Synthesis Of A New Type Of Drug Delivery Material And Preparation Of Nanoparticles

Poly(L-lactic acid)(PLLA),a kind of synthetical aliphatic polyesters,bears nontoxicity, wonderful biologic compatibility and biodegradable properties,which is harmless and non-toxic to the environment.Because of its bright prospects,PLLA has attracted much attention from both industrial and academic fields.Therefore,it has found applications in drug delivery carders,surgical implants and tissue engineering.The feature of hydrophobicity and lack of functional groups for chemical reaction restricts its application.In this paper other monomers was troosed to copolymerizatoin with L-lactic acid for improving these properties.A series of hydroxyl terminated PLLA(PLLA-OH) were synthesized by direct melt copolymerization with stannous chloride and stannous octoate as catalyst activated from L-lactic acid.The optimum polymerization conditions was investigated and then got the best synthetic condition.The dose of SnCl₂·2H₂O and Sn(OCT)₂ reach to 0.1mol%,vacuum of reaction system is improved gradually,polymerization temperature is 180℃,polymerization time is 10 hours.The synthesized PLLA-OH was purified by CH₂Cl₂- CH₃OH.The highest weight-average molecular weight has exceeded 10000.The synthesized PLLA-OH was detected by infrared spectroscopy(IR),proton nuclear magnetic resonance(¹H-NMR) and differential scanning calorimeter(DSC).The main chain of polyphosphate(EDP) bond is easy degradable under the physical conditions,and polyphosphate has a good biocompatibility and high variability of its structure which is conducive to its structure modification and functionalization.Polyethylene glycol(PEG) has a good hydrophilicity and can be degraded in living creature,when its number-average molecular weight belows 4000.Because of properties of EDP and PEG,we synthesized the amphipathic polymer poly(L-lactic acid- polyphosphate- polyethylene glycol) (PLLA/EDP/PEG),by the melt copolymerization with different content of PEG.The structures and properties of final copolymer were characterized by FT-IR,¹H-NMR,³¹p-NMR,DSC and XRD.The influence of raw materials ratio on the copolymer was discussed in detail.Results showed that:the chain of polyphosphate improved the hydrophilicity and biodegradability of the copolymer;PLLA and PEG both show crystallization.The introduction of PEG could improve the hydrophilicity of the copolymer and caused decreased in value of Tg.PEG rich copolymer could lead to an accelerate degradation rate.The PLLA/EDP/PEG nanospheres with size distribution 100nm-200nm were prepared by solvent evaporation method.Their sizes were influenced by PLA chain length and PEG chain length.When the proportion of the PEG was 50mo1%,the highest drug encapsulation efficiency(EE,83.54%) and drug loading content(DLC,19.36%) were got,at the same time drug release rate in vito of PLLA/EDP/PEG nanospheres were promoting to the maxim.We studied PLLA/EDP/PEG nanospheres drug release rate in different pH solutions. Results showed that,PLLA/EDP/PEG nanospheres presented the maxium rate in the alkaline solution...