Preparation And Studies Of Starch Nanoparticle As Drug Delivery

Recently, drug delivery systems based on polymeric nanoparicles have attractedmore and more attention, especially the natural polysaccharide carries. Encapsulatingdrugs in or conjugating drugs on particulate carriers can not only prevent drugs fromenzymatic degradation but also prolong the drug’s circulation in the blood stream toimprove the cure efficacy. Starch, as one of the most widespread polysaccharide innature has been extensively employed for biopharmaceutical drug delivery due to itsbiocompatibility and biodegradability.In this thesis, starch-based nanoparticles with predictable size were prepared bysodium hydroxide/urea solution. Furthermore, the biocompatible starch nanoparticlesgraft poly (glutamic acid)(SNP-g-PGA) was synthesized by click reaction. Then therelease behavior of insulin-loaded was studied.Specifically，the results in this dissertation includes as followings:1. The new mix solvent, sodium hydroxide/urea aqueous solution pre-cooled to-10°C, had been developed to disperse corn starch in water below its gelatinizationtemperature. By adjusting the parameter such as sodium hydroxide/urea ratio,temperature and stirring rate, the size of particles could be controlled from micro-tonanometer. This process led to the nanoparticles without changing the chemicalstructure of starch granules but changing the crystallinity pattern of freeze-driedstarch samples from this work.2. Firstly, SNP-g-PBLG was successfully synthesized by click grafting reactionbetween azide-starch nanoparticles (SNP-N3) and alkyne-poly (γ-benzyl-L-glutamate)(alkyne-PBLG). After debenzylation of SNP-g-PBLG by HBr, pH-sensitiveSNP-g-PGA, a delivery for insulin, was obtained. In vitro the release experiment ofinsulin loaded in SNP-g-PGA was carried out. At artificial gastric juice (pH=1.2)loaded-insulin released from the nanoparticles more slowly than that at artificialintestinal liquid (pH=6.8) due to the introduction poly (glutamic acid). These resultsindicated that SNP-g-PGA could protect the insulin against a harmful gastricenvironment and prevent enzymatic degradation, while controlling the drug releaseand increasing their absorption in the intestine.