Poly(2‐oxazoline)‐ and Poly(2‐oxazine)‐Based Self‐Assemblies, Polyplexes, and Drug Nanoformulations—An Update

Abstract

For many decades, poly(2‐oxazoline)s and poly(2‐oxazine)s, two closely related families of polymers, have led the life of a rather obscure research topic with only a few research groups world‐wide working with them. This has changed in the last five to ten years, presumably triggered significantly by very promising clinical trials of the first poly(2‐oxazoline)‐based drug conjugate. The huge chemical and structural toolbox poly(2‐oxazoline)s and poly(2‐oxazine)s has been extended very significantly in the last few years, but their potential still remains largely untapped. Here, specifically, the developments in macromolecular self‐assemblies and non‐covalent drug delivery systems such as polyplexes and drug nanoformulations based on poly(2‐oxazoline)s and poly(2‐oxazine)s are reviewed. This highly dynamic field benefits particularly from the extensive synthetic toolbox poly(2‐oxazoline)s and poly(2‐oxazine)s offer and also may have the largest potential for a further development. It is expected that the research dynamics will remain high in the next few years, particularly as more about the safety and therapeutic potential of poly(2‐oxazoline)s and poly(2‐oxazine)s is learned.

Self-Organization in Dilute Aqueous Solutions of Thermoresponsive Star-Shaped Six-Arm Poly-2-Alkyl-2-Oxazines and Poly-2-Alkyl-2-Oxazolines

“…These facts allow the estimation of the aggregation degree magg as the ratio of volumes of the aggregates and the macromolecules. For spherical particles, the volume is proportional to third power of their radius and for investigated CPh6-PAlOx magg ≈ (Rm/Rh-D) 3 (1)…”

“…Thermoresponsive pseudo-polypeptoids have attracted great interest of researchers in recent years due to the wide potential of their application, for example, in medicine as nanocontainers for targeted delivery of drugs [ 1 , 2 , 3 ]. For them, the synthesis conditions were determined, allowing obtaining polymers with a given structure and molar mass characteristics.…”

Tuning the Thermogelation and Rheology of Poly(2-Oxazoline)/poly(2-Oxazine)s Based Thermosensitive Hydrogels for 3D Bioprinting.

“…An appropriate scaffold should provide a room for homogeneous distribution of cells, should be cyto-compatible, non-toxic and promote the cell's proliferation and differentiation. The generally excellent cyto-compatibility of POxbased polymers has been repeatedly shown while POzi-based polymers were studied to a lesser extent [22,29,34,66,90]. The cyto-compatibility of a certain polymer class must be assessed based on a defined set of experiments, cell-type and should never be generalized but rather verified on case by case basis.…”

“…Polymers of cyclic imino ethers, particularly poly(2-oxazoline)s (POx) and poly(2-oxazine)s (POzi) [19] with a thermoresponsive profile [20,21] have attained significant attention in the past decade [21,22]. POx has shown huge potential in tissue engineering [23][24][25][26], drug delivery [27][28][29][30][31][32][33] and 3D (bio) printing [22,34]. They are structural isomers of polypeptides, are synthetically relatively easily accessed and are highly tunable in their physico-chemical characteristics [35].…”

Tuning the Thermogelation and Rheology of Poly(2-Oxazoline)/Poly(2-Oxazine)s Based Thermosensitive Hydrogels for 3D Bioprinting

“…Polymers of cyclic imino ethers, particularly poly(2-oxazoline)s (POx) and poly(2-oxazine)s (POzi) [ 21 ] with a thermoresponsive profile [ 22 , 23 ] have attained significant attention in the past decade [ 23 , 24 ]. POx has shown huge potential in tissue engineering [ 25 , 26 , 27 , 28 , 29 ], drug delivery [ 30 , 31 , 32 , 33 , 34 , 35 ] and 3D (bio) printing [ 24 , 36 ]. They are structural isomers of polypeptides, are synthetically relatively easily accessed and are highly tunable in their physico-chemical characteristics [ 37 ].…”