without Pt and Au nanoparticles. In particular, methods are described for modeling EP data to estimate the surface area and porosity of mesoporous TiO2 films and for estimating the pore size distribution (PSD) directly from the ellipsometry parameters Psi and Delta when fitting parameters alone are unable to extract reliable optical constants from the ellipsometry data. This approach reveals that mesoporous TiO2 films of similar to 200 nm thickness and similar to 10 nm pore diameter can be loaded with 1.7 nm diameter Pt and 3.9 nm diameter Au nanoparticles up to 26 and 21 wt %, respectively. The BET surface area of a representative mesoporous TiO2 sample using toluene as the adsorbate was found to be 44 m(2)/g with a mean pore diameter of 8.8 nm. EP and XPS depth profiling experiments indicate that 1.7 nm diameter Pt nanoparticles are well dispersed through the mesoporous TiO2 film, while 3.9 nm diameter Au nanoparticles are concentrated at the top of the film, blocking a significant portion of the available TiO2 pore volume. UV irradiation of the TiO2 films indicates that adsorbate-TiO2 interactions and surface wetting effects can play a critical role in the resulting isotherm and in evaluation of PSD.
M. Qu, Mallidi, S., Mehrmohammadi, M., Ma, L. L., Johnston, K. P., Sokolov, K., Emelianov, S., and Ieee,Combined Photoacoustic and Magneto-Acoustic Imaging,” in 2009 Annual International Conference of the Ieee Engineering in Medicine and Biology Society, Vols 1-20, 2009, pp. 4763-4766. Publisher's VersionAbstract
Ultrasound is a widely used modality with excellent spatial resolution, low cost, portability, reliability and safety. In clinical practice and in the biomedical field, molecular ultrasound-based imaging techniques are desired to visualize tissue pathologies, such as cancer. In this paper, we present an advanced imaging technique - combined photoacoustic and magneto-acoustic imaging - capable of visualizing the anatomical, functional and biomechanical properties of tissues or organs. The experiments to test the combined imaging technique were performed using dual, nanoparticle-based contrast agents that exhibit the desired optical and magnetic properties. The results of our study demonstrate the feasibility of the combined photoacoustic and magneto-acoustic imaging that takes the advantages of each imaging techniques and provides high sensitivity, reliable contrast and good penetrating depth. Therefore, the developed imaging technique can be used in wide range of biomedical and clinical application.
X. X. Chen, Matteucci, M. E., Lo, C. Y., Johnston, K. P., and Williams, R. O., “Flocculation of Polymer Stabilized Nanocrystal Suspensions to Produce Redispersible Powders,” Drug Development and Industrial Pharmacy, vol. 35, pp. 283-296, 2009. Publisher's VersionAbstract
Aqueous suspensions of crystalline naproxen nanoparticles, formed by antisolvent precipitation, were flocculated with sodium sulfate, filtered, and dried to form redispersible powders for oral delivery. The particles were stabilized with polyvinylpyrrolidone (PVP K-15) and/or poly(ethylene oxide-b-propylene oxide-b-ethylene oxide) (poloxamer 407). The yield of the drug in the powder was typically 92-99%, and the drug loading was reproducible to within 1-2%. The filtration process increased the drug loading by up to 61% relative to the initial value, as unbound surfactant was removed with the filtrate. Upon redispersion of the dried powder, the average particle size measured by light scattering was comparable to the original value in the aqueous suspension prior to flocculation, and consistent with primary particle sizes observed by scanning electron microscopy (SEM). For 300-nm particles, up to 95% of the drug dissolved in 2 min. The dissolution rate was correlated linearly with the specific surface area calculated from the average particle diameter after redispersion. The redispersion of dried powders was examined as a function of the salt concentration used for flocculation and the surfactant composition and concentration. Flocculation followed by filtration and drying is an efficient and highly reproducible process for the rapid recovery of drug nanoparticles to produce wettable powders with high drug loading and rapid dissolution.
2008
W. Yang, Tam, J., Miller, D. A., Zhou, J., McConville, J. T., Johnston, K. P., and Williams, R. O., “High bioavailability from nebulized itraconazole nanoparticle dispersions with biocompatible stabilizers,” International Journal of Pharmaceutics, vol. 361, pp. 177-188, 2008. Publisher's VersionAbstract
A nebulized dispersion of amorphous, high surface area, nanostructured aggregates of itraconazole (ITZ): mannitol: lecithin (1:0.5:0.2, w/w) yielded improved bioavailability in mice. The ultra-rapid freezing (URF) technique used to produce the nanoparticles was found to molecularly disperse the ITZ with the excipients as a solid solution. Upon addition to water, ITZ formed a colloidal dispersion suitable for nebulization, which demonstrated optimal aerodynamic properties for deep lung delivery and high lung and systemic levels when dosed to mice. The ITZ nanoparticles produced supersaturation levels 27 times the crystalline solubility upon dissolution in simulated lung fluid. A dissolution/permeation model indicated that the absorption of 3 mu m ITZ particles is limited by the dissolution rate (BCS Class II behavior), while absorption is permeation-limited for more rapidly dissolving 230 nm particles. The predicted absorption half-life for 230 turn amorphous ITZ particles was only 15 min, as a result of the small particle size and high supersaturation, in general agreement with the in vivo results. Thus, bioavailability may be enhanced, by decreasing the particle size to accelerate dissolution and increasing permeation with (I) an amorphous morphology to raise the drug solubility, and (2) permeability enhancers. (C) 2008 Elsevier B.V. All rights reserved.
K. M. Do, Yuvaraj, H., Woo, M. H., Kim, H. G., Jeong, E. D., Johnston, K. P., and Lim, K. T., “Synthesis of polystyrene/SiO(2) composite microparticles by dispersion polymerization in supercritical fluid,” Colloid and Polymer Science, vol. 286, pp. 1343-1348, 2008. Publisher's VersionAbstract
A novel synthetic route to prepare polystyrene/SiO(2) composite microparticles in supercritical carbon dioxide (scCO(2)) is presented. Silica particles with the size of 130 nm which were surface-modified with 3-(trimethoxysilyl) propyl methacrylate were used as seeds in the dispersion polymerization of styrene in the presence of a polymeric stabilizer, poly(1,1-dihydroheptafluorobutyl methacrylate-co-diisopropylaminoethyl methacrylate) to produce dry composite particles. The transmission electron microscopy analysis revealed that the composite microspheres contained several silica particles.
M. N. Patel, Williams, R. D., May, R. A., Uchida, H., Stevenson, K. J., and Johnston, K. P., “Electrophoretic Deposition of Au Nanocrystals inside Perpendicular Mesochannels of TiO2,” Chemistry of Materials, vol. 20, pp. 6029-6040, 2008. Publisher's VersionAbstract
Au nanocrystals stabilized by dodecanethiol were deposited into 100-150 run thick TiO2, films with evenly spaced perpendicular nanopillars and mesochannels oil the order of 10 nm supported oil conducting ITO/glass electrodes. Electrophoretic deposition was used to enhance nanocrystal deposition within the mesoporous TiO2 film. X-ray photoelectron spectroscopy (XPS), scanning electron microscopy with energy dispersive X-ray (EDX), UV-vis spectroscopy, variable-angle spectroscopic ellipsometry (VASE). and scanning Surface potential microscopy (SSPM) were used to characterize the resulting Au nanocrystal/ TiO, composites. Au nanocrystal loadings reached 21 wt % and were not kinetically limited at 10 min, relative to depositions performed for 20 h. Both VASE Measurements of the anisotropy of the imaginary refractive index, k, and X-ray photoelectron spectroscopy (XPS) depth profiling Studies indicate that Au nanocrystals are dispersed within the vertically aligned mesopores and distributed throughout the film. The mean penetration depth of a single nanocrystal penetrating inside the film is described with I model in terms of the electric field and a local deposition rate constant, which is influenced by ligand binding and architecture oil the nanocrystal surface.
M. E. Matteucci, Paguio, J. C., Miller, M. A., Williams, R. O., and Johnston, K. P., “Flocculated amorphous nanoparticles for highly supersaturated solutions,” Pharmaceutical Research, vol. 25, pp. 2477-2487, 2008. Publisher's VersionAbstract
Purpose. To recover polymer-stabilized amorphous nanoparticles from aqueous dispersions efficiently by salt flocculation and to show that the particles redisperse and dissolve rapidly to produce highly supersaturated solutions. Methods. Nanoparticle dispersions of itraconazole stabilized by nonionic polymers were formed by antisolvent precipitation and immediately flocculated with sodium sulfate, filtered and dried. The size after redispersion in water, crystallinity, and morphology were compared with those for particles produced by spray drying and rapid freezing. Results. Particle drug loading increased to similar to 90% after salt flocculation and removal of excess polymer with the filtrate. The formation of the flocs at constant particle volume fraction led to low fractal dimensions (open flocs), which facilitated redispersion in water to the original primary particle size of similar to 300 nm. Amorphous particles, which were preserved throughout the flocculation-filtration-drying process, dissolved to supersaturation levels of up to 14 in pH 6.8 media. In contrast, both spray dried and rapidly frozen nanoparticle dispersions crystallized and did not produce submicron particle dispersions upon addition to water, nor high supersaturation values. Conclusions. Salt flocculation produces large yields of high surface area amorphous nanoparticle powders that de-aggregate and dissolve rapidly upon redispersion in pH 6.8 media, for supersaturation levels up to 14.
J. M. Tam, McConville, J. T., Williams, R. O., and Johnston, K. P., “Amorphous Cyclosporin Nanodispersions for Enhanced Pulmonary Deposition and Dissolution,” Journal of Pharmaceutical Sciences, vol. 97, pp. 4915-4933, 2008. Publisher's VersionAbstract
Aqueous colloidal dispersions of amorphous cyclosporin A (CsA) nanoparticles, intended for pulmonary delivery, were formed by antisolvent precipitation and stabilized with 10% polysorbate 80. Dissolution of the dispersion of CsA nanoparticles produced supersaturation values 18 times the aqueous equilibrium solubility. Nebulization of the dispersion to mice produced therapeutic lung levels and systemic concentrations below toxic limits. The sizes of the aerosolized aqueous droplets are optimal for deep lung deposition, whereas the amorphous drug nanoparticles facilitate rapid dissolution. A dissolution/permeation model was developed to characterize the effects of particle size, solubility, and drug dose on the absorption half-lives of poorly water soluble drugs in the alveolar epithelium. For crystalline 3 mu m particles with a solubility of 1 mu g/mL, the half-life for absorption was estimated to be 500 min. The half-life may be reduced to less than I min by increasing the solubility by a factor of 100 with an amorphous form as well as by decreasing the particle size 10-fold. The in vitro and in vivo data, as well as the dissolution/permeation model, indicate that nebulization of amorphous nanoparticle suspensions has the potential to enhance lung epithelial absorption markedly for poorly water soluble drugs, relative to respiratory delivery of crystalline, micron-sized particles. (C) 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:4915-4933, 2008
J. D. Engstrom, Lai, E. S., Ludher, B. S., Chen, B., Milner, T. E., Williams, R. O., Kitto, G. B., and Johnston, K. P., “Formation of stable submicron protein particles by thin film freezing,” Pharmaceutical Research, vol. 25, pp. 1334-1346, 2008. Publisher's VersionAbstract
Purpose. Highly stable, submicron lactate dehydrogenase (LDH) and lysozyme particles may be produced by thin film freezing (TFF) of aqueous solutions followed by lyophilization. Methods. The LDH activity was determined by measuring the decrease in absorbance of NADH over time for the reaction of pyruvate to lactate. For lysozyme the particle morphology was determined by scanning electron microscopy (SEM) and compared with the specific surface area (BET) and the particle size, as measured by laser light scattering, Results. Protein particles with an average diameter of 300 nm and 100% enzyme activity upon reconstitution (for LDH) were formed by TFF. Droplets of protein solutions, 3.6 mm in diameter, spread upon impact with 223 and 133 K metal surfaces to form cylindrical disks with thicknesses of 200-300 mu m. Calculated cooling rates of the disks of 10(2) K/s were confirmed experimentally with infrared measurements. Conclusions. The cooling rates of 10(2) K/s, intermediate to those in lyophilization (1 K/min) and spray freeze-drying (SFD) (10(6) K/s), were sufficiently fast to produce sub-micron protein particles with surface areas of 31-73 m(2)/g, an order of magnitude higher than in lyophilization. In addition, the low surface area/volume ratio (32-45 cm(-1)) of the gas-liquid interface led to minimal protein adsorption and denaturation relative to SFD.
K. A. Overhoff, McConville, J. T., Yang, W., Johnston, K. P., Peters, J. I., and Williams, R. O., “Effect of stabilizer on the maximum degree and extent of supersaturation and oral absorption of tacrolimus made by ultra-rapid freezing,” Pharmaceutical Research, vol. 25, pp. 167-175, 2008. Publisher's VersionAbstract
Purpose. Solid dispersions containing various stabilizers and tacrolimus (TAC) prepared by an Ultra-rapid Freezing (URF) process were investigated to determine the effect on their ability to form supersaturated solutions in aqueous media and on enhancing transport across biological membranes. Materials and Methods. The stabilizers included poly(vinyl alcohol; PVA), poloxamer 407 (P407), and sodium dodecyl sulfate (SDS). In vivo absorption enhancement in rats was also investigated. Dissolution studies were conducted at supersaturated conditions in both acidic media for 24 h and at delayed release (enteric) conditions to simulate intestinal transit. Results. The rank order of C/Ceq(max) in the dissolution studies at acidic conditions was URF-P407 > URF-SDS > Prograf((R)) (PRO)> URF-PVA:P407. For C/Ceq(max) under enteric conditions, the order was URF-SDS > PRO > URF-PVA:P407 > URF-P407, and for the extent of supersaturation (AUC) in acidic and pH shift conditions it was URF-SDS > PRO > URF-PVA:P407 > URF-P407. The pharmacokinetic data suggests URF-P407 had the greatest absorption having higher C(max) with a 1.5-fold increase in AUC compared to PRO. All URF compositions had a shorter T(max) compared to PRO. Conclusions. The nanostructured powders containing various stabilizing polymers formed by the URF process offer enhanced supersaturation characteristics leading to increased oral absorption of TAC.

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