Comparing Zwitterionic and PEG Exteriors of Polyelectrolyte Complex Micelles

Abstract

A series of model polyelectrolyte complex micelles (PCMs) was prepared to investigate the consequences of neutral and zwitterionic chemistries and distinct charged cores on the size and stability of nanocarriers. Using aqueous reversible addition-fragmentation chain transfer (RAFT) polymerization, we synthesized a well-defined diblock polyelectrolyte system, poly(2-methacryloyloxyethyl phosphorylcholine methacrylate)-block-poly((vinylbenzyl) trimethylammonium) (PMPC-PVBTMA), at various neutral and charged block lengths to compare directly against PCM structure–property relationships centered on poly(ethylene glycol)-block-poly((vinylbenzyl) trimethylammonium) (PEG-PVBTMA) and poly(ethylene glycol)-block-poly(l-lysine) (PEG-PLK). After complexation with a common polyanion, poly(sodium acrylate), the resulting PCMs were characterized by dynamic light scattering (DLS) and small angle X-ray scattering (SAXS). We observed uniform assemblies of spherical micelles with a diameter ~1.5–2× larger when PMPC-PVBTMA was used compared to PEG-PLK and PEG-PVBTMA via SAXS and DLS. In addition, PEG-PLK PCMs proved most resistant to dissolution by both monovalent and divalent salt, followed by PEG-PVBTMA then PMPC-PVBTMA. All micelle systems were serum stable in 100% fetal bovine serum over the course of 8 h by time-resolved DLS, demonstrating minimal interactions with serum proteins and potential as in vivo drug delivery vehicles. This thorough study of the synthesis, assembly, and characterization of zwitterionic polymers in PCMs advances the design space for charge-driven micelle assemblies.

Physical Property Scaling Relationships for Polyelectrolyte Complex Micelles

“…Again, by analyzing each polymer length individually while the others remain constant, we determined P AB µN A -0.79±0.31 , P C µN A -0.79±0.31 , P AB µN B 1.38±0.41 , P C µN B 2.38±0.41 , P AB µN C -0.21±0.25 , P C µN C -1.21±0. 25 . We estimate within error that P AB is independent of N C and P C decreases linearly with N C .…”

Physical Property Scaling Relationships for Polyelectrolyte Complex Micelles

“…41 , and N C -0.21±0. 25 , as shown in Figure 4. Trends for n ip are synergistic with those of R core : both decrease as N A increases, increase as N B increases, and are unaffected by changes in N C , but the rates of change are more drastic for n ip compared to R core .…”

“…In these situations, most PCMs have a core-corona spheroidal morphology, where the core contains the neutralized charged components (B+C), and the corona is formed from the neutral block (A). Poly(elthylene glycol) (PEG) is commonly used at the neutral component due to its availability and inertness in biological environments, but other net neutral polymers such as polyacrylamide 24 or zwitterionic polymers 25,26 have also shown promise. Charged components are generally biopolymers like polypeptides or nucleic acids, synthetic polyelectrolytes, or charged molecules like proteins or drugs.…”

100th Anniversary of Macromolecular Science Viewpoint: Attractive Soft Matter: Association Kinetics, Dynamics, and Pathway Complexity in Electrostatically Coassembled Micelles

“…Finally, we foresee an increasing effort from the polymer chemistry community to prepare and incorporate custom-tailored materials and substitute PEO by other stabilizers, such as zwitterionic/antifouling blocks, 117 to fine-tune the stability, responsivity, dynamicity, and functionality of C3Ms in vitro and in vivo for improved performance in complex (biological) environments.…”