Fabrication and characterization of anisotropic nanofiber scaffolds for advanced drug delivery systems

Abstract

Stimuli-responsive, polymer-based nanostructures with anisotropic compartments are of great interest as advanced materials because they are capable of switching their shape via environmentally-triggered conformational changes, while maintaining discrete compartments. In this study, a new class of stimuli-responsive, anisotropic nanofiber scaffolds with physically and chemically distinct compartments was prepared via electrohydrodynamic cojetting with side-by-side needle geometry. These nanofibers have a thermally responsive, physically-crosslinked compartment, and a chemically-crosslinked compartment at the nanoscale. The thermally responsive compartment is composed of physically crosslinkable poly(N-isopropylacrylamide) poly(NIPAM) copolymers, and poly(NIPAM-co-stearyl acrylate) poly(NIPAM-co-SA), while the thermally-unresponsive compartment is composed of polyethylene glycol dimethacrylates. The two distinct compartments were physically crosslinked by the hydrophobic interaction of the stearyl chains of poly(NIPAM-co-SA) or chemically stabilized via ultraviolet irradiation, and were swollen in physiologically relevant buffers due to their hydrophilic polymer networks. Bicompartmental nanofibers with the physically-crosslinked network of the poly(NIPAM-co-SA) compartment showed a thermally-triggered shape change due to thermally-induced aggregation of poly(NIPAM-co-SA). Furthermore, when bovine serum albumin and dexamethasone phosphate were separately loaded into each compartment, the bicompartmental nanofibers with anisotropic actuation exhibited decoupled, controlled release profiles of both drugs in response to a temperature. A new class of multicompartmental nanofibers could be useful for advanced nanofiber scaffolds with two or more drugs released with different kinetics in response to environmental stimuli.

Thermally-Induced Actuations of Stimuli-Responsive, Bicompartmental Nanofibers for Decoupled Drug Release

“…Furthermore, CLSM images of different BCNFs in Figures 4J–O show that their average diameter in the swollen state changed from 1.94 to 1.35 μm, and that the BCNFs underwent a rapid transition from a linearly extended form to a coil-like one as the temperature increased from 10°C (below their LCST) to 40°C (above their LCST). This resulted from thermally-induced volume decrease of the poly(NIPAM-co-AAh) compartment because of the instantaneous collapse of the poly(NIPAM) copolymers above their LCST and maintenance of the original volume of the PEGDMA copolymer in the swollen state irrespective of temperature, which is in good agreement with a previous study (Jalani et al, 2014). Moreover, the thermal stimulus-triggered transitions of these chemically crosslinked BCNFs, between a fully stretched shape and a coiled one, were completely reversible and stable without any significant aggregation of the nanofibers under aqueous conditions.…”

“…The apparent molar ratio of NIPAM and AAh of poly(NIPAM-co-AAh) and incorporation efficiency of methacrylic groups into allylamine residues of poly(NIPAM-co-AAh) or hydroxyl groups of PEGs were determined by calculating the relative areas under the curves of the corresponding peaks in the 1 H NMR spectrum. In addition, to characterize the thermal responsiveness of the poly(NIPAM-co-AAh) and methacrylated poly(NIPAM-co-AAh), the absorbance of the polymer solution in water at 0.5 and 2.0 w/v % as a function of temperature in the range of 25–50°C was measured at 360 nm using a UV-visible (UV-Vis) spectrometer (Cary-100 Bio, Varian Biotech, Palo Alto, CA, USA) with a Peltier thermostat for temperature control at a heating rate of 1°C /min as previously described (Jalani et al, 2014).…”

“…In addition, chemically controlled bending and reversible shape shifting of multi-compartmental microcylinders induced by different volume transitions were reported for microactuator-based biomedical applications (Saha et al, 2012). Furthermore, anisotropic nanofiber scaffolds composed of physically crosslinked poly(N-isopropylacrylamide-co-stearyl acrylate) (poly(NIPAM- co -SA)) compartments with thermal responsiveness and chemically crosslinked poly(ethylene glycol) (PEG) compartments showed thermally-induced shape changes due to the collapsed poly(NIPAM- co -SA) compartment under aqueous conditions (Jalani et al, 2014). However, there was no clear reversible transition from fully stretched to coiled shapes, potentially due to the physically crosslinked poly(NIPAM- co -SA) networks formed by hydrophobic interactions between SA moieties, limiting their applications such as microactuators, temporally multi-modal drug delivery reservoirs, and shape-morphing hydrogel scaffolds (Browne and Pandit, 2014; Jeon et al, 2017; LöWenberg et al, 2017).…”