Stable self-assemblies of polyhydroxybutyrate-based diblock and triblock copolymers nanoprecipitated in water: influence of their hydrophilic weight fraction

Abstract

Polyester-based amphiphilic block copolymers are the most widely investigated ones for biomedical applications, and in particular as drug delivery systems. Self-assemblies derived from such biocompatible and biodegradable copolymers are most often centered on poly(lactic acid), poly(glycolic acid), poly(lactic acid-co-glycolic acid), or poly(-caprolactone), and commonly involve the use of a surfactant during their elaboration. Herein, we report the use of nanoprecipitation rather than surfactant-assisted self-assembling based on biocompatible and biodegradable polyhydroxyalkanoates (PHAs), namely poly(3-hydroxybutyrate) (PHB)  the ubiquitous PHA, and poly(-malic acid) (PMLA). Analogous diblock PMLA-b-PHB and triblock PMLA-b-PHB-b-PMLA copolymers were comparatively explored. Tuning both the hydrophilic weight fraction f (i.e., the PMLA content) and the polymer topology enabled to design a range of PHA-type nano-objects, as investigated and rationalized through light scattering measurements. While large aggregates (Rh ca. 300 nm) were obtained in aqueous solutions from PMLA-b-PHB copolymers exhibiting a low hydrophilic weight fraction (f ca. 10%), well-defined spherically shaped core-shell micelles (Rh ca. 1030 nm) were prepared from diblock copolymers with higher f values (ca. 5076%). Triblock copolymers within such a similar f range (ca. 1582%) formed smaller aggregates (Rh ca. 20to26 nm) distinct from the better-defined core-shell micelles recovered from the diblock copolymers. Furthermore, blending two f-distinct diblock copolymers resulted in self-assembled systems displaying characteristics (Rh ca. 53 to 67 nm) intermediate to those of the pristine copolymers, thus supporting the co-assembly of the two diblock copolymers within the same particles. Finally, the structure of the copolymers is shown to enable tailoring the stability and resilience of their self-assemblies upon ageing in physiological-like conditions.