Student Award for Outstanding Research Winner in the Undergraduate Category for the 2017 Society for Biomaterials Annual Meeting and Exposition, April 5-8, 2017, Minneapolis, Minnesota: Development and characterization of stimuli-responsive hydrogel microcarriers for oral protein delivery.

A family of pH-responsive terpolymers composed of methacrylic acid (MAA), N-vinyl pyrrolidone (NVP), and poly(ethylene glycol) monomethylether monomethacrylate (PEGMMA) have been developed and evaluated for their pH-responsive swelling behavior, protein-loading capabilities, and cytocompatibility. These terpolymer hydrogels, designated as P((MAA-co-NVP)-g-EG), were synthesized with varying PEG chain lengths and monomer feed ratios. The incorporation of MAA into the terpolymer structure was quantified with potentiometric titration. Equilibrium and dynamic swelling studies confirmed the pH-responsive behavior of the hydrogel, with the system remaining collapsed/complexed in acidic pH conditions and swollen/decomplexed in neutral pH conditions. The ability of the hydrogels to partition protein into the swollen network was assessed for two model proteins of varying molecular weight: insulin and porcine growth hormone. Finally, the cytocompatibility of the hydrogels in the presence of two model intestinal cell lines was investigated and confirmed minimal cytotoxicity at and below 2.5 mg/mL. The developed P((MAA-co-NVP)-g-EG) hydrogels exhibit unique properties that could potentially be utilized for drug delivery and separation applications. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1243-1251, 2017.

Development of a P((MAA-co-NVP)-g-EG) Hydrogel Platform for Oral Protein Delivery: Effects of Hydrogel Composition on Environmental Response and Protein Partitioning.

Hydrogels based upon terpolymers of methacrylic acid, N-vinyl pyrrolidone, and poly(ethylene glycol) are developed and characterized for their ability to respond to changes in environmental pH and to partition protein therapeutics of varying molecular weights and isoelectric points. P((MAA-co-NVP)-g-EG) hydrogels are synthesized with PEG-based cross-linking agents of varying length and incorporation densities. The composition is confirmed using FT-IR spectroscopy and shows peak shifts indicating hydrogen bonding. Scanning electron microscopy reveals microparticles with an irregular, planar morphology. The pH-responsive behavior of the hydrogels is confirmed under equilibrium and dynamic conditions, with the hydrogel collapsed at acidic pH and swollen at neutral pH. The ability of the hydrogels to partition model protein therapeutics at varying pH and ionic strength is evaluated using three model proteins: insulin, porcine growth hormone, and ovalbumin. Finally, the microparticles are evaluated for adverse interactions with two model intestinal cell lines and show minimal cytotoxicity at concentrations below 5 mg mL-1 .

A Closer Look at the Impact of Molecular Imprinting on Adsorption Capacity and Selectivity for Protein Templates.

Molecularly imprinted polymers (MIPs) are often investigated as lower cost, more environmentally robust alternatives to natural recognitive biomolecules, such as antibodies. When synthesized on the surface of nanomaterial supports, MIPs are capable of quick and effective binding of macromolecular templates when compared to traditional bulk-imprinted polymers. We have developed a method for imprinting proteins on biodegradable nanoparticle supports and have used these materials to investigate the impact of molecular imprinting on adsorption capacity and selectivity for lysozyme, the template protein. The imprinting process increased the adsorption capacity of the polymer for the template, lysozyme, with the MIPs being able to bind up to 83.5% of their dry weight as compared to 55.7% for nonimprinted polymers (NIPs). In noncompetitive binding experiments, where proteins were independently incubated with MIPs, the difference between adsorption capacity for lysozyme and proteins with much lower isoelectric points (pI < 8.0) was statistically significant. However, there was no statistical difference between adsorption capacity for lysozyme and other high-isoelectric point proteins, suggesting that MIPs are semiselective for this class of proteins. In competitive binding experiments, both MIPs and NIPs preferentially bound lysozyme over other high-isoelectric point proteins. This result demonstrated that imprinting alone could not account for the observed selectivity for lysozyme. Analysis of the solvent accessible surface area of lysozyme and its high-isoelectric point competitors revealed why lysozyme is an exceptional binder to the polymer system used in this work, with or without imprinting.

Versatile Route to Colloidal Stability and Surface Functionalization of Hydrophobic Nanomaterials.

We introduce a general method for the stabilization and surface functionalization of hydrophobic nanoparticles using an amphiphilic copolymer, poly(maleic anhydride-alt-1-octadecene)-poly(ethylene glycol) methacrylate (PMAO-PEGMA). Coating nanoparticles with PMAO-PEGMA results in colloidally stable nanoparticles decorated with reactive carboxylic acid and methacrylate functionalities, providing a versatile platform for chemical reactions. The versatility and ease of surface functionalization is demonstrated by varying both the core material and the chemistry used. Specifically, the carboxylic acid functionalities are used to conjugate wheat germ agglutinin to conducting polymer nanoparticles via carbodiimide-mediated coupling, and the methacrylate groups are used to link cysteamine to the surface of poly(ε-caprolactone) nanoparticles via thiol-ene click chemistry and to link temperature-responsive polymer shells to the surface of gold nanoparticles via free radical polymerization.

Stimulus-responsive hydrogels: Theory, modern advances, and applications.

Over the past century, hydrogels have emerged as effective materials for an immense variety of applications. The unique network structure of hydrogels enables very high levels of hydrophilicity and biocompatibility, while at the same time exhibiting the soft physical properties associated with living tissue, making them ideal biomaterials. Stimulus-responsive hydrogels have been especially impactful, allowing for unprecedented levels of control over material properties in response to external cues. This enhanced control has enabled groundbreaking advances in healthcare, allowing for more effective treatment of a vast array of diseases and improved approaches for tissue engineering and wound healing. In this extensive review, we identify and discuss the multitude of response modalities that have been developed, including temperature, pH, chemical, light, electro, and shear-sensitive hydrogels. We discuss the theoretical analysis of hydrogel properties and the mechanisms used to create these responses, highlighting both the pioneering and most recent work in all of these fields. Finally, we review the many current and proposed applications of these hydrogels in medicine and industry.

A review of current nanoparticle and targeting moieties for the delivery of cancer therapeutics.

The tumor microenvironment provides unique challenges for the delivery of chemotherapeutic agents in doses that are effective while ensuring minimal systemic toxicity. The primary limitation of current therapeutics is a lack of specificity in delivery, as they target healthy and cancerous cells alike. The development of nanoscale carriers capable of delivering cancer therapies has the potential to overcome both systemic and tumor barriers and provide specific, targeted delivery. This review seeks to provide an overview of available nanoscale drug carriers by exploring the wide variety of developed nanostructures and the most commonly used moieties for targeted delivery. Additionally, the use of nanoscale carriers will be motivated by examining tumor physiology and the specific barriers present within both the tumor microenvironment and systemic delivery.