Preparation And Application Of Native Biomacromolecule Nano- And Micro-Carriers

Carriers can not only protect the activity of drugs, improve the solubility of drugs but also can help the drugs to controlled release, prolong the life time of drug in vivo and achieve target delivery. These will improve the drug efficiency to a large extent. Therefor, carriers were widely developed and applied. In order to attain biodegradable and biocompatible nano-and micro-carriers, native biomacromolecular was perfect materials. This thesis focused on starch microgel which was TEMPO-oxidized and cross-linked by GDGE, and nanoparticles self-assembled by amphiphilic peptides. Firstly, we studyed the controlled uptake and release of lysozyme by microgels and then we prepared different kinds of nanoparticles and evaluated there effects of cytobiology. The following were the main results:(1) We prepared different microgels of different degree of oxidation and cross-link for loading lysozyme. When the degree of oxidation (DO) was 100%, degree of cross-link (RGDGE/polymer (w/w)) was 0.025, the microgel can uptake the most lysozyme and the amount of lysozyme uptaked was 4.87 (g protein/g dry gel). When the pH=7 and ionic strenth was 0.05 M, the amount of lysozyme uptaked reached the maximum. The saturated adsorption amount of lysozyme would increase with the pH increasing, and will decrease with the ionic strenth increasing.(2) The amount of lysozyme released would decrease with the pH increasing. And when pH=3 the amount reached the about 50%. The amount of lysozyme released would increase with the ionic strenth increasing. And when the ionic strenth was 0.5 M the amount reached almost 100%.(3) We prepared 1-2μm long nanotubes,100-200 nm short nanotubes and 30-50 nm nanospheres by self-assembly of amphiphilic peptides. And we improved their stiffness by cross-linking with glutaric dialdehyde.(4) We studyed the cytotoxicity and cell internalization of different nanoparticles with mice breast tumor 4T1 cell line. These nanoparticles behaved low cytotoxicity after co-incubation for 24 h. And different size, shape and stiffness of nanopaticles didn’t have any effect on cytotoxicity. The uptake curve of nanoparticles by 4T1 cells can be finely fitted by Michaelis-Menten equation. The cross-linked nanoparticles had a faster uptake speed than noncross-linked nanoparticles. Further more nanoparticles with smaller size can be uptaken faster and nanosphere also can be uptaken faster than nanotube.