Amphiphilic block copolymer micelles : creation of functional nanocavities and their use as nanocontainers for controlled release

Abstract

Block copolymers in solution can self-assemble in to a variety of morphologies, with features on the nanometer length scale. This has lead to significant recent research into this assembly process and a wide range of potential applications. The exchange of block copolymer molecules between micelles and solution is very slow compared to the exchange kinetics observed for low molecular weight surfactant micelles. A favorable result of these slow exchange kinetics is the ability to retain a micellar morphology during casting from selective solvents onto solid substrates; this morphology becomes kinetically trapped in the final thin film upon solvent evaporation, even in cases for which the copolymer composition would suggest a transition to a different equilibrium heterogeneous phase. Control of the structural parameters of the micellar thin films, including micelle core size, micelle corona size and distance between adjacent micelle cores is important for thin film applications. Here we demonstrate the ability to control these structural parameters using polystyrene-block-poly(acrylic acid) (PS-b-PAA) as a model block copolymer system that assembles into spherical micelles in toluene. Several strategies were employed: varying the block copolymer molecular weight, adding PS homopolymer into the micellar solution, and also by the combination of different micellar solutions. Patterning of micelle films on the micron length scale is accomplished via two PDMS stamp-based soft lithographic techniques. PS-b-PAA spherical micelle thin films cast from toluene can undergo rearrangement upon exposure to solvents selective for the PAA block. The solvent swells the PAA micelle core and ruptures the glassy PS corona, a process we termed cavitation. Here we have investigated the conditions required for this cavitation process to occur and the end-state polymer morphology of close-packed films of PS-b-PAA micelles following treatment with a series of short alkyl chain alcohols or aqueous solutions of varying pH and ionic strength. In addition to the effects of solvent conditions, we show that the cavitation process is influenced by the molecular weight of the PS block and is thermally reversible.

(cont.) Following cavitation, the nanopatterned regions of exposed PAA are available for conjugation chemistry, demonstrated here through selective linking of a fluorescently labeled protein. Cavitation was also observed in polystyrene-block-poly(2vinyl pyridine) (PS-b-P2VP) spherical and cylindrical micelles. Biocompatible oils are used in a variety of medical applications ranging from vaccine adjuvants to vehicles for oral drug delivery. To enable such nonpolar organic phases to serve as reservoirs for delivery of hydrophilic compounds, we explored the ability of block copolymer micelles in organic solvents to sequester proteins for sustained release across an oil-water interface. Self-assembly of the block copolymer, poly (ecaprolactone)-block-poly(2-vinyl pyridine) (PCL-b-P2VP), was investigated in toluene and oleic acid, a biocompatible naturally- occurring fatty acid. Micelle formation in toluene was characterized by dynamic light scattering (DLS) and atomic force microscopy (AFM) imaging of micelles cast onto silicon substrates. Cryogenic transmission electron microscopy confirmed a spherical morphology in oleic acid. Studies of homopolymer solubility implied that micelles in oleic acid consist of a P2VP corona and a PCL core, while P2VP formed the core of micelles assembled in toluene. The loading of two model proteins (ovalbumin (ova) and bovine serum albumin (BSA)) into micelles was demonstrated with loadings as high as 7.8 % wt of protein per wt of P2VP in oleic acid. Characterization of block copolymer morphology in the two solvents after protein loading revealed spherical particles with similar size distributions to the asassembled micelles. Release of ova from micelles in oleic acid was sustained for 30 hours upon placing the oil phase in contact with an aqueous bath. Unique to the situation of micelle assembly in an oily phase, the data suggest protein is sequestered in the P2VP corona block of PCL-b-P2VP micelles in oleic acid. More conventionally, protein loading occurs in the P2VP core of micelles assembled in toluene.