Solid Lipid Nanoparticles as Drug Delivery System

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1 PROGRESS IN CHEMISTRY Vol. 19 No. 1 Jan., ( ) : O64811 ; R944 : A : X(2007) Solid Lipid Nanoparticles as Drug Delivery System Li Xinwei Sun Lixin Lin Xiaohong Zheng Liqiang 3 ( Key Laboratory of Colloid and Interface Chemistry of Ministry of Education, Shandong University, Jinan , China) Abstract Solid lipid nanoparticle is a new drug delivery system of nano2range. This paper reviews research development of solid lipid nanoparticle as drug carrier, including its components, preparation and surfacial modification, as well as its physico2chemical characteristics, drug incorporation and drug release. Key words solid lipid nanoparticles ; drug delivery system ; drug encapsulation OΠW [1 ] OΠW ;, ; ( solid lipid nanoparticles, SLN) 20 90,, nm,,SLN, : , : e2mail edu. cn

2 88 19 ; 10, ] SLN 1 SL N 111 SLN SLN 3 [11 M ller Gasco, ] M hlen [12 ] [2 Westesen ] SLN SLN SLN Heiata [13 ] [3 ] 1995 (trilaurin, TL) [4,5 SLN ] (azidothymidine, AZT) SLN (AZT2Palmitate,AZT2P) SLN,, DPPC ( dipalmitoylphosphatidy2 lcholine), SLN,,SLN DPPC :DMPG(dimyristoylphosphatidylglycerol) SLN (203 31) nm SLN (294 32) nm 113 SLN SLN SLN SLN DNA SLN ( 1) SLN (nanostructured lipid carrier, NLC) ( lipid drug conjugate nanoparticles, LDC) [6 ] NLC 1 SLN SLN, Fig. 1 Model of SLN NLC, Gasco [14 ] A SLN LDC A 610 % 250nm Mader [7 ] LDC 112 SLN SLN, [ ] [ (dynasan 112) (dynasan 116) ( dynasan 114) [14 ] ( imwitor 900 ) 2 SLN ] [ Fig. 2 Transmission electron micrograph of SLN (dynasan118) ] [ ] [14 ] [7 Mehnert Mgder,SLN

3 1 89 SLN 10nm (250 35) nm Gasco [15 ] SLN 213 XRD(X2ray diffraction) SLN SLN SLN 2 SL N ; ;400W 10min 60, Ahlin [16] SLN 1h,,4 [20 Zeta ] Brij78 SLN : 2 000rpm 8min ; 5 000rpm 10min Dynasan RES : rpm 10min 5ml 25ml 5 000rpm 10min rpm (75 2) 4h 10ml ;, (0 2) 1 000rpm 30ml 2h, SLN m, SLN [3 ] SLN ; [17 ] SLN Hodoshima [21] Souto [9 ] (PEGlipid) (phosphatidylcholine, Ultra2Turrax T25 142O2hexadecanoyl23 2N2salicylidene2 1min (8 000rpm) 500bar 3 ;, [19 ] : Brij78 25ml 6 SLN : 90 5 % PC) DPPC 42O2 2 ( ) ; (THP2ADM) SLN THP2ADM THP2ADM; PEG2lipid,PC DPPC SLN nm SLN (4 1) 60 % Yang [18 ] ; 0124 mol L % nm SLN ( 20,SLN ) 215

4 90 19 SLN SLN SLN OΠW (2 3 ) : Zeta [25 SLN ] 411 Zeta SLN (dynamic light scattering,dls) (photo correlation spectroscopy, PCS) ( ) Ugazio [22 ] A2SLN 3 SL N [25 ],, Zeta, Zeta SLN 412 SLN ( PEG) SLN SLN,,SLN [26 ] [23 ] SLN DSC) X ( small angle X2ray scattering, Garcia2Fuentes [24 ] 2 ( PEG2 stearate) SLN (R) PEG R2PEG SLN,R PEG,DSC 4 SL N, ( differential scanning calorimetry, SAXS) DSC X X SLN X

5 1 91 [31 SLN ] Raman SLN SLN, SLN Lippacher [27 ],SLN [32],,SLN [33 SLN, ] SLN (nuclear magnetic resonance,nmr) (electron spin resonance,esr) SLN H 1 NMR 514 SLN, [28 ] ESR ESR 6 SL N ESR SLN,SLN 3 [29 ] [34 3 ] : (1) ; (2) 2 5 SL N E SLN,, ; (3) 2, SLN SLN 3 SLN : ( ) ; 2 [30 ], ( ) ; 2, ( ) [34 ] 512 Fig. 3 Models of incorporation of active compounds into SLN : SLN homogeneous matrix (left), compound2free core with compound SLN enriched in outer shell (middle), drug2enriched core with lipid shell (right) [34 ],, SLN ; (CA) SLN, CA [35,36 ],CA AUC (area under the concentration2time) SLN MTR(mean residence time) AUC SLN

6 92 19 SLN [ 6 ] M, [ 8 ] M, OΠW [12] Zur M, SLN SLN [37 ] DNA [19] SLN SLN Schubert [38] (BSA) SLN 215 % 10 % nm,Zeta mV - 019mV 7 SLN, SLN [ 1 ] M ller R H, Hildebrand G E ( eds. ). Pharmazeutische Technologie : Moderne Arzneiformen. Stuttgart, Germany : Wissenschaftliche Verlag GmbH, 1998 [ 2 ] Siekmann B, Westesen K. Pharm. Pharmacol. Lett., 1992, [ 3 ] M ller R H, Mehnert W, Lucks J S. Eur. J. Pharm. Biopharm., 1995, 41 : [ 4 ] M ller R H, Mader K, Gohla S. Eur. J. Pharm. Biopharm., 2000, 50 : [ 5 ] Mehnert W, Mgder K. Adv. Drug Deliv. Rev., 2001, 47 : ller R H, Keck C M. J. Biotech., 2004, 113 : [ 7 ] Jores K, Mehnert W, Mgder K, et al. J. Control. Release, 2004, 95 : ller R H, Radtke M, Wissing S A. Int. J. Pharm., 2002, 242 : [ 9 ] Souto E B, Wissing S A, M ller R H, et al. Inter. J. Pharm., 2004, 278 : [10] Lukowski G, Kasbohm J, Wulff H, et al. Inter. J. Pharm., 2000, 196 : [11] Plipps L W. College of Estate Management, 1985, hlen A. PhD Thesis, Free University of Berlin, 1996 [13] Heiata H, Rashad T, Richard R S, et al. Int. J. Pharm., 1997, 146(1) : [14] Ugazio E, Cavalli R, Gasco M R. Inter. J. Pharm., 2002, 241 : [15] Souto E B, Wissing S A, M ller R H, et al. Eur. J. Pharm. Biopharm., 2004, 58 : [16] Ahlin P, Kristl J, Smid2Kobar J. Acta Pharm., 1998, 48 : [17] M ller R H, Radtke M, Wissing S A. Adv. Drug Delivery Rev., 2002, 54(1) : [18] Yang S C, Zhu J B. Drug Dev. Ind. Pharm., 2002, 28 (3) : ( Yin X Y), (Hu F Q), ( Yun H). ( China Medicamentous Industry), 2002, 33 (11) : [20] (Chen D B), (Wang J), (Zhang Q). ( ) (J. Peking Univ. Health Sci. ), 2001, 33(3) : [21] Hodoshima N, Udagawa C, Ando H, et al. Int. J Pharm., 1997, 146(1) : [22] Ugazio E, Cavalli R, Gasco M R. Int. J. Pharm., 2002, 241 (2) : [23] (Wang J), (Zhang Q). Π (Foreign Medical Sci. Sec. Pharmarcy), 1999, 6 : [24] Garcia2Fuentes M, Alonso M J, Torres D J. Colloid Interf. Sci., 2005, 285 : [25] Mehnert W, Mader K. Adv. Drug Delivery Rev., 2001, 47 : [26] Sato K. Crystallization and Polymorphism of Fats and Fatty Acids. New York : Marcel Dekker Inc., [27] Lippacher A, M ller R H, Mader K. Int. J. Pharm., 2000, 196 : [28] Jenning V. PhD Thesis, Free University of Berlin, 1999 [29] Liedtke S, Zimmermann E, Mader K, et al. Proc. Intern. Symp. Control. Rel. Bioact. Mater., 1999, 26 : [30] Zara G P, Cavalli R, Fundaro A, et al. Pharm. Res., 1999, 40 (3) : [31] Yang S, Zhu J, Lu Y, et al. Pharm. Res., 1999, 16 (5) : [32] Dingler A, Blum R P, Niehus H, et al. J. Microencapsulation, 1999, 16(6) : [33] Wissing S A, Muller R H. Pharmazie, 2001, 56(10) : [34] M ller R H, Radtke M, Wissing S A. Adv. Drug. Delivery Rev., 2002, 54 : [35] Ahlin P, Kristl J, Sentjurc M, et al. Int. J. Pharm., 2000, 196 (2) : [36] Jenning V, Gohla S H. J. Microencapsul., 2001, 18(2) : [37] Zur M hlen A, Schwarz C, Mehnert W. Eur. J. Pharm. Biopharm., 1998, 45 : [38] Schubert M A, M ller2goymann C C. Eur. J. Pharm. Biopharm., 2005, 61 : 77 86

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