Adsorption Dynamics of Uremic Toxins to Novel Modified Magnetic Nanoparticles.

Kidney dysfunction leads to the retention of metabolites in the blood compartment, some of which reach toxic levels. Uremic toxins are associated with the progression of kidney disease and other symptoms of kidney failure (i.e., nausea, itchiness, and hypertension). Toxin removal ameliorates symptoms and reduces further organ damage, but membrane-based methods are inadequate for this purpose. Engineered adsorbents may facilitate enhanced removal of retained toxins, especially those bound strongly by proteins. Poly 2-(methacryloyloxy)ethyl phosphorylcholine-co-ß-cyclodextrin (p(MPC-co-PMßCD)) coated magnetic nanoparticles are synthesized, characterized for their physicochemical properties (Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), thermogravimetric analysis(TGA), gel permeation chromatography (GPC), and transmission electron microscope (TEM), and evaluated toxin adsorption from a complex solution for the first time to quantify the effects of film chemistry and incubation time on the adsorbed toxinome (the collection of toxins). Uremic toxins are bound by even "low-fouling" polymer films themselves; providing further insight into how small molecule interactions with "low-fouling" films may affect protein-surface interactions. These results suggest a dynamic interaction between toxins and surfaces that is not driven by solution concentration alone. This knowledge will help advance the design of novel adsorbent films for clearing uremic toxins.

Hemocompatibility of ß-Cyclodextrin-Modified (Methacryloyloxy)ethyl Phosphorylcholine Coated Magnetic Nanoparticles.

Adsorbing toxins from the blood to augment membrane-based hemodialysis is an active area of research. Films composed of ß-cyclodextrin-co-(methacryloyloxy)ethyl phosphorylcholine (p(PMßCD-co-MPC)) with various monomer ratios were formed on magnetic nanoparticles and characterized. Surface chemistry effects on protein denaturation were evaluated and indicated that unmodified magnetic nanoparticles greatly perturbed the structure of proteins compared to coated particles. Plasma clotting assays were conducted to investigate the stability of plasma in the presence of particles, where a 2:2 monomer ratio yielded the best results for a given total surface area of particles. Total protein adsorption results revealed that modified surfaces exhibited reduced protein adsorption compared to bare particles, and pure MPC showed the lowest adsorption. Immunoblot results showed that fibrinogen, α1-antitrypsin, vitronectin, prekallikrein, antithrombin, albumin, and C3 correlated with film composition. Hemocompatibility testing with whole blood illustrated that the 1:3 ratio of CD to MPC had a negative impact on platelets, as evidenced by the increased activation, reduced response to an agonist, and reduced platelet count. Other formulations had statistically significant effects on platelet activation, but no formulation yielded apparent adverse effects on hemostasis. For the first time, p(PMßCD-co-MPC)-coated MNP were synthesized and their general hemocompatibility assessed.

UV-B induced fibrillization of crystallin protein mixtures.

Environmental factors, mainly oxidative stress and exposure to sunlight, induce the oxidation, cross-linking, cleavage, and deamination of crystallin proteins, resulting in their aggregation and, ultimately, cataract formation. Various denaturants have been used to initiate the aggregation of crystallin proteins in vitro. All of these regimens, however, are obviously far from replicating conditions that exist in vivo that lead to cataract formation. In fact, it is our supposition that only UV-B radiation may mimic the observed in vivo cause of crystallin alteration leading to cataract formation. This means of inducing cataract formation may provide the most appropriate in vitro platform for in-depth study of the fundamental cataractous fibril properties and allow for testing of possible treatment strategies. Herein, we showed that cataractous fibrils can be formed using UV-B radiation from α:ß:γ crystallin protein mixtures. Characterization of the properties of formed aggregates confirmed the development of amyloid-like fibrils, which are in cross-ß-pattern and possibly in anti-parallel ß-sheet arrangement. Furthermore, we were also able to confirm that the presence of the molecular chaperone, α-crystallin, was able to inhibit fibril formation, as observed for 'naturally' occurring fibrils. Finally, the time-dependent fibrillation profile was found to be similar to the gradual formation of age-related nuclear cataracts. This data provided evidence for the initiation of fibril formation from physiologically relevant crystallin mixtures using UV-B radiation, and that the formed fibrils had several traits similar to that expected from cataracts developing in vivo.

Nanotechnology-Based Approaches for Ophthalmology Applications: Therapeutic and Diagnostic Strategies.

PURPOSE: The purpose of this article was to review recent advances in applications of nanotechnology in ophthalmology. DESIGN: Literature review. METHODS: Research articles about nanotechnology-based treatments for particular eye diseases and diagnostic technologies were searched through Web of Science, and the most recent advances were reported. RESULTS: Nanotechnology enabled to improve drug and gene delivery systems, medicine solubility and short half-life in biological systems, controlled release, targeted delivery, bioavailability, diffusion limitations, and biocompatibility so far. These promising achievements are the assurance of next-generation treatment technologies. As well as treatment, nanofabrications systems such as microelectromechanical manufacturing systems removed the limitations of nanodevice generations and led the development of diagnostic tools such as intraocular pressure monitors and biosensors. CONCLUSIONS: The pursuit of personalized medicine approaches for combating ocular diseases may be possible only through the development of nanotechnology platforms that include molecular-level engineering. Nanoparticle engineering is a common thread; herein, we attempt to show unmodified nanoparticles as well as interesting and representative biomimetic strategies can be used for specific diseases. Finally, through combining microelectromechanical and nanoelectromechanical manufacturing system strategies, interesting manufacturing and sensor development can be accomplished for early detection and, in some cases, treatment of ocular diseases.