Viral nanoparticles have been utilized as a platform for vaccine development and are a versatile system for the display of antigenic epitopes for a variety of disease states. However, the induction of a clinically relevant immune response often requires multiple injections over an extended period of time, limiting patient compliance. Polymeric systems to deliver proteinaceous materials have been extensively researched to provide sustained release, which would limit administration to a single dose. Melt-processing is an emerging manufacturing method that has been utilized to create polymeric materials laden with proteins as an alternative to typical solvent-based production methods. Melt-processing is advantageous because it is continuous, solvent-free, and 100% of the therapeutic protein is encapsulated. In this study, we utilized melt-encapsulation to fabricate viral nanoparticle laden polymeric materials that effectively deliver intact particles and generate carrier specific antibodies in vivo. The effects of initial processing and postprocessing on particle integrity and aggregation were studied to develop processing windows for scale-up and the creation of more complex materials. The dispersion of particles within the PLGA matrix was studied, and the effect of additives and loading level on the release profile was determined. Overall, melt-encapsulation was found to be an effective method to produce composite materials that can deliver viral nanoparticles over an extended period and elicit an immune response comparable to typical administration schedules.
A molecularly imprinted polymer (MIP) fi lm for dopamine (DP) sensing is fabricated from cathodically electrodeposited p -aminostyrene (PAS) on electrode surfaces in a surface plasmon resonance (SPR) spectroscopy setup. The monomer is more commonly used in monolithic MIP free-radical bulk polymerizations. The fi lm growth and rebinding of DP are monitored by electrochemical-SPR (EC-SPR) spectroscopy. UV-Vis, IR spectroscopy, XPS, AFM, and electrochemistry methods are used to characterize the fi lm. High selectivity against analogous analytes and up to picomolar detection of DP is demonstrated. The reusability of the sensor is also established. Theoretical modeling studies with AM1 calculations predict H-bonding in a stable prepolymerization complex in solution prior to MIP fi lm formation. intermolecular forces of association. Covalent [ 8 ] and noncovalent interactions [ 9 ] are the primary classifi cation attributed to the association mechanism in MIP. In the case of non-covalent binding, the interactions between monomer or polymer and template molecule include Van der Waals forces, dipole-dipole, and hydrogen (H)-bonding. The choice of crosslinking monomers with proper functionality plays an important role in MIP. Much effort has been directed toward the optimal choice of monomer and crosslinker combinations for the effective imprinting of the template molecule, enabling both covalent and non-covalent associations. [ 10 ] While the monolith approach is commonly utilized in making MIPs for separations or chromatography applications, the preparation of thin MIP fi lms is essential for effective and direct coupling of the sensing element fi lm onto the transducer surface in a sensor device. The bulk MIP approach such as in the case of monolith usually faces several shortcomings such as slow binding kinetics, poor selectivity, low capacity, or less template loading, and require substantial amounts of template for imprinting. In situ monitoring of the release and rebinding of the template molecule in bulk MIP is relatively more diffi cult since the imprinted
Drug delivery strategies generally use inert materials, such as high molecular weight polymers, to encapsulate and control the release rate of therapeutic drugs. Diffusion governs release and depends on the ease of permeation of the polymer alongside the device thickness. Yet in applications such as osteoarthritis, the physiological constraints and limited intra-articular joint space prevent the use of large, solid drug delivery implants. Other investigators have explored the use of micro- and nanoparticle drug delivery systems. However, the small size of the systems limits the total drug that may be encapsulated and its short diffusion distance causes rapid release. Ordinarily, the extremely low diffusivity of a polymer fluid would make this an unsuitable delivery system. Our technology takes advantage of specific molecular interactions between drug and polymer, which can control the rate of release beyond diffusion. With this "affinity-based drug delivery", we have shown that delivery rates from solid polymer can be prolonged from hours and days, to weeks and months. In this paper, we demonstrate that this affinity-based mechanism also applies to low diffusivity fluid-phase polymers. They show release rates that are substantially slower than chemically similar polymers incapable of forming those inclusion complexes. The similarity of this study's liquid polymers to the viscoelastic fluids used in current clinical practice makes it an ample delivery system for osteoarthritic application. We confirmed the capacity of anti-inflammatory delivery of corticosteroids: hydrocortisone, triamcinolone, and dexamethasone; from both solid implants and polymer fluids. Further, we demonstrated that viscoelastic properties are widely tunable, and within the range of native synovial fluid. Lastly, we determined these polymer fluids have no impact on the differentiation of mesenchymal stem cells to cartilage and are not cytotoxic to a common cell line.
In this paper, covalently linked graphene oxide–poly(ethylene glycol) methyl ether methacrylate–reversible addition‐fragmentation chain transfer (GO–PEGMEMA–RAFT) and physically mixed GO–PEGMEMA hydrogel nanocomposites are synthesized. Spectroscopic and imaging techniques such as UV–vis, Fourier transform infrared, Raman spectroscopy, and transmission electron microscopy show that the PEGMEMA is successfully grafted on GO sheets. The rheology of the nanocomposites is studied by small angle oscillatory shear, which shows a competition between reinforcement and lubrication behavior of GO. In the case where lubrication effect dominates reinforcement, the covalently linked GO–PEGMEMA–RAFT has higher G′ compared to the physically mixed GO‐PEGMEMA. Hence, in the covalently linked system, the grafted polymer chains appear to minimize the lubrication effect.
Layered annular structures produced with layer multiplication coextrusion, utilizing both a standard in‐line “spider” die, and a custom annular die, are compared in structures up to 129 layers. One multilayered system, of a Dow LDPE 5004I was utilized in generating experimental results to validate the custom die design performance. It was found that the custom design demonstrates successful extrusion of high layer number annular structures with substantial benefits over the standard spider die. Moreover, a design method incorporating angular rotation was implemented within the custom die to eliminate weld lines and attain concentric layer structures to further enhance commercial viability and mechanical integrity. Results indicate angular rotation may be utilized to generate idealized annular products with concentric layer structures. Additionally, exploration of flow through the annular die land was conducted with ANSYS Polyflow in under several conditions of angular rotation. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 137, 48683.
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