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We describe a new approach to depot drug delivery in which a copolymer poly[N-isopropyl acrylamide-co-N-(3-imidazolylpropyl)methacrylamide] (PNIPAM-co-ImPM) is considered as the main object and matrix for a new formulation strategy that provides the controlled and sustained release of an incorporated drug. The relatively low content of ImPM groups (1.6 mol%) was determined to be sufficient to introduce pH-sensitive behavior to the polymer. Together with NIPAM units, which possess a thermo-sensitive behavior, a dual sensitivity was imparted to the polymer that was investigated by means of turbidimetry and dynamic light scattering. A change in pH from 9 down to 4 was observed to result in the increase of the polymer transition temperature from 32 to 70 °C. The separation process is also accompanied with the formation of ca. 150–300 nm particles while above the transition temperature. The pH value of approximately 6.5 was defined as a boundary value, where certain properties of the system significantly change. This observation assumes a potential attractiveness of the system for biological applications in which injection is possible using a liquid form at pH ca. 5 without the risk of injection needle obstruction. In this way, a depot is formed at the application site upon simultaneously heating to body temperature and increasing the pH to the physiological value of 7.4. An in vivo experiment using the polymer in PBS (pH = 5.0) with paliperidone as a model drug showed excellent results regarding the release of the drug from a depot. The putative mechanism of action for our depot system is thoroughly described in the article.

Poly(2-oxazoline)s (in literature abbreviated as PAOx, POx, or POZ, herein referred to as PAOx) represent an emerging class of biocompatible polymers outperforming polyethylene glycol (PEG) in many aspects, including their high synthetic versatility and structural modularity. In this review, we provide a brief introduction to PAOx chemistry and biology to sketch their potential in biomaterials science. Further, we provide a detailed comprehensive overview of the literature on PAOx-protein conjugates with emphasis on their critical evaluation and comparison with analogous systems based on PEG. Based on this literature overview, PAOx seem to be an excellent alternative to PEG in the construction of therapeutic polymer-protein conjugates.