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mPEG-P(Ala)-P(Asp)可注射溫度敏感型胺基酸水膠性質探討及其於藥物投遞上的應用
Thesis

mPEG-P(Ala)-P(Asp)可注射溫度敏感型胺基酸水膠性質探討及其於藥物投遞上的應用

鄭傑
Masters, 國立清華大學, 化學工程學系
2015

Abstract

胺基酸水膠 溫度敏感性 藥物投遞 polypeptide hydrogel thermosensitive drug delivery
The Objective of this study was to discuss the thermoresponsive polypeptide hydrogel properties and the potential of hydrogel in drug delivery. methoxy-poly(ethylene glycol)-poly(L-alanine) (mPEG-P(Ala)) is a well-known thermoresponsive polypeptide hydrogel. By using mPEG-NH2 and N-carboxy anhydride-alanine (NCA-alanine) through ring-opening polymerization. Afterwards, using N-carboxyl anhydride β-benzyl L-Aspartate through ring-opening polymerization and removal of the benzyl protecting groups to form the hydrogel. The experimental results indicated that the polypeptide polymer with hydrophilic and hydrophobic parts can form a micelle structure in water. The critical micelle concentration (CMC) was ranged from 0.65 to 0.11 wt%. Zeta potential and particle size measurements of micelle indicated that the number of different mole L-aspartic acid were conjugated to mPEG-P(Ala), the Zeta potential decreased from 20 mV to -20 mV and particle size is about 100-250 nm. TEM and Zeta potential observations indicated that the morphology of micelle affected by Zeta potential. SEM results showed that hydrogel can form three-dimensional network structure. Rheology results showed that viscoelastic properties of the polypeptide hydrogel varied with temperature, indicative of the formation of a gel. MTT assay studies suggested acceptable biocompatibility of the hydrogel and the degradation of hydrogel was accelerated in presence of enzyme. The results of cisplatin encapsulated in hydrogel indicated that the continuous drug release can be controlled by the number of different mole L-aspartic acid were conjugated. From the above results, mPEG-P(Ala) -P(Asp) is a good drug controlled release carriers. It has In-Situ gelling, biocompatibility and biodegradability properties. For the local application of drugs has a considerable advantage.

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