We examine single step reactive electrospinning of poly(vinyl alcohol) (PVA) and a chemical cross-linking agent, glutaraldehyde (GA), with hydrochloric acid (HCl) as a catalyst to generate water insoluble PVA nanofibers. Such an approach using a conventional setup with no modification enables the fibers to cross-link during the electrospinning process, thereby eliminating the need for post-treatment. Significant changes in the rheological properties occur during in situ cross-linking, which we correlate with electrospinnability. In particular, we associate changes in dynamic rheological properties to changes in fiber morphology for two regions: (1) below the critical concentration to electrospin PVA only and (2) above the critical concentration to electrospin PVA only. In region 1 fiber morphology changes from beaded fibers to uniform fibers to flat fibers, and in region 2 fiber morphology changes from uniform fibers to flat fibers. Electrospinning windows to generate uniform fibers for both regions are determined and can be manipulated by changing the molar ratio of GA to PVA and the volume ratio of HCl to GA. The electrospun fibrous material generated can be rendered insoluble in water, and the uniform fiber morphology can be maintained after soaking in water overnight. The reactive electrospinning process also lowers the critical PVA concentration required for successful electrospinning of the system.

Nanoparticles have shown promise in several biomedical applications, including drug delivery and medical imaging; however, quantitative prediction of nanoparticle formation processes that scale from laboratory to commercial production has been lacking. Flash NanoPrecipitation (FNP) is a scalable technique to form highly loaded, block copolymer protected nanoparticles. Here, the FNP process is shown to strictly obey diffusion-limited aggregation assembly kinetics, and the parameters that control the nanoparticle size and the polymer brush density on the nanoparticle surface are shown. The particle size, ranging from 40 to 200 nm, is insensitive to the molecular weight and chemical composition of the hydrophobic encapsulated material, which is shown to be a consequence of the diffusion-limited growth kinetics. In a simple model derived from these kinetics, a single constant describes the 46 unique nanoparticle formulations produced here. The polymer brush densities on the nanoparticle surface are weakly dependent on the process parameters and are among the densest reported in the literature. Though modest differences in brush densities are observed, there is no measurable difference in the amount of protein adsorbed within this range. This work highlights the material-independent and universal nature of the Flash NanoPrecipitation process, allowing for the rapid translation of formulations to different stabilizing polymers and therapeutic loads.

We present here a systematic investigation to understand why aqueous sodium alginate can only be electrospun into fibers through a blend with another polymer; specifically, polyethylene oxide (PEO). We seek to examine and understand the role of PEO as the “carrier polymer”. The addition of PEO favorably reduces electrical conductivity and surface tension of the alginate solution, aiding in fiber formation. While PEO has the ability to coordinate through its ether group (−COC−) with metal cation like the sodium cation of sodium alginate, we demonstrate in this study using PEO as well as polyvinyl alcohol (PVA) that coordination may have little effect on electrospinnability. More importantly, we show that PEO as carrier polymer provides molecular entanglement that is required for electrospinning. Since the selected carrier polymer provides the necessary entanglement, this carrier polymer must be electrospinnable, entangled and of a high molecular weight (more than 600 kDa for PEO). On the basis of these requirements, we stipulate that the PEO–PEO interaction of the high molecular-weight entangled PEO is key to “carrying” the alginate from solution to fibers during electrospinning. Further, using the resulting understanding of the role of PEO, we were able to increase the alginate concentration by employing a higher molecular-weight PEO: up to 70 wt % alginate using 2000 kDa PEO and, with, the addition of Triton X-100 surfactant, up to 85 wt % alginate, higher than previously reported.

We have developed pH-responsive, multifunctional nanoparticles based on encapsulation of an antioxidant, tannic acid (TA), using Flash NanoPrecipitation, a polymer directed self-assembly method. Formation of insoluble coordination complexes of tannic acid and iron during mixing drives nanoparticle assembly. Tuning the core material to polymer ratio, the size of the nanoparticles can be readily tuned between 50 and 265 nm. The resulting nanoparticle is pH-responsive, i.e. stable at pH 7.4 and soluble under acidic conditions due to the nature of the coordination complex. Further, the coordination complex can be coprecipitated with other hydrophobic materials such as therapeutics or imaging agents. For example, coprecipitation with a hydrophobic fluorescent dye creates fluorescent nanoparticles. In vitro, the nanoparticles have low cytotoxicity show antioxidant activity. Therefore, these particles may facilitate intracellular delivery of antioxidants.