Síntese e caracterização de cápsulas poliméricas responsivas

Abstract

Block copolymers based on 2-ethyl-2-oxazoline (EtOx), 4-vinylpyridine (4VP) and 4-vinylbenzoic acid (4VBA) were synthesized and studied regarding the self-assembly in aqueous medium and the pH-responsiveness. Poly(2-ethyl-2-oxazolines), PEtOx, with predetermined degrees of polymerization and molar mass dispersity (Đ) ≈ 1.1, prepared by the cationic ring-opening polymerization of EtOx and functionalized with 2-bromo-2methylpropionate, were used as macroinitiators for the atom radical transfer polymerization of 4VP or 4VBA. Two series of copolymers were produced: P(EtOx-b-4VP) and P(EtOx-b-4VBA) copolymers with 4VP and 4VBA molar fractions in the range of 0.40 -0.71 and 0.42 and 0.82, respectively. The critical micellar concentration of the P(EtOx-b-4VP) and P(EtOxb-4VBA) copolymers in aqueous medium varied between de 5 x 10 -4 to 3,75 x 10 -3 mg mL -1 and 1,7 x 10 -3 to 5 x 10 -3 , respectively. Aggregates of P(EtOx-b-4VP) were prepared by titration of a DMF solution with water and by adjusting the pH of the solution. The copolymers of this series self-assembled in micelles, worm-like micelles and vesicles, depending on the composition and method of preparation. The solvent switch procedure was adopted for the P(EtOx-b-4VBA) series and resulted in heterogeneous aggregates with a PEtOx-rich surface, their formation being dependent on the non-solvent addition rate. P(EtOx-b-4VBA) were not obtained by the pH adjustment method. P(EtOx-b-4VP) and P(EtOx-b-4VBA) aggregates could be loaded with Nile red. Even in conditions which P4VP and P4VBA block are ionized and water soluble, at pH = 2 and pH = 12 for P(EtOx-b-4VP) and P(EtOx-b-4VBA), respectively, the loading was observed. Vesicles and a mixture of vesicles and micelles of P(EtOx-b-4VP) were crosslinked with 1,4-dibromobutane and Cu 2+ .The hydrolytic stability, the pH-responsiveness and the redispersibility of freeze-dried aggregates were affected by the nature of the crosslinked and the crosslinking density. The crosslinked aggregates could be loaded with Reichardt's dye in aqueous medium at pH = 7, and with Nile red at pH = 7 and 2; at pH = 2 both blocks are swollen with water. Dextran (molar mass = 10 kDa), encapsulated in the aggregates during the self-assembly followed by crosslinking, was released at pH = 2, due to the protonation of the P4VP block. These results indicate the potential application of the block copolymers and their aggregates on the loading and further release of hydrophobic and hydrophilic substances.