Supercritical carbon dioxide (SC-CO₂) can serve as solvent, anti-solvent and solute, among others, in the field of drug delivery applications, e.g., for the formulation of polymeric nanocarriers in combination with different drug molecules. With its tunable properties above critical pressure and temperature, SC-CO₂ offers control of the particle size, the particle morphology, and their drug loading. Moreover, the SC-CO₂-based techniques overcome the limitations of conventional formulation techniques e.g., post purification steps. One of the widely used polymers for drug delivery systems with excellent mechanical (T_g, crystallinity) and chemical properties (controlled drug release, biodegradability) is poly (lactic acid) (PLA), which is used either as a homopolymer or as a copolymer, such as poly(lactic-co-glycolic) acid (PLGA). Over the last 30 years, extensive research has been conducted to exploit SC-CO₂-based processes for the formulation of PLA carriers. This review provides an overview of these research studies, including a brief description of the SC-CO₂ processes that are widely exploited for the production of PLA and PLGA-based drug-loaded particles. Finally, recent work shows progress in the development of SC-CO₂ techniques for particulate drug delivery systems is discussed in detail. Additionally, future perspectives and limitations of SC-CO₂-based techniques in industrial applications are examined.

Reactive oxygen species (ROS) are important markers for understanding the cellular condition in the context of diseases and inflammatory reactions to nanoparticle uptake. Their precise localization in the cellular context by high resolution microscopy, such as Transmission Electron Microscopy, is an essential tool to visualize ultrastructural alterations and the formation of ROS. However, till now, only limited staining strategies for the TEM investigation of ROS are applied to identify them into the cellular context which are moreover associate to inherent problems of the staining procedure, such as high toxicity and unspecific precipitation in certain cultivation media. Here we report the development of a novel sensor particle system, which allows intracellular detection of ROS. These sensor particles link cerium chloride to the surface of a poly(2-vinylpyridine) particle which greatly decreased the cytotoxicity of cerium chloride to polymorphonuclear leukocytes and expands the choice of possible cultivation media This significantly improves the literature known staining protocols for the detection of ROS by transmission electron microscopy. The formation of ROS is indicated by the formation of a characteristic needle-like precipitate on the nanoparticles’ surface.