Poly(2-oxazolines) in biological and biomedical application contexts
Introduction
Poly(oxazolines) have been the subject of a considerable amount of research since the 1960s [1], [2], [3], [4], [5], [6], [7], with a significant number of papers focusing on the polymerisation of 2-substituted oxazolines [8], [9], [10], [11]. Monomers substituted in the 4- or 5-position are more difficult to polymerise, due to steric crowding [11]. Polymerisations are usually carried out via a living cationic ring-opening mechanism (CROP), which yields well-defined polymers of narrow average molecular weight distributions (Fig. 1) [4], [6]. Furthermore, a large property space can theoretically be accessed, as the synthesis of 2-substituted monomers can be conveniently accomplished via condensation of a primary nitrile and 2-aminoethanol [9], [12]. Commercially, however, only 2-methyl, 2-ethyl, 2-isopropyl and 2-phenyl oxazoline are currently available.
Although the use of poly(2-oxazolines) in adhesive and coating formulations [13], [14], [15], as pigment dispersants in inks [16], and drug in delivery applications [17] has been documented, the polymers have not found widespread commercial application, as the (batch) polymerisations times range from several hours to several days [18], [19], [20], [21], [22], [23], [24], [25]. Recent advances in synthetic technology, notably the advent of microwave reactors, which allow easy access to high-temperature/high-pressure synthesis conditions, have allowed the acceleration of polymerisations by factors of up to 350, when compared with conventional reflux conditions, while reducing the occurrence of side reactions and maintaining the living character of the reaction [26].
Another attractive feature of polyoxazolines is the ease of preparation of copolymers, notably block copolymers [27], [28], [29], [30], but also of star-shaped [29], [31], [32] and hyperbranched [33], [34] motives as well as cross-linked networks [35]. Block copolymers generally provide easy access to amphiphiles, which, provided the blocks are judiciously chosen, are capable of self-assembly to form a variety of complex structures, such as (multicompartment) micelles [36] and vesicles [37], [38].
Due to the versatility of this class of polymer and their ability to form functional materials and nanostructures, the interest in poly(2-acyl-2-oxazoline)-based materials is rising. Furthermore, this class of materials could be promising for use in biomedical applications, but is under-researched and under-utilized in this context at present. The aim of this paper is to provide a general overview over “the state of the art” in poly(oxazoline) research in biological and biomedical application areas, roughly covering the last decade of research.
Section snippets
Poly(2-oxazolines) in biological application contexts
One of the principal application areas for polymers in biological and medicinal contexts is drug and gene delivery [39], [40]. In the simplest case, a drug is enclosed in a polymeric matrix and released over time through diffusion [41]. Alternatively, complex multifunctional polymers with covalently attached drug moieties are constructed [42]. The combination of a polymer with a drug molecule has several main advantages over the use of a pure drug molecule: (1) potentially increased solubility
Summary and conclusion
Polyoxazoline-based or polyoxazoline-derived polymers clearly have a significant application potential in a large number of technological contexts, whether this be the formation of stealth liposomes, or of membrane structures and containers which allow the incorporation of functional proteins, thus mimicking natural systems, or whether it is the use of polyoxazoline-based polymers as carriers of drugs or as synthetic vectors and antimicrobial materials. When this broad application range is
Acknowledgement
The authors wish to acknowledge the Dutch Polymer Institute (DPI), Project #500 for financial support of this work.
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