Study On Degradable Polyurethane As A Drug Delivery Systems

Despite anti-cancer drugs play an important role in cancer therapy, they are usuallycharacterized with significant drawbacks such as toxic and side effect and short half-life.Meanwhile Chitosan and its derivatives pose excellent antibiotic property,bio-compatibility and so on. On the account of recent study on the polyurethane carrier asdrug delivery systems, chitosan has been chosen to modify polyurethane, and then suchpolyurethane has been applied to coat5-fluorouracil(5-fu). Such progress in the respect ofsustained releasing property has been made. The main research content and study methodin this thesis included:(1) The block polymer PLA-PEG-PLA (PGLA) was synthesized with lactide(LA)and polyethylene glycol(PEG) firstly. Secondly, PGLA, isophorone diisocyanate(IPDI),2,2-dimethylolbutanoic acid(DMPA) and carboxymethyl chitosan(CMC) were applied tosynthesis carboxymethyl chitosan modified polyurethane(Ch-PGLAU). Then severalfactors on the product have been discussed such as m(PGLA)/m(IPDI), m(chainextender)/m(PGLA)、 prepolymer reaction time and temperature, m(CMC)/m(chainextender). And the optimum synthesis condition had been determined. Various instruments,such as infrared spectrometric analyzer, differential thermal analyzer, scanning electronmicroscopy, were utilized to characterize different samples. And the factors werediscussed in process of synthesis. The swelling property and degradability were tested andstudied.(2) Ch-PGLAU as carrier were utilized to coat5-fu as a model drug. Severalparameters effecting on the drug loading efficiency and encapsulating efficiency werediscussed, such as5-fu concentration, stirring rate, the variation of different types ofCh-PGLAU. Orthogonal test was applied to determine the optimum preparation condition.The accumulative release rates were tested in phosphate buffer solution(PBS) withdifferent pH value to study drug releasing property from such composite. The releasingresults were fit with different mathematic model to discuss the law of drug release.The research result showed： (1) The optimum prepolymerization conditions were prepolymerization temperature85℃, prepolymerization time4.5h, m(PGLA)/m(IPDI)16%, and m(CMC)/m(chainextender) less than15%. Crystallizations process of PEG segment and PLA segment wererestricted by the other segment. With the molecular weight and content of PEG increasing,the swelling property and degradability appeared declining. In the range of chitosancontent designed, the addition had a little effect on both swelling property anddegradability.(2) The optimum coating conditions were stirring rate700rpm, the initial content of5-fu40mg/mL. With the help of accumulative release rates of5-fu/Ch-PGLAU in vitro, itwas found that alkaline condition would promote such releasing, however notsignificantly. Fitting result revealed that releasing profiles were matched well with theambiexponent equations.