Complex poly(ε-caprolactone)/poly(ethylene glycol) copolymer architectures and their effects on nanoparticle self-assembly and drug nanoencapsulation

Abstract

Abstract Well-defined amphiphilic PCL-PEG copolymers with complex molecular architectures were synthesized through a combination of Ring Opening Polymerization (ROP) and Atom Transfer Radical Polymerization (ATRP) and used to produce self-assembled nanoparticles for drug nanoencapsulation. By varying the functionality of the initiator used for the ATRP (i.e. linear, 4-armed or multifunctional brush macroinitiators), a library of comb-like and brush block copolymers were obtained with different structure, molecular weight, and number of PEG and PCL blocks. We investigated how these parameters influenced nanoparticle self-assembly in aqueous environment, as well as the ability to encapsulate and release hydrophobic therapeutic molecules. In particular, the hydrophobic corticosteroid dexamethasone, known as a therapeutic drug with anti-inflammatory and immunosuppressive effects, was chosen as a model. The results indicate that self-assembly, final particle size and drug loading can be tuned by designing a specific macromolecular architecture, which therefore represents a key feature for the design of efficient polymer nanocarriers for drug delivery.