The encapsulation of therapeutic compounds into nanosized delivery vectors has become an important strategy to improve efficiency and reduce side effects in drug delivery applications. Here, we report the synthesis of pH-sensitive nanogels, which are based on the monomer N-[(2,2-dimethyl-1,3-dioxolane)­methyl]­acrylamide (DMDOMA) bearing an acid cleavable acetal group. Degradation studies revealed that these nanogels hydrolyze under acidic conditions and degrade completely, depending on the cross-linker, but are stable in physiological environment. The best performing system was further studied regarding its release kinetics using the anticancer drug doxorubicin. In vitro studies revealed a good compatibility of the unloaded nanogel and the capability of the doxorubicin loaded nanogel to mediate cytotoxic effects in a concentration and time-dependent manner with an even higher efficiency than the free drug. Based on the investigated features, the presented nanogels represent a promising and conveniently prepared alternative to existing carrier systems for drug delivery.

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 (Tg, 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.

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Carboxylate-pillar[5]arene can be used to change the charge property and content of carboxylate group in nanogels by supramolecular host–guest interaction, which can tune the hydrolysis of the nanogels and encapsulation and release of doxorubicin.