Polymeric nanomaterials have the potential to improve upon present chemotherapy delivery methods. They successfully reduce side effects while increasing dosage, increase residence time in the body, offer a sustained and tunable release, and have the ability to deliver multiple drugs in one carrier. However, traditional nanomaterial formulations have not produced highly therapeutic formulations to date due to their passive delivery methods and lack of rapid drug release at their intended site. In this paper, we have focused on a few “smart” technologies that further enhance the benefits of typical nanomaterials. Temperature and pH-responsive drug delivery devices were reviewed as methods for triggering release of encapsulating drugs, while aptamer and ligand conjugation were discussed as methods for targeted and intracellular delivery, with emphases onin vitroandin vivoworks for each method.

Oral administration of monoclonal antibodies (mAbs) may enable the localized treatment of infections or other conditions in the gastrointestinal tract (GI) as well as systemic diseases. As with the development of oral protein biotherapeutics, one of the most challenging tasks in antibody therapies is the loss of biological activity due to physical and chemical instabilities. New families of complexation hydrogels with pH-responsive properties have demonstrated to be excellent transmucosal delivery vehicles. This contribution focuses on the design and evaluation of hydrogel carriers that will minimize the degradation and maximize the in vivo activity of anti-TNF-α, a mAb used for the treatment of inflammatory bowel disease (IBD) in the GI tract and systemically for the treatment of rheumatoid arthritis. P(MAA-g-EG) and P(MAA-co-NVP) hydrogels systems were optimized to achieve adequate swelling behavior, which translated into improved protein loading and release at neutral pH simulating the small intestine conditions. Additionally, these hydrogel systems preserve antibody bioactivity upon release resulting in the systemic circulation of an antibody capable of effectively performing its biological function. The compatibility if these hydrogels for mAb bioactivity preservation and release makes them candidates for use as oral delivery systems for therapeutic antibodies.

Background The “no‐reflow phenomenon” compromises percutaneous coronary intervention outcomes. There is an unmet need for a device that prevents no‐reflow phenomenon. Our goal was to develop a guidewire platform comprising a nondisruptive hydrophilic coating that allows continuous delivery of adenosine throughout a percutaneous coronary intervention. Methods and Results We developed a guidewire with spaced coils to increase surface area for drug loading. Guidewires were plasma treated to attach hydroxyl groups to metal surfaces, and a methoxy–polyethylene glycol–silanol primer layer was covalently linked to hydroxyl groups. Using polyvinyl alcohol, polyvinyl pyrrolidone, and polyvinyl acetate, a drug layer containing jet‐milled adenosine was hydrogen‐bonded to the polyethylene glycol–silanol layer and coated with an outer diffusive barrier layer. Coatings were processed with a freeze/thaw curing method. In vitro release studies were conducted followed by in vivo evaluation in pigs. Coating quality, performance, and stability with sterilization were also evaluated. Antiplatelet properties of the guidewire were also determined. Elution studies with adenosine‐containing guidewires showed curvilinear and complete release of adenosine over 60 minutes. Porcine studies demonstrated that upon insertion into a coronary artery, adenosine‐releasing guidewires induced immediate and robust increases (2.6‐fold) in coronary blood flow velocity, which were sustained for ≈30 minutes without systemic hemodynamic effects or arrhythmias. Adenosine‐loaded wires prevented and reversed coronary vasoconstriction induced by acetylcholine. The wires significantly inhibited platelet aggregation by >80% in vitro. Guidewires passed bench testing for lubricity, adherence, integrity, and tracking. Conclusions Our novel drug‐releasing guidewire platform represents a unique approach to prevent/treat no‐reflow phenomenon during percutaneous coronary intervention.

Crystallite regions within a hydrogel network contribute to its mechanical strength, which is crucial for use in load‐bearing applications. However, high amounts of crystallinity can negatively impact the ability for hydrogels to be injected, an attractive property that could replace the need for highly invasive surgical procedures. The reversibility of crystallinity and its lasting impact on the injectability of poly(vinyl alcohol) and poly(ethylene glycol) hydrogels was evaluated in this paper. The relative percent crystallinity in hydrogels was evaluated after storage and autoclaving in syringes in weekly intervals using X‐ray diffraction. Results indicate that crystallinity increased over time and significantly decreased after autoclaving for all samples, where postautoclaved samples contained comparable crystallinity percentages to freshly made gels (p > 0.05). Injectability was evaluated using calculated viscosity. Aged samples were able to be injected after autoclaving, yet there was no determination established between viscosity and storage times based on the data. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020, 137, 48706.

Receptor-mediated endocytosis (RME) has been extensively studied as a method for augmenting the transport of therapeutic devices across monolayers. These devices range from simple ligand-therapeutic conjugates to complex ligand-nanocarrier systems. However, characterizing the uptake of these carriers typically relies on their comparisons to the native therapeutic, which provides no understanding of ligand or cellular performance. To better understand the potential of the RME pathway, a model for monolayer transport was designed based on the endocytosis cycle of transferrin, a ligand often used in RME drug-delivery devices. This model established the correlation between apical receptor concentration and transport capability. Experimental studies confirmed this relationship, demonstrating an upper transport limit independent of the applied dose. This contrasts with the dose-proportional pathways native therapeutics rely on for transport. Thus, the direct comparison of these two transport mechanisms can produce misleading results that change with arbitrarily chosen doses. Furthermore, transport potential was hindered by repeated use of the RME-cycle. Future studies should base the success of this technology not on the performance of the therapeutic itself, but on the capabilities of the cell. Using receptor-binding studies, we were able to demonstrate how these capabilities can be predicted and potentially adopted for high-throughput screening methods.