Nanoparticle multilayers: surface modification of photosensitive drug microparticles for increased stability and in vitro bioavailability.

The results of this study report the novel use of electrostatic layer-by-layer nanoassembly of biocompatible nanoparticulate TiO2 multilayers to coat irregular nifedipine (NF) microcrystals to increase the photostability of the drug when exposed to simulated sunlight and to increase the dissolution rate and possibly the bioavailability of the drug after oral administration. The photostability of NF microcrystals (35 microm) coated with multiple bilayers of positively charged PDDA and negatively charged nanosized TiO2 particles (20-25 nm) was measured when exposed to an illuminance of 12 W/m2 corresponding to a light dose of 30 k lux or 25 W/m2 corresponding to light dose of 60 k lux. The dissolution rate of nifedipine from the coated microcrystals was measured in simulated gastric fluid containing 0.05% w/v polysorbate 80. Coating with one TiO2 layer increased the shelf life of nifedipine by 30 hours independent of the intensity of the light exposure. With an increase in the number of TiO2 layers; the photostability of the drug was enhanced even more. A TiO2 monolayer decreased the contact angle by 20 degrees for water and 33 degrees for the dissolution medium as compared with uncoated NF surfaces. This increase in wettability due to a decrease in contact angle increased the dissolution rate of nifedipine microcrystals coated with 1 PDDA/TiO2 bilayer 13-fold after 10 minutes, 5-fold after 1 hour, and 2-fold after 12 hours when compared to uncoated microcrystals. It is assumed that TiO2 increased the photostability because the nanoparticulate multilayers acts as a potential filter protecting the drug from damaging light rays reaching the drug crystals. The dissolution rate was increased because the hydrophilic TiO2 nanoparticles increased the aqueous wettability of the drug crystals thereby preventing aggregation in the dissolution medium. This ensured that the maximum drug surface area was exposed to the dissolution medium.

Layer-by-layer enzyme/polyelectrolyte films as a functional protective barrier in oxidizing media.

The influence of a catalase (Cat) layer located at different depths in the layer-by-layer hemoglobin/polystyrene sulfonate films with an (Hb/PSS)(20)(-)(x)/(Cat/PSS)/(Hb/PSS)(x) (x = 0-20) architecture on kinetics of hemoglobin degradation under treatment with hydrogen peroxide solutions of different concentrations and features of H(2)O(2) decay in surrounding solutions has been studied. While assembled on the top of the multilayers, the catalase layer shows the highest activity in hydrogen peroxide decomposition. Hemoglobin in such films retains its nativity for a longer period of time. The effect of catalase layers is compared with that of protamine, horseradish peroxidase, and inactivated catalase. Positioning an active layer with catalytic properties as an outer layer is the best protection strategy for layer-by-layer assembled films in aggressive media.

Stem cell attachment to layer-by-layer assembled TiO2 nanoparticle thin films.

Surface topography is one of the most important factors influencing the attachment and spreading of cells. In the present study, layer-by-layer assembled titanium dioxide (TiO2) nanoparticle thin films were chosen for attachment, proliferation and spreading studies on mouse mesenchymal stem cells (MSC). Increasing surface roughness was observed with increasing number of layer-by-layer assembled TiO2 thin films. Four layer TiO2 thin film showed higher number of attached cells than a one layer thin film and control surfaces. MSCs experienced no cytotoxic effects after culture on the TiO2 coated substrates as observed from the cytotoxicity tests. Cell spreading, visualized with scanning electron microscopy, showed a faster rate of spreading on a rougher surface. Cells on a four-layer substrate, at 12 h showed complete spreading, where as most of the cells on a control surface and a one-layer surface, at 24 h, retained a rounded morphology. In conclusion, TiO2 nanoparticle thin films were successfully assembled in alternation with polyelectrolytes and in-vitro studies with MSC showed an increase in the attachment and faster spreading of cells on rougher surfaces.

Layer-by-Layer assembly of TiO2 nanoparticles for stable hydrophilic biocompatible coatings.

Stable, super-hydrophilic (water contact angle approximately equal to 0 degrees) titanium dioxide nanoparticle thin films have been obtained on substrates with different initial wettability such as glass, poly(methyl methacrylate) and poly(dimethyl siloxane) using layer-by-layer nano-assembly method. Titanium dioxide nanoparticles were alternated with poly(styrene sulfonate) to form films of thickness ranging from 11 nm to 220 nm. The hydrophilicity of these thin films increases with increasing number of deposited PSS/TiO2 bilayers. It was found that 2, 5 and 20 layers were needed to form super-hydrophilic TiO2 coating on glass, PMMA and PDMS respectively. Oxygen plasma treatment of substrate surfaces enhanced the formation of homogeneous TiO2 films and accelerated the formation of hydrophilic layers. Super-hydrophilicity has been shown to be unique to PSS/TiO2 films as compared with other polyelectrolyte/nanoparticle layers, and UV irradiation may restore hydrophilicity even after months of storing of the samples. Biocompatibility of TiO2 nanoparticle films has been demonstrated by the successful cell culture of human dermal fibroblast.