刘丹,胡海洋,张洁,唐星,陈大为
LIU Dan,HU Hai-yang,ZHANG Jie,TANG Xing,CHEN Da-wei(School of Pharmacy

• 1:沈阳药科大学药学院

摘要(Abstract)：

目的利用聚乙二醇-聚磺胺二甲氧嘧啶(PEG-b-PSD)和PAMAM树状大分子制备具有pH敏感性的复合物胶束并对其制剂学性质进行研究。方法利用正负电荷的相互作用使PEG-b-PSD与PAMAM树状大分子在pH值为7.4条件下形成复合物胶束。考察正负电荷比、离子强度等对zeta电位、载药效果和粒径的影响。利用透射电镜观察制剂形态,考察制剂在不同pH缓冲液和血浆中的释放行为。结果采用正负电荷比为1∶1制备PAMAM/PEG-b-PSD复合物,制剂粒径为50 nm左右,形态为类球形,体外释放速率在pH值为6.5的PBS水溶液中要明显慢于在pH值为7.4的PBS水溶液和血浆中。结论 PEG-b-PSD与PAMAM利用正负电荷相互吸引的方式形成复合物,该复合物具有明显的pH值敏感性,适用于在低pH值部位定位释放药物。
Objective To prepare a noval pH-sensitive poly(amidoamine)(PAMAM) dendrimers using poly(ethylene glycol)-poly(methacryloyl sulfadimethoxine)diblock copolymer(PEG-b-PSD)and PAMAM dendrimers to investigate the properties in vitro. Methods The PSD-b-PEG/PAMAM complex was prepared by electrostatic interaction at PBS 7.4 buffer.The effect of charge ratio(+/-)and ionic strength on zeta potential,drug loading effect and particle size were investigated.The appearance of complex was observed by transmission electron microscope.The drug release in vitro was studied in pH 6.5,pH 7.4 and plasma. Results The PSD-b-PEG/PAMAM complex was prepared at Q(+)∶Q(-)=1∶1,the particle size was around 50 nm,the shape of the complex was spherical.The release rate at pH 6.5 in vitro was faster than that at pH 7.4 and in plasma. Conclusions PEG-b-PSD and PAMAM can be used to prepare PSD-b-PEG/PAMAM complex by electrostatic interaction.The complexes show pH-sensitive properties,and it can be used to deliver drug targetingly to lower pH tissue sites.

关键词(KeyWords)： 聚酰胺-胺(PAMAM)树状大分子;pH敏感;磺胺二甲氧嘧啶;阿霉素
PAMAM dendrimer;pH-sensitive;sulfadimethoxine;doxorubicin

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金资助项目(30873181)

作者(Author): 刘丹,胡海洋,张洁,唐星,陈大为
LIU Dan,HU Hai-yang,ZHANG Jie,TANG Xing,CHEN Da-wei(School of Pharmacy

DOI: 10.14066/j.cnki.cn21-1349/r.2011.02.010

参考文献(References)：

• [1]PATRI A K,ISTVAN J M,JAMES R B,et al.Dendriticpolymer macromolecular carriers for drug delivery[J].Curr Opin Chem Biol,2002,6:466-471.
• [2]BOAS U,HEEGAARD P M H.Dendrimers in drug re-search[J].Chem Soc Rev,2004,3:43-63.
• [3]SONKE S,TOMALIA D A.Dendrimers in biomedicalapplications-reflections on the field[J].Advanced DrugDelivery Reviews,2005,57:2106-2129.
• [4]BHADRA D,BHADRA S,JAIN S,et al.A PEGylateddendritic nanoparticulate carrier of fluorouracil[J].In-ternational Journal of Pharmaceutics,2003,257:111-124.
• [5]SUNG W H,WON HJ.A fluorescence resonance ener-gy transfer probe for sensing pH in aqueous solution[J].Polymer,2008,49:4180-4187.
• [6]AJAY T,YOU HB.Role of a novel multifunctional ex-cipient poly(ethylene glycol)-block-oligo(vinyl sulfad-imethoxine)in controlled release of lysozyme from PL-GA microspheres[J].International Journal of Pharma-ceutics,2008,358:50-59.
• [7]SETHUAMAN V A,BAE Y H.TAT peptide-based mi-celle system for potential active targeting of anti-canceragents to acidic solid tumors[J].Journal of ControlledRelease,2007,118:216-224.
• [8]ROSEITA E,DONALD A T.Poly(amidoamine)(PAM-AM)dendrimers:frombiomimicry to drug delivery andbiomedical applications[J].Drug Discovery Today,2001,6:8-10.
• [9]YUNUS E K,MANOJ K M,SUJATH K,et al.Kan-nana.Drug release characteristics of PAMAM dendrim-er-drug conjugates withdifferent linkers[J].Internation-al Journal of Pharmaceutics,2010,384:189-194.
• [10]YOSHINORI K,KAZUNORI K.Block copolymer mi-celles for delivery of gene and related compounds[J].Advanced Drug Delivery Reviews,2002,54:203-222.
• [11]DURAIRAJ C,RAMAKRISHNA S,FARHAN J A,etal.The development of folate-PAMAM dendrimer con-jugates for targeted delivery of anti-arthritic drugs andtheir pharmacokinetics and biodistribution in arthriticrats[J].Biomaterials,2007,28:504-512.