聚合物胶束口服吸收机制的研究进展Advances on the oral absorption of polymeric micelles
陈东,丁平田,邓意辉
CHEN Dong,DING Ping-tian,DENG Yi-hui (School of Pharmacy
摘要(Abstract):
目的对聚合物胶束作为口服给药载体的研究方法和吸收机制进行综述。方法参考近年来国内外文献共19篇,总结有关聚合物胶束作为口服给药载体的研究,对其中涉及到的口服吸收机制做以分类和总结。结果目前在聚合物的口服吸收常用的研究方法有Caco-2细胞模型、小肠翻转模型和动物模型,共同作为研究聚合物口服吸收机制的手段。聚合物胶束作为药物载体口服的吸收机制分为:a.通过抑制P-糖蛋白增加吸收;b.以胞饮形式吸收;c.经被动扩散;d.与胆汗相关的吸收。结论对聚合物胶束作为口服给药载体的研究方法和吸收机制进行了报道,为聚合物口服研究提供了参考。
Objective To summarize the methods and mechanisms involved in researches about oral polymeric micelles.Methods According to the polymeric micelles with regard to carrier of oral uptake,the oral absorption of polymeric micelles were classified and reviewed on the basis of published literatures.Results Caco-2 cells,reverted rat intestine,and animal model can be used as common models to investigate the absorption mechanism for oral polymeric micelles.With these models,four mechanisms had been introduced to explain the phenomenon related to micelles absorption,i.e.inhibition on P-gp,pinocytosis,simple passive diffusion and the oral uptake with the influence of the bile.Conclusions The methods and mechanisms involved in researches about oral polymeric micelles are reviewed,and this article will provide references for the studies of polymeric micelles for oral administration.
关键词(KeyWords):
聚合物胶束;口服;生物利用度;吸收机制
polymeric micelles;oral administration;bioavailability;absorption mechanism
基金项目(Foundation): 国家重点基础研究发展计划资助项目(2009CB903302)
作者(Author):
陈东,丁平田,邓意辉
CHEN Dong,DING Ping-tian,DENG Yi-hui (School of Pharmacy
DOI: 10.14066/j.cnki.cn21-1349/r.2010.08.012
参考文献(References):
- [1]TORCHILIN V P.Structure and design of polymericsurfactant-based drug delivery systems[J].Journal ofControlled Release,2001,73:137-172.
- [2]FERREC E L,CHESNE C,ARTUSSON P,et al.Invitromodels of the intestinal barrier[J].Alternatives toLaboratory Animals,2001,29(6):649-668.
- [3]MATHOTF,BEIJSTERVELDT L V,PREAT V,et al.Intestinal uptake and biodistribution of novel polymericmicelles after oral administration[J].Journal of Con-trolled Release,2006,111:47-55.
- [4]HASSELTP M,JANSSENS G E P J,SLOT T K,et al.The influence of bile acids on the oral bioavailability ofvitamin K encapsulated in polymeric micelles[J].Jour-nal of Controlled Release,2009,133(2):161-168.
- [5]ZHANG L F,EISENBERG A.Multiple morphologies of“crew-cut”aggregates of polystyrene-b-poly(acrylicacid)bolck copolymers[J].Science,1995,268:1728-1731.
- [6]YOO H S,PARK T G.Biodegradable polymeric mi-celles composed of doxorubicin conjugated PLGA-PEGblock copolymer[J].J Control Release,2001,70:63-70.
- [7]BLANCHETTE J,PEPPAS N A.Oral chemotherapeuticdelivery design and cellular response[J].Annals of Bi-omedical Engineering,2005,33(2):142-149.
- [8]DABHOLKAR R D,SAWANT R M,MONGAYT D A,et al.Polyethylene glycol-phosphatidylethanolamineconjugate(PEG-PE)-based mixed micelles Some prop-erties,loading with paclitaxel,and modulation ofP-gly-coprotein-mediated efflux[J].International Journal ofPharmaceutics,2006,315:148-157.
- [9]MATHOT F,RIEUX A D,ARIEN A,et al.Transportmechanisms of mmePEG750P(CL-co-TMC)polymericmicelles across the intestinal barrier[J].Journal ofControlled Release,2007,124:134-143.
- [10]MATHOTF,SCHANCK A,BAMBEKE F V,et al.Pas-sive diffusion of polymeric surfactants across lipid bi-layers[J].Journal of Controlled Release,2007,120:79-87.
- [11]SEZGIN Z,YUKSEL N,BAYKARA T.Investigation ofpluronic and PEG-PE micelles as carriers of meso-tet-raphenyl porphine for oral administration[J].Interna-tional Journal of Pharmaceutics,2007,332:161-167.
- [12]ZASTRE J,JACKSON J,WONG W,et al.Methoxy-polyethylene glycol-block-polycaprolactone diblock co-polymers reduceP-glycoprotein efflux in the absence ofa membrane fluidization effect while stimulatingP-gly-coprotein ATPase activity[J].Journal of Pharmaceuti-cal sciences,2007,96(4):864-875.
- [13]ZASTRE J,JACKSON J,BAJWA M.Enhanced cellularaccumulation of aP-glycoprotein substrate,rhodamine-123,by caco-2 cells using low molecular weight me-thoxypolyethylene glycol-block-polycaprolactonediblock copolymers[J].European Journal of Pharma-ceutics and Biopharmaceutics,2002,54:299-309.
- [14]YOKOYAMA M,OKANO T,SAKURAI Y,et al.Selec-tive delivery of adiramycin to a solid tumor using a pol-ymeric micelle carrier system[J].JournaI of Drug Tur-gering,1999,7(3):171-186.
- [15]YAMAMOTO Y,NAGASAKI Y,KATO Y.Long-circu-lating poly(ethylene glycol)-poly(Image-lactide)blockcopolymer micelles with modulated surface charge[J].Journal of Controlled Release,2001,77:27-38.
- [16]BATRAKOVA E V,HAN H Y,MILLER D W,et al.Effects of pluronic P85 unimers and micelles on drugpermeability in polarized BBMEC and caco-2 cells[J].Pharmaceutical Research,1998,15(10):1525-1532.
- [17]BROMBERG L.Polymeric micelles in oral chemothera-py[J].Journal of Controlled Release,2008,128:99-112.
- [18]ZASTRE J,JACKSON J,BURTH.Evidence for modu-lation ofP-glycoprotein-mediated efflux by methoxy-polyethylene glycol-block-polycaprolactone amphiphilicdiblock copolymers[J].Pharmaceutical Research,2004,21(8):1489-1497.
- [19]DEMINA T,GROZDOVA I,KRYLOVA O,et al.Rela-tionship between the structure of amphiphilic polymersand their ability to disturb lipid bilayers[J].Biochem-istry,2005,44:4042-4054.