Advances in amphiphilic polylactide/vinyl polymer based nano-assemblies for drug delivery

Micelles from self-assembled amphiphilic copolymers are highly attractive in drug delivery, due to their small size and hydrophilic stealth corona allowing prolonged lifetimes in the bloodstream and thus improved drug bioavailability. Polylactide (PLA)-based amphiphilic copolymer micelles are key candidates in this field, owing to the well-established biodegradability and biocompatibility of PLA. While PLA-b-poly(ethylene glycol) (PEG) block copolymer micelles can be seen as the gold standard in drug delivery research so far, the progresses in controlled radical polymerizations (Atom Transfer Radical Polymerization, Reversible Addition-Fragmentation Transfer and Nitroxide Mediated Polymerization) have offered new opportunities in the design of advanced amphiphilic copolymers for drug delivery due to their flexibility in many regards: (i) they can be easily combined with ring-opening polymerization (ROP) of lactide, with a diversity in types of architectures (e.g., block, graft, star), (ii) they allow (co)polymerization of a wide range of vinyl monomers, possibly circumventing PEG limitations, (iii) functionalization (with biomolecules or stimuli-cleavable moieties) is versatile due to end-group fidelity and copolymerization ability with reactive/functional comonomers. In this review, we report on the advances in the past decade of such amphiphilic PLA/vinyl polymer based nano-carriers, regarding key properties such as stealth character, cell targeting and stimuli-responsiveness.