(609b) Self-Assembly of Hydrophobically-Patterned Charged Polypeptides for Drug Delivery
AIChE Annual Meeting
Wednesday, November 13, 2019 - 4:00pm to 4:20pm
Polyelectrolyte complexation is the result of the interaction of oppositely charged macromolecules in solution. Under precise conditions, these complexes can form liquid-liquid phase separated states called complex coacervates. The complex coacervate phase has a very low interfacial tension with water and therefore can be used as an encapsulant in the food and pharmaceutical industries. Here we design hydrophobically-patterned ionic polypeptides in order to systematically study the effect of hydrophobicity on complex behavior and to assess the ability of these hydrophilic materials to encapsulate hydrophobic drugs. Two generations of oppositely charged peptides are designed, containing non-charged amino acids of increasing hydrophobicity: glycine, alanine, and leucine; while lysine and glutamic acid are used as the charged amino acids for the polycation and polyanion sequences, respectively. Previous work with ionic polypeptides has determined that chirality is an important factor that controls the phase behavior of polypeptide complexes, where alternating patterns of L and D amino acids leads to complex coacervate formation, while homochiral sequences form solid precipitates. Therefore, here we use an alternating sequence of D and L-chiral amino acids in order to promote liquid coacervate formation. The first generation designs consist of D-charged residues and L-hydrophobic residues, while the second generation peptides, also have alternating chiral patterns, but a higher charge density. Peptide sequences are characterized using mass spectroscopy (MALDI-TOF), H NMR and circular dichroism (CD). The polypeptide based polyelectrolyte complexes are characterized using turbidity measurements to evaluate the extent of complex formation as well as the stability of the polyelectrolyte complexes against salt (NaCl) and temperature. In addition, optical microscopy and infrared spectroscopy are used to characterize complex phase behavior and secondary structure. Our results indicate that increasing hydrophobicity improves the stability of the complexes and increases the amount of complex formed with increasing temperature. Moreover, the density and amount of the complex phase are found to increase with hydrophobicity. We use a hydrophobic model dye to assess the encapsulation behavior of the complexes showing that encapsulation efficiency of the complexes increases as the hydrophobicity increases. This work provides insight for the potential application of these complexes in drug delivery containing both charged biological therapeutics and hydrophobic drugs.