The use of liposomes for the delivery of therapeutic agents to tumor sites took a major step forward with the introduction of sterically stabilized liposomes (PEG-liposomes). Several research groups reported the increased localization of PEG-liposomes at tumor sites. Once PEG-liposomes reach these sites, it can be desirable to increase the rate of release of encapsulated compound(s). The use of radiation for this purpose is attractive, because it can be delivered in a spatially and temporally selective manner. An effective strategy for the photopertubation of PEG-liposomes relies on the photoinitiated polymerization of reactive lipids in the liposomal bilayer. Previous studies indicated that the inclusion of the photoreactive 1,2-bis[10-(2' ,4'-hexadienoyloxy)decanonyl]-sn-glycero-3-phosphocholine (bis-SorbPC17,17) among the lipids of PEG-liposomes had little effect on their permeability until the PEG-liposomes were exposed to UV light. Photoexposure increased the permeability of the PEG-liposomes 200-fold. Research in this dissertation was focused upon increasing the reactivity of PEG-liposomes to UV and ionizing radiations. Additionally, the most favorable formulations were then used for the encapsulation of chemotherapeutic compounds that are currently on the market. Results in this dissertation indicate the ability to encapsulate water soluble compounds with high efficiency and subsequently release those compounds with minimal UV light exposure and with ionizing radiation doses that approach therapeutic levels.

Two dendrimer cores that contain o-nitrobenzyl photolabile moieties have been synthesized from piperonal. Methylated core analogs undergo clean photocleavage as indicated by the evolution of isosbestic points in the UV spectra during photolysis and the observation of degradation products by ¹H NMR. These dendrimer cores serve as precursors to dendrimer-based photodegradable materials. Second generation benzyl aryl ether dendrimers have been synthesized and undergo clean photocleavage as indicated by the evolution of isosbestic points in the UV spectra during photolysis and the observation of degradation products by ¹H NMR. Two oligomeric models of disassembling dendrimers have been synthesized from vanillin and o-vanillin. The first system tests the para cleavage vector while the latter test cleavage through the ortho vector of dendrimer disassembly. These systems are used to test potential trigger groups prior to dendrimer synthesis due to their ease of synthesis. Each system shows clean cleavage when triggered by an allyloxy or o-nitrobenzyloxy trigger group as indicated by the evolution of isosbestic points in the UV spectra during disassembly and the observation of disassembly products by ¹H NMR. Dendrimers with a 2,4-branching motif have been synthesized. These dendritic systems have been triggered with and allyloxy group and undergo disassembly via both the ortho and para cleavage vectors simultaneously. Cleavage was noted by the evolution of an isosbestic point in the UV spectra during disassembly.

Supramolecular assemblies are composed of noncovalently associated molecules which organize in water to yield 2-D and 3-D architectures. Crosslinking polymerization of supramolecular assemblies provides an effective means to modify their chemical and physical properties. Two methods of characterizing crosslinked polymeric assemblies were developed. These techniques rely on experimentally observed changes in polymer solubility and assembly stability in the presence of nonionic surfactants. The results show an inefficient crosslinking mechanism in organized media compared to isotropic polymerization. Two models rationalizing the inefficient crosslinking observed in organized media were proposed. Symmetrical crosslinking agents were synthesized to test the models. These results suggest intramolecular memorialization is an important process in the efficiency of crosslinking. The polymerization of a heterobifunctional lipid with two polymerizable groups in the same acyl chain separated by a six carbon spacer yielded a novel linear ladder-like polymer architecture. The two reactive groups are in regions of different polarity allowing for the simultaneous, selective, and sequential polymerization depending on the initiation chemistry employed. A second heterobifunctional lipid was designed and synthesized with a longer spacer between the two reactive groups. Polymerization of vesicles gave stable polymeric vesicles. The results from the crosslinking and redox polymerization studies on 2-D assemblies were applied to the inverted hexagonal and bicontinuous cubic phases. Phase behavior is characterized before and after crosslinking polymerization principally by variable temperature ³¹NMR. γ-Initiated polymerization of bis-lipids was studied to evaluate their sensitivity to ionizing radiation. The reactive moiety effects the initial rate of polymerization, extent of polymerization, and inhibition by oxygen. A preliminary investigation of polymerizable ion-paired amphiphiles (IPA) showed polymerization methods commonly used for zwitterionic lipids can be applied to IPA. This is the first report of polymerization of reactive groups in the anionic acyl chain of an ion-paired amphiphile.

The synthesis of bicyclobutane and cyclobutene monomers has been studied for the past 30 years. The polymers of these monomers have shown to possess superior properties in comparison to their linear analogs. Current synthetic methods used for the preparation of bicyclobutane and cyclobutene monomers require high temperature, high pressure, a large number of steps, and handling of toxic materials. Generally the synthetic methods employed have given very low yields. Dipolar [2+2]-cycloaddition reactions between alkenes take place spontaneously when one alkene contains strong donor substituents and the other strong acceptor substituents. Our general synthetic scheme involved a [2+2]-cycloaddition to form cyclobutane derivatives containing an acidic proton at C₃ or C₂ and an electron donating substituent at C₁. Following transformation of the donor substituent to a leaving group, bicyclobutanes or cyclobutenes were formed by 1,3- or 1,2-elimination. Phosphite, acetal, and amide as electron-donor substituents in [2+2]-cycloaddition reactions with cyano- or ester-substituted electrophilic alkenes form a variety of cycloadducts.

The thermal stability of two distinct blended polymer systems was examined. A model for polyethylene was used to investigate the vulnerability of polyethylene to premature crosslinking in industrial crosslinking conditions. Careful experiments were conducted to gather evidence of the interaction between a peroxide crosslinking agent and a specific antioxidant additive. Multiple lines of evidence were combined to propose a complete mechanism of interaction between the two species. The mechanism was further tested and a hypothesis was proposed for the reduction in premature crosslinking exhibited when the two species are present in polyethylene blends. A specific aspect of the proposed mechanism warranted further investigation on its own. The acid-catalyzed degradation of the peroxide initiator was thoroughly investigated. The thermal degradation of polyvinyl chloride was also studied. Model compounds were reacted with carboxylates to determine the relative rates of stabilization at various polymer defect sites. These model studies were combined with weight loss and color change investigations of bulk polymer systems. The knowledge gained from the model and polymer studies allowed for the proposal and examination of two novel stabilizing salt systems. The efficacy of the new stabilizers is presented.

No description available.

The surface properties of quaternized poly(styrene-block-4-vinylpyridinium) AB block copolymers in monolayers spread at the air/water interface were thoroughly studied using the Langmuir film balance technique and microscopy techniques (i.e. transmission electron microscopy and atomic force microscopy). The effects of both molecular structure (i.e. chain lengths of the two blocks, alkyl chain length, and the counterion of the quaternizing agent) and the experimental parameters (i.e. measurement temperatures, salt species and salt concentrations in the aqueous subphase, compression rates, and hysteresis) on interfacial behaviour of the ionic block copolymers were explored. Optimum conditions for the deposition of polymer monolayers from a water surface to a solid substrate for the microscopy studies were also investigated. Evidence for novel surface micelle formation is presented. Three morphologies of surface micelles (i.e. plane, rod, and starfish) are identified for the block copolymers. The appearance of each morphology is found to be related only to the relative chain lengths of the two blocks. Methods of calculating aggregation numbers in starfish micelles are developed. A phase transition phenomenon is observed in surface pressure-area isotherms of the polymer monolayers. This phase transition is found to be related to the pressure-induced solubilization process of the quaternized poly(4-vinylpyridinium) hydrophilic block chains. A model of a starfish-to-jellyfish transition is introduced to describe this phase transition phenomenon.

Rheological and processing behavior of a number of linear low-density polyethylene(LLDPE)/low-density polyethylene (LDPE) blends was studied with emphasis on the effects of long chain branching. First, a linear low-density polyethylene (LL3001.32) was blended with four LDPE's having distinctly different molecular weights. At high LDPE weight fractions, DSC melting thermograms have shown three different polymer phases; two for the pure components and a third melting peak of co-crystals. Different rheological techniques were used to check the thermo rheological behavior of all blends in the melt state and the effect of long chain branching. It was found that all blends are miscible in the melt state at small LDPE concentrations. The elongational behavior of the blends was studied using a uniaxial extensional rheometer, SER. The blends exhibit strain hardening behavior at high rates of deformation even at LDPE concentrations as low as 1%, which suggests the strong effect of branching added by the LDPE component. On the other hand, shear rheology was found to be insensitive to detect addition of small levels of LDPE up to lwt%. The second set of blends prepared and studied consisted of two Ziegler-Natta LLDPE's (LL3001.32 and Dowlex2045G) and two metallocene LLDPE's(AffinityPL1840 and Exact 3128) blended with a single LDPE. In DSC melting thermograms, it was observed that blends with metallocence LLDPE's exhibit a single melting peak at all compositions; whereas the Ziegler-Natta blends exhibit three melting peaks at certain compositions. It was found also that the metallocene LLDPE's are miscible with the LDPE at all concentrations. On the other hand, the Ziegler-Natta LLDPE's were found to be miscible with LDPE only at small LDPE concentrations. The processing behavior of all blends with emphasis on the effects of long chain branches was also studied in capillary extrusion. The critical shear stresses for the onset of sharkskin and gross melt fracture are slightly delayed with the addition of LDPE into LLDPE. Furthermore, the amplitude of the oscillations in the stick-slip flow regime, known as oscillating melt fracture, were found to scale with the weight fraction of LDPE. Amounts as low as 1 wt% LDPE have a significant effect on the amplitude of pressure oscillations. These effects are clearly due to the presence of LCB. It is suggested that the magnitude of oscillations in the oscillating melt fracture flow regime can be used as a method capable to detect low levels of LCB. Finally, the sharkskin and stick-slip polymer extrusion instabilities of a linear low-density polyethylene were studied as a function of the type of die geometry. The critical wall shear stress for the onset of flow instabilities, the pressure and flow rate oscillations, and the effects of geometry and operating conditions on the instabilities are presented for a LLDPE. It was found that sharkskin and stick-slip instabilities were present in the capillary and slit extrusion. However, stick-slip and sharkskin in annular extrusion are absent at high ratios of the inside to outside diameter of the annular die. This observation also explains the absence of these instabilities in polymer processing operations such as film blowing. These phenomena are explained in terms of the surface to volume ratio of the extrudates.

Kevlar fibers are known for their high strength. We have fluorinated these fibers in an attempt to increase their working temperature. Analysis shows that we are able to fluorinate a substantial amount of the aromatic ring, but loss to mechanical and thermal stability accompanies this. In the past, doping of polyacetylene film has shown to increase its conductivity by several orders of magnitude. In our efforts, we are also able to increase the conductivity of these films through direct fluorination. Our highest conductivity increase is approximately one order of magnitude. The fluorinated films show no increased resistance to air oxidation.

<p> This dissertation reports the synthesis and characterization of nanoscale coordination polymers (NCPs) for anticancer drug delivery. Nanoparticles have been explored in order to address the limitations of small molecule chemotherapeutics. NCPs have been investigated as drug delivery vehicles as they can exhibit the same beneficial properties as the bulk metal-organic frameworks as well as interesting characteristics that are unique to nanomaterials. </p><p> Gd-MTX (MTX = methotrexate) NCPs with a MTX loading of 71.6 wt% were synthesized and stabilized by encapsulation within a lipid bilayer containing anisamide (AA), a small molecule that targets sigma receptors which are overexpressed in many cancer tissues. Functionalization with AA allows for targeted delivery and controlled release to cancer cells, as shown by enhanced efficacy against leukemia cells. The NCPs were doped with Ru(bpy)₃²⁺ (bpy = 2,2'-bipyridine), and this formulation was utilized as an optical imaging agent by confocal microscopy. </p><p> NCPs containing the chemotherapeutic pemetrexed (PMX) were synthesized using different binding metals. Zr-based materials could not be stabilized by encapsulation with a lipid bilayer, and Gd-based materials showed that PMX had degraded during synthesis. However, Hf-based NCPs containing 19.7 wt% PMX were stabilized by a lipid coating and showed in vitro efficacy against non-small cell lung cancer (NSCLC) cell lines. Enhanced efficacy was observed for formulations containing AA. </p><p> Additionally, NCP formulations containing the cisplatin prodrug disuccinatocisplatin were prepared; one of these formulations could be stabilized by encapsulation within a lipid layer. Coating with a lipid layer doped with AA rendered this formulation an active targeting agent. The resulting formulation proved more potent than free cisplatin in NSCLC cell lines. Improved NCP uptake was demonstrated by confocal microscopy and competitive binding assays. </p><p> Finally, a Pt(IV) oxaliplatin prodrug was synthesized and incorporated in different NCPs using various binding metals. A moderate drug loading of 44.9 wt% was determined for Zr-based NCPs. This drug loading, along with a diameter less than 200 nm, make these particles promising candidates for further stabilization via lipid encapsulation.</p>