Browsing by Subject "Micelle"

Now showing 1 - 3 of 3
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    Polymer Reservoirs to Solubilize Hydrophobic Drugs
    (2018-08) Li, Ziang
    Research and development of new drug delivery formulations for hydrophobic drugs hold great promise for patients worldwide in the ever-growing pharmaceutical industry. A large portion of the drugs, both in the current market and the development pipeline, suffer from low aqueous solubility, therefore limiting their efficacy for oral administration. One effective way to resolve this problem is the use of an amorphous solid dispersion (ASD), a blend of drug and polymer. An ideal polymer candidate can kinetically stabilize the dispersed drug in its amorphous form in the solid state, while enhancing drug solubility and dissolution in the solution state. Despite recent advances in polymer development for oral drug delivery, the structure-property relationships and the underlying solubility enhancement mechanisms are not fully understood for ASDs. The goals of this dissertation are to develop effective polymers for oral drug delivery, and more importantly, to elucidate the mechanism(s) of drug solubility and dissolution enhancement by using well-defined polymer platforms. Specifically, three model systems were designed and synthesized, including blends of a commercially available polymer and self-assembled micelles in Chapter 3, micelle-forming statistical copolymers and diblock polymers in Chapter 4, and chemically crosslinked polymer nanogels in Chapter 5. It was observed universally in all these three systems that hydrophobic drugs can be sequestered in the slightly hydrophobic polymer reservoirs, and that the drug-polymer partitioning is stronger when the polymer chains are more crowded. The partitioning inhibits drug nucleation and crystal growth in aqueous solution, resulting in enhanced drug solubility. This mechanism is supported by a battery of state-of-the-art characterization experiments, including light scattering, nuclear Overhauser effect and diffusion ordered spectroscopy, cryogenic transmission electron microscopy, small-angle X-ray scattering, and in vitro dissolution tests. Potential applications of the discovered mechanism and the characterization experiments to other drug/polymer systems are discussed as future directions.
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    Structure and Chain Exchange Kinetics of Block Copolymer Micelles in Selective Solvents
    (2017-08) Ma, Yuanchi
    Block copolymers can self-assemble into various structures, such as micelles and vesicles. Previous studies have shown that single chain exchange is the main mechanism for block copolymer micelles to achieve equilibrium. In this study, a new lower critical micelle temperature (LCMT) system, poly(methyl methacrylate)-block-poly(n-butyl methacrylate) in two room temperature ionic liquids, 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide and 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide was developed, and its chain exchange kinetics were investigated using time-resolved small-angle neutron scattering (TR-SANS). In order to probe the effect of the core block length, the corona block length and the solvent selectivity on the chain exchange rate, we synthesized two series of protonated and deuterated copolymers, one with identical core block length and one with identical corona block length, as well as systematically varied the Flory-Huggins interaction parameter χ by tuning the ratio of the two ionic liquids in the solvent. Notably, the results show that the solvent selectivity has a remarkable effect on the chain exchange rate, and therefore we proposed a more elaborate function of χ for the energy barrier of chain expulsion, which is rationalized by a calculation in the spirit of Flory−Huggins theory. Besides the kinetic study, complementary dynamic light scattering (DLS) and small-angle X-ray scattering (SAXS) experiments were also conducted to investigate the structure of micelles. Particular emphasis was placed on elucidating the scaling relationship between the micelle core radii and the degree of polymerization of the core block in the copolymers.
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    Structure and Dynamics of Block Copolymer Micelles
    (2019-08) Wang, En
    Block copolymers (BCPs) containing two or more distinct chains linked end-to-end will self-assemble into various nanostructures when dissolved in a selective solvent, including spherical and cylindrical micelles, and bilayer vesicles. The equilibrium structure and thermodynamic and dynamic properties are essential factors for processing BCP micelles in various applications. This work is motivated by a desire to investigate structure and chain exchange kinetics of BCP micelles. In this work, nanostructured micelles are formed by poly(styrene)-b-poly(ethylene-alt-propylene) (SEP) diblock, poly(ethylene-alt-propylene)-b-poly(styrene)-b-poly(ethylene-alt-propylene) (EPSEP’), and poly(styrene)-b-poly(ethylene-alt-propylene)-b-poly(styrene) (SEPS’) triblock copolymers in either squalane or binary mixtures of squalane and 1-phenyldodecane, where PEP and PEP’, and PS and PS’, refer to different chain lengths. The solvents are selective to the PEP block, leading to aggregation of PS blocks into the core, and swelling of PEP blocks as the corona. Micelle structures and thermodynamic properties of micelle solutions were characterized by static and dynamic light scattering (SLS and DLS), small-angle X-ray scattering (SAXS) and small-angle neutron scattering (SANS), while the kinetics of chain exchange was investigated by time-resolved small-angle neutron scattering (TR-SANS). These experiments and analyses quantitatively address the effects of corona block length, solvent selectivity, and corona block asymmetry on structure and chain exchange rates in BCP micelles. First, smaller core radii and aggregation numbers, but significantly thicker corona layers were observed in SEP diblock micelles with increasing corona block length. Two orders of magnitude faster kinetics was observed with increasing corona block length by four times. Second, the kinetics of chain exchange kinetics was accelerated by 10 orders of magnitude upon mixing squalane with 50 vol% 1-phenyldodecane for the same SEP block micelle. Third, the aggregation number, core radius, hydrodynamic radius, and critical micelle temperature decreased when varying the corona block asymmetry from asymmetric to symmetric EPSEP’ triblock micelles. The two asymmetric triblocks exhibited one order of magnitude faster exchange rates than the diblock, while the symmetric triblock was two orders of magnitude faster. Another symmetric triblock with two 1.6 times longer corona blocks accelerated the kinetics of chain exchange 10 times more. Finally, micelle ordering were suppressed up to 50 vol% in asymmetric EPSEP’ triblocks, while the equivalent SEP diblock micelles and symmetric EPSEP triblock micelles packed onto body-centered cubic structure at 10 – 30 vol% polymer concentration. These results offer a better understanding of the roles of corona block length, core block–solvent interaction parameter χ, and corona block length asymmetry in structure and chain exchange kinetics, which will ultimately aid in designing optimal block copolymer micelles (i.e., core and corona block length, chain architecture and solvent selectivity) for specific applications.