@article{conner_mcandrew_menegatti_velev_2022, title={An accelerated antibody aggregation test based on time sequenced dynamic light scattering}, volume={653}, ISSN={["1873-4359"]}, DOI={10.1016/j.colsurfa.2022.129833}, abstractNote={A rapid method for determination of the colloidal stability of protein molecules in solution is reported as an efficient tool for evaluating the stability of antibody formulations. Using human polyclonal immunoglobulin G (IgG) as a model protein and dynamic light scattering (DLS) as a technique to determine the size of particles in solution, the rate of aggregation is investigated at different temperatures and antibody concentrations. To reduce the observation period while increasing precision, a new approach to DLS analysis is developed that comprises: (i) a distribution analysis of high-resolution data, and fitting for multiple particle sizes present in a solution, (ii) a temperature ramp to an intermediate temperature followed by a stress test at constant temperature over several hours, and (iii) 3-D plotting to reveal the time-dependent evolution of the particle size distribution at the selected temperature. The resulting 3-D plots enable robust identification of the onset of aggregation with different dispersion conditions. This method enables rapid evaluation of the effects of parameters such as temperature and concentration on the stability of antibody solutions.}, journal={COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS}, author={Conner, Cathryn G. and McAndrew, James and Menegatti, Stefano and Velev, Orlin D.}, year={2022}, month={Nov} } @article{stine_harper_conner_velev_harper_2021, title={In Vivo Toxicity Assessment of Chitosan-Coated Lignin Nanoparticles in Embryonic Zebrafish (Danio rerio)}, volume={11}, ISSN={["2079-4991"]}, url={https://www.mdpi.com/2079-4991/11/1/111}, DOI={10.3390/nano11010111}, abstractNote={Lignin is the second most abundant biopolymer on Earth after cellulose. Since lignin breaks down in the environment naturally, lignin nanoparticles may serve as biodegradable carriers of biocidal actives with minimal environmental footprint compared to conventional antimicrobial formulations. Here, a lignin nanoparticle (LNP) coated with chitosan was engineered. Previous studies show both lignin and chitosan to exhibit antimicrobial properties. Another study showed that adding a chitosan coating can improve the adsorption of LNPs to biological samples by electrostatic adherence to oppositely charged surfaces. Our objective was to determine if these engineered particles would elicit toxicological responses, utilizing embryonic zebrafish toxicity assays. Zebrafish were exposed to nanoparticles with an intact chorionic membrane and with the chorion enzymatically removed to allow for direct contact of particles with the developing embryo. Both mortality and sublethal endpoints were analyzed. Mortality rates were significantly greater for chitosan-coated LNPs (Ch-LNPs) compared to plain LNPs and control groups. Significant sublethal endpoints were observed in groups exposed to Ch-LNPs with chorionic membranes intact. Our study indicated that engineered Ch-LNP formulations at high concentrations were more toxic than plain LNPs. Further study is warranted to fully understand the mechanisms of Ch-LNP toxicity.}, number={1}, journal={NANOMATERIALS}, author={Stine, Jared S. and Harper, Bryan J. and Conner, Cathryn G. and Velev, Orlin D. and Harper, Stacey L.}, year={2021}, month={Jan} } @article{conner_veleva_paunov_stoyanov_velev_2020, title={Scalable Formation of Concentrated Monodisperse Lignin Nanoparticles by Recirculation-Enhanced Flash Nanoprecipitation}, volume={37}, ISSN={["1521-4117"]}, DOI={10.1002/ppsc.202000122}, abstractNote={AbstractA highly controllable and scalable process for fabrication of large amounts of concentrated lignin nanoparticles (LNPs) is reported. These lignin core nanoparticles are formed through flash nanoprecipitation, however, scaling up of the fabrication process requires fundamental understanding of their operational formation mechanism and surface properties. It is shown how a semicontinuous synthesis system with a recirculation loop makes it possible to produce flash precipitated lignin nanoparticles in large amounts for practical applications. The roles of the process parameters, including flow rates and lignin concentration, are investigated and analyzed. The results indicate that the LNPs are formed by a process of continuous burst nucleation at the point of mixing without diffusive growth, which yields nanoparticles of highly uniform size following a modified LaMer nucleation and growth mechanism. This mechanism makes possible facile process control and scaleā€up. Effective control of the resulting nanoparticle size is achieved through the initial concentration of lignin in the injected solution. The impressive capability to produce suspensions of any predesigned multimodal distribution is demonstrated. The resulting nanofabrication technique can produce large volumes of concentrated LNP suspensions of high stability and tightly controlled size distributions for biological or agricultural applications.}, number={7}, journal={PARTICLE & PARTICLE SYSTEMS CHARACTERIZATION}, author={Conner, Cathryn G. and Veleva, Anka N. and Paunov, Vesselin N. and Stoyanov, Simeon D. and Velev, Orlin D.}, year={2020}, month={Jul} } @article{nix_harper_conner_richter_velev_harper_2018, title={Toxicological Assessment of a Lignin Core Nanoparticle Doped with Silver as an Alternative to Conventional Silver Core Nanoparticles}, volume={7}, ISSN={["2079-6382"]}, url={http://www.mdpi.com/2079-6382/7/2/40}, DOI={10.3390/antibiotics7020040}, abstractNote={Elevated levels of silver in the environment are anticipated with an increase in silver nanoparticle (AgNP) production and use in consumer products. To potentially reduce the burden of silver ion release from conventional solid core AgNPs, a lignin-core particle doped with silver ions and surface-stabilized with a polycationic electrolyte layer was engineered. Our objective was to determine whether any of the formulation components elicit toxicological responses using embryonic zebrafish. Ionic silver and free surface stabilizer were the most toxic constituents, although when associated separately or together with the lignin core particles, the toxicity of the formulations decreased significantly. The overall toxicity of lignin formulations containing silver was similar to other studies on a silver mass basis, and led to a significantly higher prevalence of uninflated swim bladder and yolk sac edema. Comparative analysis of dialyzed samples which had leached their loosely bound Ag+, showed a significant increase in mortality immediately after dialysis, in addition to eliciting significant increases in types of sublethal responses relative to the freshly prepared non-dialyzed samples. ICP-OES/MS analysis indicated that silver ion release from the particle into solution was continuous, and the rate of release differed when the surface stabilizer was not present. Overall, our study indicates that the lignin core is an effective alternative to conventional solid core AgNPs for potentially reducing the burden of silver released into the environment from a variety of consumer products.}, number={2}, journal={ANTIBIOTICS-BASEL}, author={Nix, Cassandra E. and Harper, Bryan J. and Conner, Cathryn G. and Richter, Alexander P. and Velev, Orlin D. and Harper, Stacey L.}, year={2018}, month={Jun} }