Amphiphilic gradient copolymers represent a promising alternative to extensively used block copolymers due to their facile one-step synthesis by statistical copolymerization of monomers of different reactivity. Herein, an in-depth analysis is provided of micelles based on amphiphilic gradient poly(2-oxazoline)s with different chain lengths to evaluate their potential for micellar drug delivery systems and compare them to the analogous diblock copolymer micelles. Size, morphology, and stability of self-assembled nanoparticles, loading of hydrophobic drug curcumin, as well as cytotoxicities of the prepared nanoformulations are examined using copoly(2-oxazoline)s with varying chain lengths and comonomer ratios. In addition to several interesting differences between the two copolymer architecture classes, such as more compact self-assembled structures with faster exchange dynamics for the gradient copolymers, it is concluded that gradient copolymers provide stable curcumin nanoformulations with comparable drug loadings to block copolymer systems and benefit from more straightforward copolymer synthesis. The study demonstrates the potential of amphiphilic gradient copolymers as a versatile platform for the synthesis of new polymer therapeutics.

Centrale Lille Université de Lille CNRS Université Artois UMR 8181 UCCS Unité de Catalyse et Chimie du Solide Lille F 59000 France

Department of Chemistry and Technology of Organic Materials Polymers and Natural Compounds al Faraby Kazakh National University 71 al Faraby av Almaty 050040 Republic of Kazakhstan

Department of Chemistry Ångström Laboratory Uppsala University Lägerhyddsvägen 1 Uppsala Sweden

Department of Endocrinology Key Laboratory of National Health and Family Planning Commission for Male Reproductive Health National Research Institute for Family Planning Beijing 100081 China

Department of Physical and Macromolecular Chemistry Faculty of Science Charles University Hlavova 2030 Prague 2 128 40 Czech Republic

Experimental Hematology and Biochemistry Lab Beijing Institute of Radiation Medicine Beijing 100850 China

Jülich Centre for Neutron Science Forschungszentrum Jülich GmbH Lichtenbergstr 1 85748 Garching Germany

Pharmaceutical Sciences Laboratory and Turku Bioscience Center of Åbo Akademi University and Turku Bioscience Turku 20520 Finland

School of Pharmacy University of Reading Whiteknights Reading RG6 6DX UK

Supramolecular Chemistry Group Department of Organic and Macromolecular Chemistry Ghent University Krijgslaan 281 S4 Ghent B 9000 Belgium

Tampere University of Technology Korkeakoulunkatu 7 Tampere 33720 Finland

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