(734a) Evaluating Corona Stabilization Effects in Thermo-Responsive Polyelectrolyte Complex Micelles

There is a large amount of interest in the use of polymeric/biomolecule macrostructures for drug delivery applications. The system investigated here is formed and solvated in water, preventing the need for physiologically toxic solvents. The use of thermally controlled components allows for precise control over release of cargo. Although a lot of progress has been made on targeting properties of drug delivery vehicles, obtaining release at a site of distress remains a challenge. Our work focuses on the formation of thermo-responsive polyelectrolyte complex (PEC) micelles as a model system to show encapsulation and release of charged molecules. PECs form by mixing two oppositely charged polymers in solution. This phenomenon results in either complex coacervation which is a liquid-liquid phase separation or solid precipitate formation. Electrostatic interaction between a diblock copolymer of a neutral block and a charged block, with an oppositely charged polymer leads to the formation of PEC micelles. The micelles formed have a polyelectrolyte complex core, while the neutral block forms the corona. PEC micelles have applications in nucleic acid delivery, where the negatively charged nucleic acid serves as the polyanion. This work explores using a thermosensitive polymer a poly(N-isopropyl acrylamide)(pNIPAM) as the neutral block. pNIPAM has a lower critical solubility temperature, above which a hydrophilic to hydrophobic transition occurs. This transition could lead to a core-corona inversion which could facilitate the release of molecules from within the polyelectrolyte core, leading to potential applications in controlled release drug delivery. We are characterizing micelles formed using a diblock copolymer of pNIPAM-poly(acrylic acid) with (1) poly(lysine) (Single-corona micelles) and (2) poly(ethylene glycol)-b-poly(lysine) (Dual-corona micelle) to investigate the effect of corona stabilization and micelle morphology, before and after temperature transition, including a comparison between a single-corona and a double-corona stabilized micelle. Dynamic light scattering, small angle x-ray scattering, absorbance spectroscopy, and electron microscopy are used to characterize micelle architecture as a function salt concentration, polymer concentration, charge ratio, and temperature, which are all parameters known to affect polyelectrolyte complex formation. We have shown that the single-corona micelles are worm-like, and the dual-corona micelles are spherical. The application of temperature (greater than the polymer LCST) causes the single-corona system to lose structural integrity, while the dual-corona system retains its morphology. The encapsulation and release of a charged dye molecule was also shown, elucidating the applicability of this thermo-responsive system to drug-delivery. Future work will involve the characterization of post-transition structure and release mechanics.