溶剂蒸发法制备支化聚合物基疏水药物纳米颗粒
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摘要
文章研究了在有机溶剂(如乙醇)中,通过溶剂蒸发制备疏水性药物纳米颗粒的方法及制备的纳米材料。以具有生物相容性的支化聚(乙二醇)-b-(N-异丙基丙烯酰胺)聚合物纳米为支架,装载不同疏水药物,经过溶剂蒸发,得到稳定的纳米药物,同时能很方便地溶解在水中得到水性药物纳米颗粒分散体。研究表明:疏水性药物纳米颗粒中,酮洛芬药物纳米颗粒(Dh≈200nm),可以在溶液中稳定保存9个月;当药物与聚合物质量比为0.33∶1时产率可达96%,质量比为1∶1时产率可达到80%。采用透射电子显微镜(transmission electron microscope,TEM)、动态光散射仪(dynamic light scattering,DLS)表征了药物纳米的尺度和结构。
Nanoparticles loaded with hydrophobic drugs were prepared by ambient solvent evaporation from ethanol at room temperature.Poly(ethylene glycol)-b-(N-isopropylacrylamide)branched diblock copolymer nanomaterials were employed as the support to facilitating the formation of stable nanoparticles suspended in aqueous media of drug nanoparticles so as to avoid the crystallization.After the initial solvent evaporation,the dry materials obtained exhibited excellent stability during storage and could be readily dissolved in water to produce aqueous drug nanoparticles dispersions.The results showed that among the hydrophobic compounds investigated,Ketoprofen nanoparticles(Dh≈200 nm,stable up to nine months in solution)could be produced with a drug suspension yield of 96% at a drug/polymer ratio of 0.33∶1 or a drug suspension yield of 80%at a drug/polymer ratio of 1∶1 respectively.Transmission electron microscope(TEM)and dynamic light scattering(DLS)were applied to characterizing the size and structure of the drug nanoparticles.
Nanoparticles loaded with hydrophobic drugs were prepared by ambient solvent evaporation from ethanol at room temperature.Poly(ethylene glycol)-b-(N-isopropylacrylamide)branched diblock copolymer nanomaterials were employed as the support to facilitating the formation of stable nanoparticles suspended in aqueous media of drug nanoparticles so as to avoid the crystallization.After the initial solvent evaporation,the dry materials obtained exhibited excellent stability during storage and could be readily dissolved in water to produce aqueous drug nanoparticles dispersions.The results showed that among the hydrophobic compounds investigated,Ketoprofen nanoparticles(Dh≈200 nm,stable up to nine months in solution)could be produced with a drug suspension yield of 96% at a drug/polymer ratio of 0.33∶1 or a drug suspension yield of 80%at a drug/polymer ratio of 1∶1 respectively.Transmission electron microscope(TEM)and dynamic light scattering(DLS)were applied to characterizing the size and structure of the drug nanoparticles.
引文
[1] BARVE A,CHEN C,HEBBAR V,et al.oral bioavailability and pharmacokinetics of chemopreventive kaempferol in rats[J].Biopharm Drug Dispos,2009,30(7):356-365.
[2] SERAJUDDIN A T M.Salt formation to improve drug solubility[J].Adv Drug Del Rev,2007,59(7):603-616.
[3]李战,吴敏.纳米技术和纳米中药的研究进展[J].上海中医药杂志,2003,37(1):61-64.
[4]平其能.纳米药物和纳米载体系统[J].中国新药杂志,2002,11(1):42-46.
[5] JUNYAPRASERT V B,MORAKUL B.Nanocrystals for enhancement of oral bioavailability of poorly water-soluble drugs[J].Asian Journal of Pharmaceutical Sciences,2015,10(1):13-23.
[6] CANELAS D A,HERLIHY K P,DESIMONE J M.Topdown particle fabrication:control of size and shape for diagnostic imaging and drug delivery[J].Wiley Interdiscip Rev Nanomed Nanobiotechnol,2009,1(4):391-404.
[7] SINHA B,MULLER R H,MOSCHWITZER J P.Bottomup approaches for preparing drug nanocrystals:formulations and factors affecting particle size[J].International Journal of Pharmaceutics,2013,453(1):126-141.
[8]王廉卿,戎欣玉,刘魁,等.纳米药物晶体的制备技术及其应用[J].河北科技大学学报,2014,35(4):339-348.
[9] ChAN H K,KWOK P C L.Production methods for nanodrug particles using the bottom-up approach[J].Advanced Drug Delivery Reviews,2011,63(6):406-416.
[10] KONNO H,TAYLOR L S.Influence of different polymers on the crystallization tendency of molecularly dispersed amorphous felodipine[J].J Pharm Sci,2006,95(12):2692-2705.
[11]龙丽霞,原续波,钱小敏,等.聚乳酸/双亲性葡聚糖中空纳米囊泡包载亲水性药物及释放[J].天津大学学报(自然科学与工程技术版),2013,46(6):510-515.
[12] WAIS U,JACKSON A W,ZUO Y M,et al.Drug nanoparticles by emulsion-freeze-drying via the employment of branched block copolymer nanoparticles[J].J Control Release,2016,222:141-150.
[13] HANCOCK B C,PARKS M.What is the true solubility advantage for amorphous pharmaceuticals?[J].Pharm Res,2000,17(4):397-404.
[2] SERAJUDDIN A T M.Salt formation to improve drug solubility[J].Adv Drug Del Rev,2007,59(7):603-616.
[3]李战,吴敏.纳米技术和纳米中药的研究进展[J].上海中医药杂志,2003,37(1):61-64.
[4]平其能.纳米药物和纳米载体系统[J].中国新药杂志,2002,11(1):42-46.
[5] JUNYAPRASERT V B,MORAKUL B.Nanocrystals for enhancement of oral bioavailability of poorly water-soluble drugs[J].Asian Journal of Pharmaceutical Sciences,2015,10(1):13-23.
[6] CANELAS D A,HERLIHY K P,DESIMONE J M.Topdown particle fabrication:control of size and shape for diagnostic imaging and drug delivery[J].Wiley Interdiscip Rev Nanomed Nanobiotechnol,2009,1(4):391-404.
[7] SINHA B,MULLER R H,MOSCHWITZER J P.Bottomup approaches for preparing drug nanocrystals:formulations and factors affecting particle size[J].International Journal of Pharmaceutics,2013,453(1):126-141.
[8]王廉卿,戎欣玉,刘魁,等.纳米药物晶体的制备技术及其应用[J].河北科技大学学报,2014,35(4):339-348.
[9] ChAN H K,KWOK P C L.Production methods for nanodrug particles using the bottom-up approach[J].Advanced Drug Delivery Reviews,2011,63(6):406-416.
[10] KONNO H,TAYLOR L S.Influence of different polymers on the crystallization tendency of molecularly dispersed amorphous felodipine[J].J Pharm Sci,2006,95(12):2692-2705.
[11]龙丽霞,原续波,钱小敏,等.聚乳酸/双亲性葡聚糖中空纳米囊泡包载亲水性药物及释放[J].天津大学学报(自然科学与工程技术版),2013,46(6):510-515.
[12] WAIS U,JACKSON A W,ZUO Y M,et al.Drug nanoparticles by emulsion-freeze-drying via the employment of branched block copolymer nanoparticles[J].J Control Release,2016,222:141-150.
[13] HANCOCK B C,PARKS M.What is the true solubility advantage for amorphous pharmaceuticals?[J].Pharm Res,2000,17(4):397-404.