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Investigation on Acid-labile Biodegradable Polymers with Conjugated Galactose as Drug Carriers

Author: WuGuanNan
Tutor: LiXiaoHong
School: Southwest Jiaotong University
Course: Biomedical Engineering
Keywords: PH -sensitive polymer Microspheres Click Chemistry HCPT Degradation Release
CLC: TQ460.1
Type: Master's thesis
Year: 2009
Downloads: 49
Quote: 3
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Abstract


The tumor site using acidic environment , the use of anticancer drugs pH -sensitive polymer as the carrier material formulations , mainly through the weak acid ( carboxyl group ) or a weak base ( amino ) groups ionized or protonated , etc. to achieve the acidity sensitivity . Liver targeting the drug delivery system can be selectively enriched in the liver lesion, while reducing its toxic effects on normal tissues , in order to improve drug bioavailability . Hydroxycamptothecin (HCPT) having a wide antitumor spectrum, but because it does not dissolve in water and physiologically acceptable organic solvents , and easy to change and a low anti-tumor activity and have serious side effects in the form of carboxylate , limiting HCPT the clinical application . This topic aims to study a new type of acidity galactosyl -containing sensitive polymer and HCPT carrying drug-loaded nanospheres prepared . The pH -sensitive acetal group into polylactic acid - polyethylene glycol copolymer backbone , the use of click chemistry , synthetic means, the galactosyl successfully grafted onto the polymer backbone , to obtain a biodegradable both , acidity sensitivity and target group-containing polymer PGBELA. Fourier transform infrared spectroscopy (FTIR) , and nuclear magnetic resonance (1H-NMR) , etc. verified the target structure of the polymer , gel permeation chromatography (GPC) determined the molecular weight of polymers of 22.3 kDa. Nano- precipitation method carries out Hydroxycamptothecin microspheres , scanning electron microscopy (SEM) observations show that microsphere morphology than regular, more uniform size , average particle size of drug-loaded microspheres were 290 nm, and the particles will active and passive targeting with targeting characteristics. However, the actual drug loading of microspheres and parcel efficiency is relatively low , the conditions need to be further optimized into a ball . Free acidity sensitive groups in the polylactic acid polyethylene glycol copolymer (PELA) as control , was studied microspheres pH7.4, pH6.4 and pH5.6 buffer solution in vitro degradation and drug release . The results showed that the matrix polymer PELA microspheres degradation and drug release in neutral and acidic conditions similar behavior , but PGBELA microspheres under acidic conditions significantly accelerated the degradation in the acidic environment than the neutral environment more quickly the drug release rate , showing the sensitivity characteristics of acidity .

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