Self-assembled nanoparticles of PEG and poly(2-oxazoline) based lactide block copolymers

Access to self-assembled nanoparticles has become increasingly vital for the development of next generation adjuvants for the delivery of nucleic acid therapeutics. However, the block ratio of amphiphilic block copolymers plays a significant role in achieving the desired architectures and in some cases coformulation of two different block copolymers is needed. Herein, we introduce an elegant approach to self-assembled stomatocytes and cubosomes through coformulation of PEG and poly(2-oxazoline) (POx) based lactide diblock copolymers. A series of well-defined POx macroinitiators and their block copolymers with D,L-lactide (PDLLA) has been synthesized and achieved narrow polydispersity indices at high monomer conversions. Thermal analysis of block copolymers indicated tunable glass transition temperatures (Tg) ranging from 33 degrees C to 56 degrees C. Other critical factors influencing the structure of the nanoparticle included the ratio of POx-PDLLA and PEG-PDLLA blocks as well as the hydrophobicity of the POx block. Moreover, DLS and cryo-TEM analysis revealed the formation of diverse nanostructures, namely stomatocytes, pseudo-vesicles, and possibly cubosomes. This versatile platform allows for precise control over nanoparticle shapes by adjusting block lengths and coformulation ratios. This highlights the potential of using coformulations in biomedical applications, enabling the rational design of advanced nanomaterials with tailored functionalities for specific targets.