Anodic Voltage Dependence of Ti-6Al-4V Substrates and Hydroxyapatite Coating.

Ti-6Al-4V alloys were anodized in a solution containing 0.15 M HF and 2 M H3PO4 for 30 min under different voltages and then coated with hydroxyapatite (HA) by hydrothermal-electrochemical deposition. The effects of anodizing voltage on the morphology and bioactivity of the HA coating and on the bonding strength between the HA coating and the anodized substrates were investigated. Results indicated that highly ordered amorphous TiO2 nanotube arrays formed on the Ti-6Al-4V surface after anodic oxidation. The pore size of the nanotube increased up to approximately 100 nm with increasing anodic voltage until 25 V. The nanotube was damaged at anodic voltages above 25 V. The crystal structure of TiO2 changed from amorphous to anatase when the anodized substrates were heated at 450 °C for 3 h. The contact angle between the Ti-6Al-4V surfaces and the simulated body fluid evidently decreased after anodic oxidation. The roughness increased with increasing anodic voltage, and Ra reached about 0.56 µm under 25 V. The HA coating exhibited layered growth. The deposition of rod-like HA crystals as well as the crystallinity of the HA coating initially increased and then decreased with the further increase of the anodic volatage. The degree of crystallinity reached the maximum of approximately 73% at 25 V. The bonding strength between the coating and the anodized substrates increased and then slightly decreased with increasing voltage. The bonding strength was about 20.0 MPa when titanium substrate was anodized under 25 V. The results of simulated body fluid immersing experiments suggest that the HA coating exhibits promising bioactivity.

Electrospun Hydrophilic Janus Nanocomposites for the Rapid Onset of Therapeutic Action of Helicid.

The oral delivery of active ingredients for the fast onset of therapeutic effects is a well-known method in patients. In this study, a new kind of hydrophilic Janus structural nanocomposite was designed for the rapid dissolution and transmembrane permeation of helicid, an herbal medicine with poor water solubility. A side-by-side electrospinning process characterized by an eccentric spinneret was developed to fabricate the Janus nanocomposites. The morphology, inner structure, incorporated components and their physical states, hydrophilicity, and functional performances of the Janus nanocomposites were investigated. The experimental results demonstrated that an unspinnable fluid (polyvinylpyrrolidone K10-sodium dodecyl sulfate) could be simultaneously treated with an electrospinnable fluid (polyvinylpyrrolidone K90-helicid) to create Janus structural nanocomposites. The prepared Janus nanofibers exhibited linear morphology and notable side-by-side inner structure with all the incorporated components present in an amorphous state. Both the control of monolithic nanocomposites and the Janus composites can provide more than 10-fold the transmembrane rates of crude helicid particles. Compared with monolithic nanocomposites, the Janus nanocomposites exhibited improved hydrophilicity and can further promote the dissolution and transmembrane permeation of helicid for a potentially faster onset of therapeutic actions. The generation mechanisms and functional performance of Janus nanocomposites were suggested. The preparation protocols reported here can provide a useful approach for designing and developing new functional nanocomposites in the form of Janus structures. Meanwhile, the medicated hydrophilic Janus nanocomposites represent a newly developed kind of nano drug delivery system for the fast onset of therapeutic action of orally administered water-insoluble drugs.

Electrospun hypromellose-based hydrophilic composites for rapid dissolution of poorly water-soluble drug.

Hypromellose (HPMC)-based hydrophilic composites (HCs) used for rapid dissolution of ferulic acid (FA) were investigated. Electrospun and casting HCs were prepared from a solution containing HPMC, FA, and polyethylene glycol. Ethanol was used as sheath fluid during coaxial processes, and the effects of its flow rates on the Taylor cone and straight fluid jet were investigated. The morphology, component state, hydrophilicity, and drug dissolution rate of the HCs were characterized. Results demonstrated that all HCs were amorphous materials, and their components were compatible. However, the dissolution rate of electrospun HCs was 10 times faster than that of casting HCs. The smaller the diameters of electrospun HCs were, the better their performances were. The mechanism of electrospun HCs was suggested. By utilizing modified coaxial electrospinning and combinations of drug carriers, new types of HPMC-based HCs can provide an alternative approach for the effective delivery of poorly water-soluble drugs.

Electrospun pH-sensitive core-shell polymer nanocomposites fabricated using a tri-axial process.

A modified tri-axial electrospinning process was developed for the generation of a new type of pH-sensitive polymer/lipid nanocomposite. The systems produced are able to promote both dissolution and permeation of a model poorly water-soluble drug. First, we show that it is possible to run a tri-axial process with only one of the three fluids being electrospinnable. Using an electrospinnable middle fluid of Eudragit S100 (ES100) with pure ethanol as the outer solvent and an unspinnable lecithin-diclofenac sodium (PL-DS) core solution, nanofibers with linear morphology and clear core/shell structures can be fabricated continuously and smoothly. X-ray diffraction proved that these nanofibers are structural nanocomposites with the drug present in an amorphous state. In vitro dissolution tests demonstrated that the formulations could preclude release in acidic conditions, and that the drug was released from the fibers in two successive steps at neutral pH. The first step is the dissolution of the shell ES100 and the conversion of the core PL-DS into sub-micron sized particles. This frees some DS into solution, and later the remaining DS is gradually released from the PL-DS particles through diffusion. Ex vivo permeation results showed that the composite nanofibers give a more than twofold uplift in the amount of DS passing through the colonic membrane as compared to pure DS; 74% of the transmitted drug was in the form of PL-DS particles. The new tri-axial electrospinning process developed in this work provides a platform to fabricate structural nanomaterials, and the core-shell polymer-PL nanocomposites we have produced have significant potential applications for oral colon-targeted drug delivery. STATEMENT OF SIGNIFICANCE: A modified tri-axial electrospinning is demonstrated to create a new type of core-shell pH-sensitive polymer/lipid nanocomposites, in which an electrospinnable middle fluid is exploited to support the un-spinnable outer and inner fluids. The structural nanocomposites are able to provide a colon-targeted sustained release and an enhanced permeation performance of diclofenac sodium. The developed tri-axial process can provide a platform for fabricating new structural nanomaterials with high quality. The strategy of a combined usage of polymeric excipients and phospholipid in a core-shell format should provide new possibilities of developing novel drug delivery systems for efficacious oral administration of poorly-water soluble drugs.