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Synthesis and Characterization of Environment-Responsiveness Micelles and Polyanionic Nano-Micelles Constituted of Modified Poly (Aspartic Acid)s Derivatives
Dissertation

Synthesis and Characterization of Environment-Responsiveness Micelles and Polyanionic Nano-Micelles Constituted of Modified Poly (Aspartic Acid)s Derivatives

Hsu, Shih-Pin
Doctor of Philosophy (PHD), 國立清華大學, 化學工程學系
2011

Abstract

環境應答 奈米高分子材料 低溫臨界溶液性質 polymersomes 聚天門冬氨酸 聚陰離子 Environmental response nano polymer LCST polymersome poly(aspartic acid) polyanionic
Polymers modified with specific segments equipped polymers with environmental-response ability that have been studied extensively in biomedical fields. Furthermore, the nanotechnology is associated with the development of next- generation industry in the 21st century including pharmaceutical industry. In this paper, two topics are included, (1) Thermo- and pH- responsive Polymersomes of Poly (α, β-N-substituted-DL-aspartamide)s and (2) Design of polyanionic nanocarriers based on modified poly (aspartic acid)s for oral administration: synthesis and characterization. The related papers about environment-responsive and/or nano-polymeric materials which have potentials for applying in medicine that have being published in each journal are also categorized and introduced in this paper. The purpose of this research is to find novel materials for medicine and study the relationship between structure and property comprehensively. In this study, a series of novel polymers, poly (α, β-N-substituted-DL- aspartamide)s were successfully synthesized and characterized. The poly (α, β-N-substituted-DL-aspartamide)s showed pH and temperature responsiveness and had phase transitions at different pHs and temperatures. Different ratios of these two amino alcohols were used to modify the polymer to produce a series of copolymers with lower critical solution temperatures (LCSTs) ranging from 53°C to 28℃ when dispersed in aqueous media. Moreover, the LCSTs of the polymers decreased as the pH decreased below neutral. The morphology of the particles formed by these amphiphilic polymers was observed using SEM and TEM, and the particles were found to be polymersomes with shell and hollow core structures and diameters of 0.5–1 um. Another series of partially esterified poly (aspartic acid)s was produced to afford an amphiphilic polyanion, poly (sodium aspartate-g-hexadecyl aspartate) (Na-PASP-g- C16-PASP). The synthesized polyanion could be self-assembled into the nano-scaled micelles and be independent of pH in phosphoric buffer solutions. The polyanionic property can prevent the micelles from being congregated and hindered by mucin as well as facilitate the micelles passing through the mucus of the small intestine. The stability of size transition at different pH levels, from strong acid to alkaline, proved that the micelles could stably transport from the stomach to intestinal lumen prior to arriving in the epithelium of the small intestine. The characteristics of amphiphilic and self-assembled nanomicelles can be utilized to encapsulate the hydrophilic, hydrophobic and even amphiphilic drugs. Furthermore, the nano-dimension (under 100 nm) can be promised to enhance the absorption of the small intestine to improve bioavailability.

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