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.

Electrospun Contrast Agent-Loaded Fibers for Colon-Targeted MRI

Magnetic resonance imaging is a diagnostic tool used for detecting abnormal organs and tissues, often using Gd(III) complexes as contrast-enhancing agents. In this work, core–shell polymer fibers have been prepared using coaxial electrospinning, with the intent of delivering gadolinium (III) diethylenetriaminepentaacetate hydrate (Gd(DTPA)) selectively to the colon. The fibers comprise a poly(ethylene oxide) (PEO) core loaded with Gd(DTPA), and a Eudragit S100 shell. They are homogeneous, with distinct core–shell phases. The components in the fibers are dispersed in an amorphous fashion. The proton relaxivities of Gd(DTPA) are preserved after electrospinning. To permit easy visualization of the release of the active ingredient from the fibers, analogous materials are prepared loaded with the dye rhodamine B. Very little release is seen in a pH 1.0 buffer, while sustained release is seen at pH 7.4. The fibers thus have the potential to selectively deliver Gd(DTPA) to the colon. Mucoadhesion studies reveal there are strong adhesive forces between porcine colon mucosa and PEO from the core, and the dye-loaded fibers can be successfully used to image the porcine colon wall. The electrospun core–shell fibers prepared in this work can thus be developed as advanced functional materials for effective imaging of colonic abnormalities.

Theranostic Fibers for Simultaneous Imaging and Drug Delivery

New methods for creating theranostic systems with simultaneous encapsulation of therapeutic, diagnostic, and targeting agents are much sought after. This work reports for the first time the use of coaxial electrospinning to prepare such systems in the form of core–shell fibers. Eudragit S100 was used to form the shell of the fibers, while the core comprised poly(ethylene oxide) loaded with the magnetic resonance contrast agent Gd(DTPA) (Gd(III) diethylenetriaminepentaacetate hydrate) and indomethacin as a model therapeutic agent. The fibers had linear cylindrical morphologies with clear core–shell structures, as demonstrated by electron microscopy. X-ray diffraction and differential scanning calorimetry proved that both indomethacin and Gd(DTPA) were present in the fibers in the amorphous physical form. This is thought to be a result of intermolecular interactions between the different components, the presence of which was suggested by infrared spectroscopy. In vitro dissolution tests indicated that the fibers could provide targeted release of the active ingredients through a combined mechanism of erosion and diffusion. The proton relaxivities for Gd(DTPA) released from the fibers into tris buffer increased (r1 = 4.79–9.75 s–1 mM–1; r2 = 7.98–14.22 s–1 mM–1) compared with fresh Gd(DTPA) (r1 = 4.13 s–1 mM–1 and r2 = 4.40 s–1 mM–1), which proved that electrospinning has not diminished the contrast properties of the complex. The new systems reported herein thus offer a new platform for delivering therapeutic and imaging agents simultaneously to the colon.