Preparation And Characterization Of Magnetic Targeting Drug Microspheres

Magnetic targeted drugs delivery system consists of polymer carrier,drug and magnetic nanoparticles.It could be selectively localized to the target-site of tumor by external magnetic field and then the drug would be delivered to pathological position, thus have the characteristics of high performance,quick result and low poison. Anti-cancer medicine usually while killing cancer cell,more or less injures normal cell,but adopting MTDS can availably overcome this weakness.So it provided a kind of new path to targeted anti-cancer medicine.The aim of this thesis is the synthesis of the magnetic targeted drug microspheres by the suspension cross-linking technique based on biocompatible and biodegradable natural biopolymer chitosan,anti-cancer drug 5-fluorouracil(5-Fu)and magnetic nanoparticles(Fe₃O₄).The interrelationships are studied between phy-chemical preparation parameters and technical indexes of microspheres.It is studied that the kinetic release model of 5-Fu from chitosan microspheres,and influential factors to microspheres localized sites by external magnetic field.Some achieved progresses have been obtained as follows:(1)The magnetic chitosan microspheres were prepared through inverse suspension cross-linking.An orthogonal experimental design and statistical analysis methods were employed to indicate the sequence of the six factors of influence to experiment result was below:Stirring rate＞CTS concentration＞Emulsifier concentration＞Fe₃O₄ concentration＞Cross-linker concentration,Oil/Water.The optimal manufacturing conditions were determined as follows:the concentration of CTS was 0.1%,the concentration of Fe₃O₄ was 0.4%,the concentration of Cross-linker was 1%,oil/water was 20/0.5,the concentration of emulsifier was 20%, and Stirring rate was 3200 r/min.It was a well spherical form with a mean diameter 1.34μm and span 2.35,among which about 77.71%of microspheres were distributed within 0.5 to 5μm size ranges.The saturation magnetization of 5-Fu-MCMs was about 28.06 emu/g.(2)Magnetic chitosan microspheres containing 5-Fu(5-Fu-MCMs) were prepared through inverse suspension cross-linking technique.It was found that the other two factors(CTS concentration,5-Fu concentration)had significantly influence to mean diameter,drug loading and loading efficiency(Sig.＜0.05),except cross-linker concentration through the orthogonal experimental design and statistical analysis methods.The optimal manufacturing conditions were determined as follows: the concentration of CTS was 1.0%,m5-Fu/mCTS ratio was 1/4,and the concentration of Cross-linker was 5%.It was a well spherical form with a mean diameter 3.88μm and span 5.04,among which about 84.73%of microspheres were distributed within 1 to 7μm size ranges.The saturation magnetization of MCMs was about 3.79 emu/g,and microspheres possessed prominent release effect.(3)The in vitro 5-Fu release studies from the microspheres were performed in 7.4 pH phosphate buffer solution.The 5-Fu release from 5-Fu-MCMs followed a biphasic pattern character by an initial rapid release phase,or burst effect within 0.5h, and then a slowly sustained release phase.The drug release obeyed First-order model equation and its 95%determination coefficient R² in all equations was above 0.95.(4)Based on simulation of fluid environment of the blood using a silicone tube flowing system,it was observed that the effect of magnetic microspheres attracted by the magnetic field under different conditions.Methods:By a self-made apparatus of magnetic localization experiment in vitro the accumulation and localization of the magnetic microspheres were determined in different flow velocity and tube diameter. Results:The faster flow velocity the worse accumulation and localization was seen. The magnetic microsphere could be accumulated in a great measure when the flow velocity＜0.05 cm/s,but it almost would be not accumulated when the flow velocity＞5.00 cm/s.In addition,when flow velocity is faster,the relation of accumulation percentage of microspheres and tube diameter isn't too obvious,but when the flow velocity was as low as a certain degree,the relation of the accumulation percentage of microspheres and tube diameter is to present negative correlativity.