Polystyrene is a synthetic hydrocarbon polymer that is widely adaptive and can be used for a variety of purposes in drug delivery. These methods include polystyrene microspheres, nanoparticles, and solid foams. In the biomedical engineering field, these methods assist researchers in drug delivery, diagnostics, and imaging strategies. A common group of medication that utilizes a combination of polystyrene and sulfonate functional groups are polystyrene sulfonates. This medication is primarily used to treat hyperkalemia, a condition that results from an increased blood potassium level. FDA approved equivalents of polystyrene sulfonates are KIONEX, KALEXATE, and SPS. While these are the only current FDA approved drug that utilizes polystyrene, polystyrene sees a number of applications in other pharmacological contexts with nanoparticles and microspheres.
Drug Delivery Applications
Solid foams Polystyrene integrated solid foams are not commonly used in biomedical applications but have shown promise as a new drug delivery vehicle. The manipulation of the porous foam networks is a fundamental component in solid foam dosing – affecting variables such as dissolution, adsorption, and drug diffusion. Solid foam structures are particularly attractive due to the predictability in drug release profiles through the highly tunable porosity and high surface area of these foams.
The process of creating these structures is typically complex, requiring multiple step processes in order to synthesis a foam of desired properties. However, polystyrene solid foams have been created through simpler methods such as extrusion from a blowing agent or polystyrene bead expansion. While these methods are typically utilized for insulation or similar industry uses, this production method has also seen use in drug delivery applications [5]. Polystyrene solid foams can also be produced through emulsions. An emulsion can be created through the combination of two immiscible liquids. While many methods are used to create emulsion, Canal et al. used a unique method known as phase inversion temperature (PIT). PIT utilizes phase transitions to produce highly concentrated amounts of emulsion quickly. Through changes in temperature, solubility, and low interfacial tension, PIT is able to efficiently promote emulsion. The porosity of these solid foams is able to be fine-tuned, showing promise for osteogenic and therapeutic applications. For example, proposed osteogenic applications include the promotion of bone integration. The study conducted by Canal et al., utilized polystyrene solid foams as a drug delivery method to evaluate the drug release profile of ketoprofen. Researchers have stated that understanding the release profile for various drugs with polystyrene solid foams could significantly improve treatment outcomes for many disease states.
Nanoparticles Nanoparticles have been used in drug delivery for applications such as diagnosis and treatment of diseases, with polymeric nanoparticles gaining significant traction as a carrier of drugs or biomolecules over the last few decades. These structures are extremely small, having a diameter < 100 nm. The high surface to volume ratio allows nanoparticles to display properties that are different than their bulk material in biological systems. These properties have been the sole reason of their use in physiological environments. While the structure of nanoparticles is straightforward, the efficacy of nanoparticles is affected by variables such as size and surface modifications which determines their overall biocompatibility and biological interaction.
Size and Nanoparticle Internalization Polystyrene nanoparticles are the model nanoparticle used for drug delivery applications because they are easy to synthesize in varying sizes. Size is an important factor in cellular uptake rates, which is important for specific pathways such as the endocytic pathway. In a study conducted by Rejman et al., researchers were able to show that polystyrene nanoparticles with diameters of 50 nm and 100 nm were internalized faster than nanoparticles with diameters of 200 nm and 500 nm. Internalization is vital in understanding the impact the designed nanoparticles are having on the target cells. Nanoparticle internalization depends on a couple of key factors such as nanoparticle size, cell type, and time. Nanoparticles of larger size are typically internalized through processes such as phagocytosis or micropinocytosis. Smaller nanoparticles are typically internalized through processes such as macro-pinocytosis, phagocytosis, clathrin-mediated endocytosis, caveolae-mediated endocytosis, and clathrin-and caveolae-independent pathways. The diversity in pathways is one of the greatest challenges with utilizing these nanoparticles since a case-by-case approach is typically required to maximize the entry pathways. To measure nanoparticle internalization, techniques such as fluorescence activated cell sorting/scanning (FACS), inductively coupled plasma (ICP) mass spectroscopy, confocal laser scanning microscopy (CLSM), and imaging flow cytometry (IFC) are utilized, each offering their own advantages and disadvantages.
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