Block Copolymer Solutions: Transport and Dynamics, Targeted Cargo Delivery, and Molecular Partitioning and Exchange

Block copolymers have been extensively applied in diverse fields including packaging, electrolytes, delivery devices, and biosensors. Multiple investigations have been carried out on polymeric materials for cargo delivery purpose to understand how they behave over time. Block copolymer micelles (BCMs) have demonstrated superiority to deliver cargo, especially in drug delivery due to their encapsulation of hydrophobic agents. This dissertation will mainly study BCMs for potential applications in cargo delivery.

Methods to study BCMs, including NMR spectroscopy, relaxometry and diffusometry, can provide valuable molecular information, such as chemical structure, translational motion, inter- or intramolecular interaction, dynamics, and exchange kinetics. Therefore, this dissertation describes applications of versatile NMR methods to reveal the fundamental behaviors of block copolymer self-assemblies, such as their dynamic stability, cargo partitioning, polymer chain exchange, and chain distribution in solution.

We have investigated two BCM systems. Poly(ethylene oxide)-b-(ε-caprolactone) (PEO-PCL) is a model system to study BCM dynamic stability. PEO-PCL can self-assemble into spherical micelles at 1% w/v in D2O-THF-d8 mixed solvents. We used NMR diffusometry to quantify diffusion coefficients and populations of micelles and unimers (i.e. free polymer chains in solution) over a range of temperature (21 – 50 °C) and solvent composition (10 – 100 vol % THF-d8). By mapping the micelle-unimer coexistence phase diagrams, we are able to enhance our ability to understand and design micelle structure and dynamics. Moreover, we can also probe the chain exchange kinetics between micelles using a new technique we developed – time-resolved NMR spin-lattice relaxation (T1) or TR-NMR. This technique is an analog to time-resolved small-angle neutron scattering (TR-SANS), which can monitor specific signal intensity changes caused after mixing of isotope-labeled micelle solutions.

A second system, Pluronic® F127 (PEO99PPO69PEO99) is a test system to study BCM structure and dynamic changes upon drug uptake. Pluronic® F127 is a commercial copolymer that can solubilize different hydrophobic drugs in micelles. We successfully encapsulated three model drugs into Pluronic® F127 BCMs and investigated the effects of polymer concentration and drug composition on drug partitioning fractions. Also, we proposed to design and synthesize a series of block copolymers with varied glass transition temperatures in core-forming blocks. Using NMR diffusometry, we have measured the existing unimer concentrations in micellar solutions and correlated these results with chain mobility and internal chemical composition.

Lastly, we have extended our expertise in NMR and polymers into the study of ion-containing polymer systems (polyelectrolytes). A critical problem in polymer science is the inability to reliably measure the molecular weight of polyelectrolytes. We are developing methods to solve this problem by using NMR diffusometry, rheology, scattering, and scaling theories to accomplish general molecular weight measurements for polyelectrolytes.

In short, this dissertation describes studies to provide more perspectives on structural and dynamic properties at various time and length scales for polymeric materials. NMR measurements, in combination with many other advanced techniques, have given us a better picture of soft matter behaviors and provided guidance for synthesis and processing efforts, especially in block copolymer micelles for delivery purposes.