Tuning the Morphology of Block Copolymer-Based pHtriggered Nanoplatforms as Driven by Changes in Molecular Weight and Protocol of Manufacturing

The ability to tune size and morphology of self-assemblies is particularly relevant in the
development of delivery systems. By tailoring such structural parameters, one can provide
larger cargo spaces or produce nanocarriers that can be loaded by hydrophilic and hydrophobic
molecules starting ideally from the same polymer building unit. We herein demonstrate that the
morphology of block copolymer-based pH-triggered nanoplatforms produced from poly(2-
methyl-2-oxazoline)m-b-poly[2-(diisopropylamino)-ethyl methacrylate]n (PMeOxm-b-PDPAn)
is remarkably influenced by the overall molecular weight of the block copolymer, and by the
selected method used to produce the self-assemblies. Polymeric vesicles were produced by
nanoprecipitation using a block copolymer of relatively low molecular weight (Mn ~ 10 kg.mol-
1). Very exciting though, despite the high hydrophobic weight ratio (wPDPA > 0.70), this method
conducted to the formation of core-shell nanoparticles when block copolymers of higher
molecular weight were used, thus suggesting that the fast (few seconds) self-assembly
procedure is controlled by kinetics rather than thermodynamics. We further demonstrated the
formation of vesicular structures using longer chains via the solvent-switch approach when the
“switching” to the bad solvent is performed in a time scale of a few hours (approximately 3 hs).
We accordingly demonstrate that using fairly simple methods one can easily tailor the
morphology of such block copolymer self-assemblies, thereby producing a variety of
structurally different pH-triggered nanoplatforms via a kinetic or thermodynamicallycontrolled
process. This is certainly attractive towards the development of nanotechnologybased
cargo delivery systems.