摘要
背景:高分子纳米胶束是近几年正在发展的一类新型药物载体,其载药范围广、结构稳定、具有优良的组织渗透性,体内滞留时间长,能使药物有效地到达靶点。而使其带有智能靶向性以及减弱其初期爆发释放行为成为了最近研究的热点。目的:得到一种低临界溶液浓度在40℃左右的智能靶向药物载体,可以通过对温度的改变而改变其药物释放行为,并进一步通过核交联改善胶束的稳定性以及其药物释放行为。方法:通过N-异丙基丙烯酰胺(NIPAAm)和N,N-二甲基丙烯酰胺(DMAAm)的自由基共聚,合成端羟基聚(N-异丙基丙烯酰胺-co-N,N-二甲基丙烯酰胺)(P(NIPAAm-co-DMAAm))。通过调节巯基乙醇和单体的比例,以及NIPAAm和DMAAm的比例,调节P(NIPAAm-co-DMAAm)的相对分子质量和低临界溶液温度。然后在异辛酸亚锡的催化下,利用P(NIPAAm-co-DMAAm)端羟基引发己内酯开环聚合,得到端羟基P(NIPAAm-co-DMAAm)-b-PCL两亲性嵌段共聚物。该嵌段共聚物再与丙烯酰氯反应得到末端带有不饱和双键的两亲性嵌段共聚物。用透析法制备具有不同核交联程度的纳米载药胶束,并对其释放行为进行研究。结果与结论:得到了温敏段相对分子质量为3600、PCL段相对分子质量为1600的两亲性嵌段共聚物,其低临界溶液浓度为42℃。采用不同比例端羟基和端羧基P(NIPAAm-co-DMAAm)-b-PCL混合,制备得到具有不同核交联程度的温敏性纳米载药胶束。胶束的药物释放速度在43℃快于37℃,随着核交联程度的增高,紫杉醇的释放速度变慢。结果提示以低临界溶液浓度在40℃左右的温敏性P(NIPAAm-co-DMAAm)-b-PCL所制备的胶束,具有一定的温敏控制释放行为,药物释放速度可进一步通过核交联程度来控制。
BACKGROUND：Polymer micelles is a new type of drug carriers developed in recent years,with a wide range of carrying drugs,structural stability,excellent tissue permeability,long residence of drugs in vivo,and effective reaching the target.The performances of intelligent targeting and decreasing the initial burst release have become the focus of recent researches.OBJECTIVE：To obtain an intelligent targeting drug carrier of low critical solution temperature（LCST）at 40℃,to change drug release behavior through the changes of temperature,and to further improve the stability and drug release behavior of the micelles by core-crosslinking.METHODS：By radical polymerization of N-isopropylacrylamide（NIPAAm）and N,N-dimethylacrylamide（DMAAm）,hydroxyl terminated poly（N-isopropylacrylamide-co-N,N-dimethyl acrylamide）[P（NIPAAm-co-DMAAm）]was synthesized.Molecular weight and LCST of P（NIPAAm-co-DMAAm）were regulated by adjusting the mercaptoethanol and monomer ratio,as well as the ratio of NIPAAm and DMAAm.Amphiphilic block copolymer P（NIPAAm-co-DMAAm）-b-PCL was prepared via bulk ring-opening polymerization ofε-caprolactone by using the end hydroxyl group of P（NIPAAm-co-DMAAm）as initiator and stannous octoate as catalyst.The block copolymer reacted with acryloyl chloride to obtain amphiphilic block copolymers with unsaturated double bonds at the terminal.Drug loaded nano-micelles with different nuclear cross-linked degrees were prepared by dialysis method,and its release behavior was investigated.RESULTS AND CONCLUSION：Amphiphilic block copolymers,with the LCST of 42℃,were obtained with hydroxyl or acryloyl endgroup.By blending them at different ratios,thermo-sensitive drug-loaded nano-micelles with different core-crosslinking degrees were prepared.The drug release rate was faster at 43℃ than at 37℃.With the core-crosslinking degrees increasing,the release of paclitaxel gradually slowed.The results suggest that the drug release rate from micelles prepared from thermo-sensitive P（NIP
出处
《中国组织工程研究与临床康复》
CAS
CSCD
北大核心
2010年第29期5505-5510,共6页
Journal of Clinical Rehabilitative Tissue Engineering Research
