刘凯,孙进,何仲贵
LIU Kai,SUN Jin,HE Zhong-gui(School of Pharmacy

• 1:沈阳药科大学药学院
• 2:沈阳药科大学药学院
• 3:沈阳药科大学药学院 辽宁沈阳110016
• 4:辽宁沈阳110016

摘要(Abstract)：

目的介绍新型的纳米结构脂质载体系统的研究进展,为其研究和应用提供参考。方法查阅相关文献33篇,进行整理和归纳。结果新型的纳米结构脂质载体能够克服固体脂质纳米粒的一些不足,并具有独特的结构特征,药物的包封机理和释放特征。结论纳米结构脂质载体作为药物传递系统的一种新剂型,具有广阔的发展前景。
Objective To review the study on novel nanostructured lipid carriers(NLC) and provide a reference for the further research and development of NLC.Methods The structure features,production methods,stability,drug incorporation and drug release mechanisms,application of NLC were introduced on the basis of related references.Results Novel NLC could overcome the potential drawbacks of solid lipid nanoparticles(SLN) and possess the particular structure features,drug incorporation mechanisms and drug release characters.Conclusions As a new dosage form of drug delivery systems,NLC has an exciting prospect in pharmaceutics.

关键词(KeyWords)： 纳米结构脂质载体;固体脂质纳米粒;结构特征;包封;释放;应用
nanostructured lipid carriers;solid lipid nanoparticles;structure features;incorporation;release;application

Abstract:

Keywords:

基金项目(Foundation):

作者(Author): 刘凯,孙进,何仲贵
LIU Kai,SUN Jin,HE Zhong-gui(School of Pharmacy

参考文献(References)：

• [1]MüLLER R H,LUCKS J S.Arzneistofftrager aus fes-ten Lipidteilchen,Feste Lipidnanospharen(SLN)[P].European Patent.No.EP 0605497:1996-7-13.
• [2]MEHNERT W,MADER K.Solid lipid nanoparticlesProduction,characterization and applications[J].AdvDrug Deliv Rev,2001,47(2-3):165-196.
• [3]MüLLER R H,MADER K,GOHLA S.Solid lipidnanoparticles(SLN)for controlled drug delivery-a re-view of the state of the art[J].Eur J Pharm Bio-pharm,2000,50(1):161-177.
• [4]WISSING SA,KAYSER O,MüLLER R H.Solid lipidnanoparticles for parenteral drug delivery[J].AdvDrug Deliv Rev,2004,56(9):1257-1272.
• [5]MüLLER R H,RADTKE M,WISSING S A.Nanos-tructured lipid matrices for improved microencapsu-lation of drugs[J].Int J Pharm,2002,242(1-2):121-128.
• [6]JENNING V,THUNEMANN A F,GOHLA S H.Characterisation of a novel solid lipid nanoparticle car-rier system based on binary mixtures of liquid and solidlipids[J].Int J Pharm,2000,199(2):167-177.
• [7]JENNING V,GOHLA S H.Encapsulation of retinoidsin solid lipid nanoparticles(SLN)[J].J Microencap-sul,2001,18(2):149-158.
• [8]SOUTO E B,WISSING S A,MüLLER R H.Develop-ment of a controlled release formulation based on SLNand NLC for topical clotrimazole delivery[J].Int JPharm,2004,278(1):71-77.
• [9]HU F Q,JIANG S P,DU Y Z,et al.Praparation andcharacterization of stearic acid nanostructured lipid car-riers by solvent diffusion method in an aqueous system[J].Colloids Surf B:Biointerfaces,2005,45(3-4):167-173.
• [10]MüLLER R H,RADTKE M,WISSING S A.Solidlipid nanoparticles(SLN)and nanostructured lipid car-riers(NLC)in cosmetic and dermatological prepara-tions[J].Adv Drug Deliv Rev,2002,54(Suppl 1):131-155.
• [11]SOUTO EB,WISSING S A,MüLLER R H,et al.E-valuation of the physical stability of SLN and NLC be-fore and after incorporation into hydrogen formulations[J].Eur J Pharm Biopharm,2004,58(1):83-90.
• [12]JENNING V,MADER K,GOHLA S H.Solid lipidnanoparticles based on binary mixtures of liquid andsolid lipid:a 1H NMR study[J].Int J Pharm,2000,205(1-2):15-21.
• [13]GARCIA-FUENTES M,AOLORS M J,TORRES D.Design and characterization of a new drug nanocarriermade from solid-liquid lipid mixtures[J],J ColloidInterface Sci,2005,285(2):590-598.
• [14]JORES K,MEHNERT W,MADER K.Physicochemi-cal investigations on solid lipid nanoparticles and on oil-loaded solid lipid nanoparticles:a nuclear magnetic res-onance and electron spin resonance study[J].PharmRes,2003,20(8):1274-1283.
• [15]JORES K,MEHNERT W,MADER K,et al.Investi-gation on the structure of solid lipid nanoparticles(SLN)and oil-loaded solid lipid nanoparticles byphoton correlatin spectroscopy,field-flow fractiona-tion and transmission electron microscopy[J].J ControlRelease,2004,95(2):217-227.
• [16]JORES K,HABERLAND A,MADER K,et al.Solidlipid nanoparticles(SLN)and oil-loaded SLN studiedby spectrofluorometry and raman spectroscopy[J].Pharm Res,2005,22(11):1887-1897.
• [17]SAUPE A,GORDON K C,RADES T.Structural in-vestigations on nanoemulsions,solid lipid nanoparticlesand nanostructured lipid carriers by cryo-field emis-sion scanning electron microscopy and raman spec-troscopy[J].Int J Pharm,2006,314(1):56-62.
• [18]MüLLER R H,MADER K,LIPPACHER A.Fest-flussig(halbfeste)Lipidpartikel und Verfahren zurHerstellung hochkonzentrierter Lipidpar-tikeldispersionen[P].PCT application PCT/EP00/04565(2000-11-30).
• [19]LI Jun-chan,FANG Xiao-ling,SHA Xian-yi et al.Preparation of 9-nitrocamptothecin semi-solid lipidnanoparticles and pharmacokinetics in rats[J].Chin JPharm,2004,35(10):599-602.
• [20]LI Jun-chan,SHA Xian-yi,ZHANG Li-jun,et al.9-Ni-trocamptothecin nanostructured lipid carrier system:invitro releasing characteristics,uptake by cells,and tis-sue distributionin vivo[J].Acta Pharm Sin,2005,40(11):970-975.
• [21]HU Fu-qiang,JIANG Sai-ping,DU Yong-zhong,et al.Preparation and characteristics of monostearin nanos-tructured lipid carriers[J].Int J Pharm,2006,314(1):83-89.
• [22]RICCI M,PUGLIA C,BONINA F,et al.Evaluationof indomethacin percutaneous absoption from nanos-tructured lipid carriers(NLC):in vitroandin vivostudies[J].J Pharm Sci,2005,94(5):1149-1159.
• [23]UNER M,WISSING S A,MüLLER R H,et al.Solidlipid nanoparticles(SLN)and nanostructrued lipid car-riers(NLC)for application of ascorbyl palmitate[J].Pharmazie,2005,60(8):577-582.
• [24]TEERANACHAIDEEKUL V,MüLLER R H,JUN-YAPRASERT V B.Encapsulation of ascorbyl palmi-tate in nanostructured lipid carriers(NLC)-Effects offormulation parameters on physicochemical stability[J].Int J Pharm,2007,340(1-2):198-206.
• [25]CASTELLI F,PUGLIA C,SARPIETRO M G,et al.Characterization of indomethacin-loaded lipid nanopar-ticles by differential scanning calorimetry[J].Int JPharm,2005,304(1-2):231-238.
• [26]BORGIA S L,REGEHLY M,SCHAFER-KORTINGM,et al.Lipid nanoparticles for skin penetration en-hancement-correlation to drug lacalization within theparticle matrix as determined by fluorescence and par-electric spectroscopy[J].J Control Release,2005,110(1):151-163.
• [27]SOUTO E B,MüLLER R H.SLN and NLC for topi-cal delivery of ketoconazole[J].J Microencapsul,2005,22(5):501-510.
• [28]BRAEM C,BLASCHKE T,KRAMER K D,et al.In-teraction of drug molecules with carrier systems asstudied by parelectric spectroscopy and electron spinresonance[J].J Control Release,2007,119(1):128-135.
• [29]MüLLER R H,LUCK M,KREUTER J.Medicamentexcipient particles for tissue-specific application of amedicament[P].United States Patent,6,288,040:2001-9-11.
• [30]UNER M,WISSING S A,MüLLER R H,et al.Skinmoisturizing effect and skin penetration of ascorbylpalmitate entrapped in solid lipid nanoparticles(SLN)and nanostructured lipid carriers(NLC)incorporatedinto hydrogel[J].Pharmazie,2005,60(10):751-755.
• [31]LIPPACHER A,MüLLER R H,MADER K.Liquidand semisolid SLNTM dispersion for topical applica-tion:rheological characterization[J].Eur J Pharm Bio-pharm,2004,58(3):561-567.
• [32]SOUTO E B,GOHLA S H,MüLLER R H.Rheologyof nanostructured lipid carriers(NLC)suspended in aviscoelastic medium[J].Pharmazie,2005,60(9):671-673.
• [33]TEERANACHAIDEEKUL V,SOUTO E B,MüLLER R H,et al.Cetyl palmitate-based NLC fortopical delivery of Coenzyme Q10-Development,physicochemical characterization and in vitro releasestudies[J].Eur J Pharm Biopharm,2007,67(1):141-148.