Design, synthesis and characterization of shell cross-linked nanoparticles (SCK's) containing degradable, crystalline, or glassy core domains

This dissertation work concerns the design, synthesis and characterization of shell cross-linked nanoparticles (SCK's) containing degradable, crystalline, or glassy core domains. Detailed studies of their physicochemical properties are described as well as potential biological applications.; Shell cross-linked nanoparticles (SCK's) have been developed as a new type of synthetic nanomaterials possessing an amphiphilic core-shell morphology consisting of a cross-linked hydrophilic shell and a hydrophobic core domain. This dissertation work focuses on the design, synthesis, and characterization of SCK's containing a hydrogel shell layer of poly(acrylic acid) crosslinked with 2,2′-(ethylenedioxy)bis(ethylamine) and containing different core domains composed of degradable, crystalline, or glassy polymeric materials. The effects of the core composition, the particle size, shape, and morphology on the physicochemical properties were studied by NMR (1H and 13C), FT-IR, and size exclusion chromatography (SEC) to determine the composition of the materials; atomic force microscopy (AFM), transmission electron microscopy (TEM), and dynamic light scattering (DLS) was used to determine particle dimensions and morphologies in both solid and solution states; differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) were used to probe the thermal properties of block copolymers and SCK's. These fundamental studies revealed highly interesting findings regarding the behavior of polymer chain segments covalently bound to a permeable crosslinked surface and confined to a nanoscopic volume.; SCK's containing degradable, crystalline, or glassy core domains were prepared via self-assembly of the corresponding amphiphilic diblock or triblock copolymer precursors into micelles followed by covalent cross-linking of the shell layer. The copolymer precursors, poly(ϵ-caprolactone)- b-poly(acrylic acid), poly(styrene)-b-poly(methylacrylate)- b-poly(acrylic acid), and poly(methylacrylate)-b-poly(styrene)- b-poly(acrylic acid), were prepared by various living polymerization methods, including ring-opening anionic and atom transfer radical polymerization. The entrapment of crystalline or glassy polymers in the core of SCK's provided unique systems for the study of crystallization and solution-state mobility of polymer chains in confined nanodomains. Extraction of the hydrophobic core polymers was accomplished by degradation or by a simple extraction of the chains to yield an inverted SCK structure. Removal of the poly(ϵ-caprolactone) degradable core by ester hydrolysis generated cage-like nanostructures. The inversion process allowed for the segmental organization in nanoparticles derived from shell crosslinked micelle templates to be studied. The potential application of SCK's as drug delivery system was also investigated.