Effect Of Confined Impinging Jet Mixing Processing Parameters On Poly (Lactic Acid) Nanoparticle Morphology

Biodegradable nanoparticles are at the forefront of drug delivery research as they provide numerous advantages over traditional drug delivery methods. An important factor affecting the ability of nanoparticles to circulate within the blood stream and interact with cells is their morphology. In this study a novel processing method, confined impinging jet mixing, was used to form poly (lactic acid) nanoparticles through a solvent-diffusion process with Pluronic F-127 being used as a stabilizing agent. This study focused on the effects of Reynolds number (flow rate), surfactant presence in mixing, and polymer concentration on the morphology of poly (lactic acid) nanoparticles. In addition to looking at the parameters affecting poly (lactic acid) morphology, this study attempted to improve nanoparticle isolation and purification methods to increase nanoparticle yield and ensure specific morphologies were not being excluded during isolation and purification. The isolation and purification methods used in this study were centrifugation and a stir cell. This study successfully produced particles having pyramidal and cubic morphologies. Despite successful production of these morphologies the yield of non-spherical particles was very low, additionally great variability existed between redundant trails. Surfactant was determined to be very important for the stabilization of nanoparticles in solution but appears to be unnecessary for the formation of nanoparticles. Isolation and purification methods that produce a high yield of surfactant free particles have still not been perfected and additional testing will be necessary for improvement.¿

The Effects of Pi-Pi Stacking on the Controlled Radical Polymerization of Vinyl Aromatics

The atom transfer radical polymerization (ATRP) of styrene (St) was conducted in the presence of varying equivalence (eq) of hexafluorobenzene (HFB) and octafluorotoluene (OFT) to probe the effects of pi-pi stacking on the rate of the polymerization and on the tacticity of the resulting polystyrene (PSt). The extent of the pi-pi stacking interaction between HFB/OFT and the terminal polystyrenic phenyl group was also investigated as a function of solvent, both non-aromatic solvents (THF and hexanes) and aromatic solvents (benzene and toluene). In all cases the presence of HFB or OFT resulted in a decrease in monomer conversion indicating a reduction in the rate of the polymerization with greater retardation of the rate with increase eq of HFB or OFT (0.5 eq to 1 eq HFB/OFT compared to St). Additionally, when aromatic solvents were used instead of non-aromatic solvents the effect of the HFB/OFT on the rate was minimized, consistent with the aromatic solvent competitively interacting with the HFB/OFT. The effects of temperature and ligand strength on the ATRP of St in the presence of HFB were also probed. It was found that when using N,N,N’,N’,N’’-pentamethyldiethylenetriamine (PMDETA) as the ligand the effects of HFB at 38o were the same as at 86oC. When tris[2-(dimethylamino)ethyl]-amine (Me6TREN) was used as the ligand at 38o there was a decrease in monomer conversion similar to the analogous PMDETA reaction. When the polymerization was conducted at 86oC there was no effect on the monomer conversion with HFB present compared to when HFB was absent. To investigate the pi-pi stacking effect even further, the reverse pi-pi stacking system was observed by conducting the ATRP of pentafluorostyrene (PFSt) in the presence of varying eq of benzene and toluene, which in both cases resulted in an increase in monomer conversion compared to when benzene or toluene were absent; in summary the rate of the ATRP of PFSt increases when benzene or toluene waas present in the reaction. The pi-pi stacking interaction between the HFB/OFT and the dormant alkyl bromide of the polymer chain was verified by 1H-NMR with 1-bromoethylbenzene as the alkyl bromide. Also verified by 1H-NMR was the interaction between HFB/OFT and St and the interaction between PFSt and benzene. In all 1H-NMR spectra a perturbation in the aromatic and/or vinyl peaks was observed when the pi-pi stacking agent was present compared to when it was absent. The tacticity of the PSt formed in the presence of 1 eq of HFB was compared to the PSt formed in the absence of HFB by observing the C1 signal in their 13C-NMR spectra, but no change in shape or chemical shift of the signal was observed indicating that there was no change in tacticity.

Dimerization of Poly(methyl methacrylate) Chains Using Radical Trap-Assisted Atom Transfer Radical Coupling

End-brominated poly(methyl methacrylate) (PMMABr) was prepared by atom transfer radical polymerization (ATRP) and employed in a series of atom transfer radical coupling (ATRC) and radical trap-assisted ATRC (RTA-ATRG) reactions. When coupling reactions were performed in the absence of a nitroso radical trap-traditional ATRC condition-very little coupling of the PMMA chains was observed, consistent with disproportionation as the major termination pathway for two PMMA chain-end radicals in our reactions. When 2-methyl-2-nitrosopropane (MNP) was used as the radical trap, coupling of the PMMA chains in this attempted RTA-ATRC reaction was again unsuccessful, owing to capping of the PMMA chains with a bulky nitroxide and preventing further coupling. Analogous reactions performed using nitrosobenzene (NBz) as the radical trap showed significant dimerization, as observed by gel permeation chromatography (GPC) by a shift in the apparent molecular weight compared to the PMMABr precursors. The extent of coupling was found to depend on the concentrion of NBz compared to the PMMABr chain ends, as well as the temperature and time of the coupling reaction. To a lesser extent, the concentrations of copper(I) bromide (CuBr), nitrogen ligand (N,N,N',N',N"-pentamethyldiethylenetriamine = PMDETA), and elemental copper (Cu) were also found to play a role in the success of the RTA-ATRC reaction. The highest levels of dimerization were observed when the coupling reaction was carried out at 80 degrees C for 0.5h, with ratio of 1:4:2.5:8:1 equiv of NBz: CuBr:Cu:PMDETA:PMMABr.