| Amphiphilic polymers are macromolecules that simultaneously contain hydrophobic and hydrophilic components. These molecules not only attract much attention in academic research but also are important materials in industry. Application areas include detergency, oil field, paints, agriculture, food, cosmetics, and pharmaceutics. This dissertation highlights my efforts since the November of 2007 on three separate systems of amphiphilic polymers, which addresses both the fundamental self-assembly behavior in solution and applications in pharmaceutical formulation. Chapter 2 describes the self-assembled micelles in water that contain semicrystalline polyethylene (PE) as the core-forming material. Poly(N,N-dimethylacrylamide)-polyethylene (AE) diblock copolymers were chosen as the model system. An AE diblock copolymer with relatively low PE composition resulted in micelles with oblate ellipsoidal cores in water, in which crystalline PE existed as flat disks at the center and rubbery PE resided on both sides. In contrast, a control sample with a rubbery polyolefin as the hydrophobic component resulted in micelles with spherical cores in water. The morphology transition was ascribed to the crystallization of PE. The heat-assisted direct dissolution for sample preparation was identified as a stepwise "micellization-crystallization" procedure. In addition, the morphology of the aggregates exhibited much dependence on the composition of AE copolymers, and wormlike micelles and bilayered vesicles were obtained from samples with relatively high PE compositions. Chapter 3 demonstrates the precise synthesis of glucose-containing diblock terpolymers from a combination of anionic and reversible addition-fragmentation chain-transfer (RAFT) polymerizations. The resulting micelles exhibited excellent stability in several biologically-relevant media under in vitro conditions, including 100% fetal bovine serum. These particles may find applications as serum-stable nanocarriers of hydrophobic drugs for intravenous administration. Chapter 4 presents the development of novel cellulose derivatives as matrices in amorphous solid dispersions for improving the bioavailability of poorly water-soluble drugs in oral administration. Hydroxypropyl methylcellulose (HPMC) was modified with monosubstituted succinic anhydrides using facile anhydride chemistry, and the resulting materials simultaneously contained hydrophobic, hydrophilic, and pH-responsive moieties. Several HPMC esters of substituted succinates exhibited more effective crystallization inhibition of phenytoin under in vitro conditions than a commercial hydroxypropyl methylcellulose acetate succinate (HPMCAS). |
