Solid Lipid Nanoparticles (SLN’S) – Trends and Implications in Drug Targeting
Keywords:
Colloidal Drug Carriers, Nanoparticles, Drug Targeting, BiodistributionAbstract
The era of nanotechnology has revolutionized the drug delivery system and persuades new research strategies to flourish. Solid lipid nanoparticles (SLN) has attracted various research groups and companies since the early 1990s, however research in the SLNs is still in its infancy. ‘SLN technology based therapy’ made available a novel and sound platform for therapeutics. Solid lipid nanoparticles have been developed as an important strategy to deliver drugs. These lipid nanoparticles modify drug release, body distribution and kinetics of associated drugs. Other applications of SLNs are tissue/cell targeting of drugs and reduction of unwanted side effects by controlled release. This paper reviews the production techniques, ingredients employed and various applications, also having consideration on various aspects and benefits of solid lipid nanoparticles as colloidal drug carriers.
References
Lakkireddy JS, Adhikari BSR, Dwarkanath ,et
al, Tumoricidal effects of etoposide
incorporated into solid lipid nanoparticles
after intraperitoneal administration in Daltons
lymphoma bearing mice. The AAPS journal
; 8(2)article 29
Maiaa CS, Mehnertb W, Schallerc M,
Kortingc HC, Gyslera A, Haberlanda A,
Schafer-kortinga M. Drug targeting by solid
lipid nanoparticles for dermal use. Journal of
Drug Targeting, 2002; 10:489–495.
Domb AJ. 1993; U.S. Patent, 5188837
Schwarz C, Mehnert W, Lucks JS, Muller RH.
Solid lipid nanoparticles for controlled drug
delivery, J Control Rel. 1994; 30:83-96.
Kante B, Couvreur P, Dubois-Krack G, De
Meester C, Guiot P, Roland M, Speiser P. J.
Pharm. Sci. 1982; 71: 786-791.
Jenning V, Lippacher A, Gohla SH. Medium
scale production of solid lipid nanoparticles
(SLN) by high pressure homogenization. J.
Microencapsul. 2002; 19:1-10.
Lee KE, Cho SH, Lee HB, Jeong SY, Yuk
SH. Microencapsulation of lipid nanoparticles
containing lipophilic drug. J. Microencapsul.
; 20:489–496.
Muller RH, Mehnert W, Lucks JJ, Schwartz
C, Zur Muhlen, A, Weyhers H, Freitas C,
Ruhl D. Eur. J. Pharm. Biopharm. 1995; 41:
Siekmann B, Westesen, K. Melt-homogenized
solid lipid nanoparticles stabilized by the
nonionic surfactant tyloxapol - I. Preparation
and particle size determination. Pharmacol.
Lett. 1994; 3:194–197.
Carsten O, Oliver K, Muller RH. Enzymatic
degradation of dynasan 114 SLN – effect of
surfactants and particle size. Journal of
Nanoparticle Research, 2002; 4: 121–129.
Freitas C, Muller RH. Correlation between
long-term stability of solid lipid nanoparticles
(SLN) and crystallinity of the lipid phase. Eur.
J. Pharm. Biopharm. 1999; 47:125–132.
Zur Muhlen A, Schwarz C, Mehnert W. Solid
lipid nanoparticles (SLN) for controlled drug
delivery - Drug release and release mechanism
Eur. J. Pharm. Biopharm. 1998; 45:149–155.
Reddy LH, Murthy RSR. Etoposide-loaded
nanoparticles made from glyceride lipids:
Formulation, characterization, in vitro drug
release, and stability evaluation.
AAPSPharmSciTech. 005; 6: E158-E166.
Siekmann B, Westesen K. Submicron-sized
parenteral carrier systems based on solid
lipids. Pharmacol. Lett. I. 1992; 123-126.
Mehnert W, Mader K. Solid lipid
nanoparticles: Production, characterization,
applications. Adv. Drug Del. Rev. 2001;
:165-196.
Jenning V, Lippacher A, Gohla SH. Medium
scale production of solid lipid nanoparticles
(SLN) by high pressure homogenization. J.
Microencapsul. 2002, 19: 1-10.
Bekerman T, Golenser J, Domb A.
Cyclosporin nanopartculate lipospheres for
oral administration. J. Pharm. Sci. 2005,
:12-127
Freitas C, Muller RH. Stability determination
of solid lipid nanoparticles SLN® in aqueous
dispersions after addition of the electrolyte. J.
Microencapsul. 1999; 16: 59-71.
Joresa K, Mehnerta W, Drechslerb M, Bunjesc
H,
Johannd C, Madere K. Investigations on the
structure of solid lipid nanoparticles (SLN)
and oil-loaded solid lipid nanoparticles by
photon correlation spectroscopy, field-flow
fractionation and transmission electron
microscopy. J. Control. Rel. 2004; 95: 217-
Schoè N, Zimmermann E, Katzfey U, Hahn H,
Muèller RH, Liesenfeld O. Effect of solid
lipid nanoparticles (SLN) on cytokine
production and the viability of murine
peritoneal macrophages. J. Microencapsul.
; 17: 639- 650.
Wang Y, Wu W. In situ evading of phagocytic
uptake of stealth solid lipid nanoparticles.
Drug Delivery, 2006; 13: 189-192.
Jun H, Shi-wen Z. New research on
development of solid lipid nanoparticles
Journal of Medical Colleges of PLA, 2007;
:385-390.
Wissing SA, Muller RH. Cosmetic
applications of solid lipid nanoparticles (SLN)
Int. J Pharm. 2003; 254:65-68.
Westesen K, Siekmann B, Koch MHJ.
Investigations on the physical state of lipid
nanoparticles by synchrotron radiation X-ray
diffraction, Int. J. Pharm. 1993; 93:189-199.
Goppert TM, Muller RH. Protein adsorption
patterns on poloxamer and poloxaminestabilized solid lipid nanoparticles (SLN). Eur.
J Pharm. Biopharm. 2005; 60: 361–372.
Zara GP, Cavalli R, Bargoni A, Fundaro A,
Vighetto D, Gasco MR. Intravenous
administration to rabbits of non-stealth and
stealth doxorubicin-loaded solid lipid
nanoparticles at increasing concentrations of
stealth agent: Pharmacokinetics and
distribution of doxorubicin in brain and other
tissues. Journal of Drug Targeting, 2002; 10:
–335.
Muller RH, Lucks JS. Arzneistofftraèger aus
festen Lipidteilchen, Feste Lipidnanosphaeren
(SLN). 1996, EP0605497.
Muller RH, Schwarz C, Mehnert W, Lucks JS.
Production of solid lipid nanoparticles (SLN)
for controlled drug delivery. Proc. Int. Symp.
Control. Release Bioact. Mater. 1993; 20:
-481.
Bummer PM. Physical chemical
considerations of lipid-based oral drug
delivery-solid lipid nanoparticles. Review,
Crit. Rev. Ther. Drug. Carrier. Syst. 2004; 21:
-20.
Gasco, MR. 1997. Solid lipid nanospheres
from warm micro-emulsions. Pharm. Tech.
Eur. 9, 52–58.
Zhinan Mei, Huabing Chen, Ting Weng,
Yajiang Yang, Xiangliang Yang. Solid lipid
nanoparticle and microemulsion for topical
delivery of triptolide Eur. J. Pharm. Biopharm.
; 56:189–196.
Serpea L, Catalanob MG, Cavallic R, Ugazioc
E, Boscob O, Canaparoa R, Muntonia E,
Frairiab R, Gascoc MR, Eandia M, Zara GP.
Cytotoxicity of anticancer drugs incorporated
in solid lipid nanoparticles on HT-29
colorectal cancer cell line. Eur. J Pharm.
Biopharm. 2004; 58:673–680.
Joresa K, Mehnerta W, Drechslerb M, Bunjesc
H,
Johannd C, Madere K. Investigations on the
structure of solid lipid nanoparticles (SLN)
and oil-loaded solid lipid nanoparticles by
photon correlation spectroscopy, field-flow
fractionation and transmission electron
microscopy. J. Control. Rel. 2004; 95:217-
Cavalli R, Caputo O, Marengo E, Pattarino F,
Gasco MR. The effects of components of
microemulsions on both size and crystalline
strucure of solid lipid nanoparticles (SLN)
containing a series of model molecules.
Pharmazie, 1998; 53: 392-396.
R.H. Mueller Solid lipid nanoparticles (SLN)
for controlled drug delivery - a review of the
state of the art. Eur. J. Pharm. Biopharm.
; 50:161-177.
Trotta M, Debernardi F, Caputo O.
Preparation of solid lipid nanoparticles by a
solvent emulsification-diffusion technique.
Int. J. Pharm. 2003; 257:153-60.
Heurtault B, Saulnier P, Pech B, Proust JE,
Benoit JP. Physico-chemical stability of
colloidal lipid particles. Biomaterials, 2003;
: 4283–4300.
Souto EB, Muller RH. Investigation of the
factors influencing the incorporation of
clotrimazole in SLN and NLC prepared by hot
high-pressure homogenization. J.
microencapsulation. 2006; 23:377-388.
Bunjes H, Westesen K, Koch MHJ.
Crystallization tendency and polymorphic
transitions in triglyceride nanoparticles. Int. J.
Pharm. 1996; 129:159–75.
Ahlin P, Kristl J, Smid-Kobar J. Optimization
of procedure parameters and physical stability
of solid lipid nanoparticles in dispersions.
Acta Pharm. 1998; 48: 257–267.
Siekmann B, Westesen K. Melt-homogenized
solid lipid nanoparticles stabilized by the
nonionic surfactant tyloxapol- I. Preparation
and particle size determination. Pharmacol.
Lett. 1994; 3:194–197.
Lippacher A, Muller RH, Mader K. Semisolid
SLN dispersions for topical application:
influence of formulation and production
parameters on viscoelastic properties on
viscoelastic properties. Eur. J. Pharm.
Biopharm. 2002; 53:155-160.
Potluri P, Betageri GV. Mixed-micellar
proliposomal systems for enhanced oral
delivery of progesterone. Drug Delivery,
; 13:227–232.
Seeballuck F, Lawless E, Ashford MB,
O’Driscoll CM. Stimulation of triglyceriderich lipoprotein secretion by polysorbate 80:
in vitro and in vivo correlation using caco-2
cells and a cannulated rat intestinal lymphatic
model. Pharm. Res. 2004; 21:2320–2326.
Luo Y, Chen D, Ren L, Zhao X, Qin J. Solid
lipid nanoparticles for enhancing vinpocetine's
oral bioavailability. J. Control. Rel. 2006;
: 53-59.
Venkatesan N, Uchino K, Amagase K, Ito Y,
Shibata N, Takada K. Gastrointestinal patch
system for the delivery of erythropoietin. J.
Control. Rel. 2006; 111:19–26.
Holm R, Mullertz A, Christensen E, Hoy CE,
Kristensen, HG. Comparison of total oral
bioavailability and the lymphatic transport of
halofantrine from three different unsaturated
triglycerides in lymph cannulated conscious
rats. Eur. J. Pharm. Sci. 2001; 14: 331–337.
Driscoll, CMO. Lipid-based formulations for
intestinal lymphatic delivery. Eur. J. Pharm.
Sci. 2002; 5:405–415.
Nishimukai M, Hara H, Aoyama Y. Enteral
administration of soybean lecithin enhanced
lymphatic absorption of triacylglycerol in rats.
Br. J. Nutr. 2003; 90: 565–571.
Zhang YC, Benet LZ. The gut as a barrier to
drug absorption combined role of cytochrome
P450 3A and P-glycoprotein. Clin.
Pharmacokinet. 2001; 40:159–168.
Seeballuck F, Ashford MB, O’Driscoll CM.
The effects of Pluronics block copolymers and
Cremophor EL on intestinal lipoprotein
processing and the potential link with Pglycoprotein in Caco-2 cells. Pharm. Res.
; 20:1085–1092.
Zhang MY, Morrison RA, Chong S.
Commonly used surfactant, Tween 80,
improves absorption of P-glycoprotein
substrate digoxin, in rats. Arch. Pharm. Res.
:26: 768–772.
Orringer EP, Casella JF, Ataga KI, Koshy M,
Adam-Graves P, Luchtman-Jones L, Wun T,
Watanabe M, Shafer F, Kutlar A, Abboud M,
Steinberg M, Adler B, Swerdlow P, Terregino
C, Saccente S, Files B, Ballas S, Brown R,
Wojtowicz-Praga S, Grindel JM. Purified
Poloxamer 188 for treatment of acute vasoocclusive crisis of sickle cell disease. JAMA
; 286: 2099–2106.
Varshney M, Morey TE, Shah DO, Flint JA,
Moudgil BM, Seubert CN, Dennis DM.
Pluronic® microemulsions as nanoreservoirs
for extraction of bupivacaine from normal
saline. J. Am. Chem. Soc. 2004; 126: 5108–
Siebenbrodt I, Keipert S. Poloxamer-systems
as potential opthalmics II. Microemulsions.
Eur. J. Pharm. Biopharm. 1993; 39: 25–30.
Kataoka K, Kwon GS, Yokohama M, Okano
T, Sakurai Y. Block copolymer micelles as
vehicle for drug delivery. J. Control. Rel.
; 24:119–132.
Batrakova EV, Li S, Alakhov VY, Miller DW,
Kabanov AV. Optimal structure requirements
for Pluronic® block copolymers in modifying
P-glycoprotein drug efflux transporter activity
in bovine brain microvessel endothelial cells.
J. Pharmacol. Exp. Ther. 2003; 304:845–854.
Kabanov AV, Batrakova EV, Alakhov VY.
Pluronic® block copolymers as novel polymer
therapeutics for drug and gene delivery. J.
Control. Rel. 2002; 82: 189–212.
Chen Y, Zhang GGZ, Neilly J, Marsh K,
Mawhinney D, Sanzgiri YD. Enhancing the
bioavailability of ABT-963 using solid
dispersion containing Pluronic F-68. Int. J.
Pharm. 2004; 286: 69–80.
Brusewitz C, Schendler A, Funke A, Wagner
T, Lipp R. Novel poloxamer-based
nanoemulsions to enhance the intestinal
absorption of active compounds. Int. J.
Pharm. 2007; 329:173–181.
Batrakova EV, Han HY, Alakhov VY, Miller
DW, Kabanov AV. Effects of Pluronic®
block copolymers on drug absorption in Caco-
cell monolayers. Pharm. Res. 1998; 15:
–855.
Collett JH, Popli H. Poloxamer. In: Kibbe AH.
(Ed.), Handbook of Pharmaceutical
Excipients, 3rd ed. Pharmaceutical Press,
London, 2000; pp.385–388.
Passerini N, Gonzalez-Rodriguez ML,
Cavallari C, Rodriguez L, Albertini B.
Preparation and Characterization of
ibuprofen–poloxamer 188 granules obtained
by melt granulation. Eur. J. Pharm. Sci. 2002;
:71–78.
Seo A, Holm P, Kristensen HG, Schafer T.
The preparation of agglomerates containing
solid dispersions of diazepam by melt
agglomeration in a high shear mixer. Int. J.
Pharm. 2003; 259: 161–171.
Rouchotas C, Cassidy OE, Rowley G.
Comparison of surface modification and solid
dispersion techniques for drug dissolution. Int.
J. Pharm. 2000, 195:1–6.
Wang Y, Yu L, Han L, Sha X, Fang X.
Difunctional Pluronic copolymer micelles for
paclitaxel delivery: synergistic effect of folatemediated targeting and Pluronic-mediated
overcoming multi-drug resistance in tumor
cell lines. Int. J Pharm. 2007; 337: 63-73.
Chutimaworapan S, Ritthidej GC, Yonemochi
E, Oguchi T, Yamamoto K, Effect of water
soluble carriers on dissolution characteristics
of nifedipine solid dispersions. Drug Dev. Ind.
Pharm. 2000; 26:1141–1150.
Newa M. Preparation, characterization and in
vivo evaluation of ibuprofen binary solid
dispersions with poloxamer 188. Int. J. Pharm.
doi:10.1016/j.ijpharm.2007.05.031
Zimmermann E, Muller RH, Mader K.
Influence of different parameters on
reconstitution of lyophilized SLN. Int. J.
Pharm. 2000; 196: 211-213.
Shahgaldian P, Gualbert J, Aissa K, Coleman
AW. A study of the freeze-drying conditions
of calixarene based solid lipid nanoparticles.
Eur. J. Pharm. Biopharm. 2003; 55: 181-184.
Schwarz C, Mehnert W, Lucks JS, Muller RH.
Solid lipid nanoparticles for controlled drug
delivery. J. Control. Rel. 1994; 30: 83-96.
Weyers H. Feste Lipid Nanopartikel (SLN)
fu¨r die gewebsspezifische
ArzneistoffapplikationHerstellung und
Charakterisierung oberfla chenmodifizierter
ForR. mulierungen, Ph.D. Thesis, Free
University of Berlin, 1995.
Almeida AJ, Runge S, Muller RH. Peptideloaded solid lipid nanoparticles (SLN):
influence of production parameters. Int. J.
Pharm. 1997; 149:255–265.
Boistelle R. Fundamentals of nucleation and
crystal growth, in: N. Garti, K. Sato (Eds.),
Crystallization and, Polymorphism of Fats and
Fatty Acids. Marcel Dekker Inc., New York,
Basel, 1988, pp. 189–226.
Maia CS, Mehnert W, Schafer-Korting M.
Solid lipid nanoparticles as drug carriers for
topical glucocorticoids, Int. J. Pharm. 2000;
:165–167.
Jenning V, Schafer-Korting M, Gohla S.
Vitamin A-loaded solid lipid nanoparticles for
topical use: drug release properties, J. Control.
Rel. 2000; 66: 115–126.
Sato K. Crystallization of fats and fatty acids,
in: Garti N, Sato K. (Eds.), Crystallization and
Polymorphism of Fats and Fatty Acids.
Marcel Dekker Inc., New York, Basel, 1988,
pp. 227–266.
Westesen K, Siekmann B. Investigation of the
gel formation of phospholipid-stabilized solid
lipid nanoparticles. Int. J. Pharm. 1997;
:35–45.
Freitas C, Muller RH. Effect of light and
temperature on zeta potential and physical
stability in solid lipid nanoparticle (SLNE)
dispersions. Int. J. Pharm. 1998; 168:221-229.
R.H. Muller, S. Heinemann, Fat emulsions for
parenteral nutrition. III. Lipofundin
MCT/LCT regimens for parenteral nutrition
(TPN) with low electrolyte load, Int. J. Pharm.
(1994) 175–189.
Laggner P. X-ray diffraction of lipids, in:
Hamilton RJ, Cast J (Eds.), Spectral Properties
of Lipids, Sheffield Academic Press,
Sheffield, 1999, pp. 327–367.
Westesen K, Siekmann B, Koch MHJ.
Investigations on the physical state of lipid
nanoparticles by synchrotron radiation X-ray
diffraction. Int. J. Pharm. 1993; 93:189-199.
Heiati H, Tawashi R, Phillips NC. Solid lipid
nanoparticles as drug carriers - II. Plasma
stability and bio-distribution of solid lipid
noparticles containing the lipophilic prodrug
'-azido-3'-deoxythymidine palmitate in mice,
Int. J. Pharm. 1997;149:255-265.
Chen H, Chang X, Du D, Liu, W, Liu J, Weng
T, Yang Y, Xu H, Yang X. Podophyllotoxinloaded solid lipid nanoparticles for epidermal
targeting J. Control. Rel. 2006; 110: 296-306.
Zur Mühlen A, Mehnert W. Drug release and
release mechanism of prednisolone loaded
solid lipid nanoparticles. Pharmazie 1998;
:552.
Levy MY, Benita S. Drug release from
submicronized o/w emulsion: a new in vitro
kinetic evaluation model. Int. J. Pharm.1990;
: 29-37.
Mueller RH, Solid lipid nanoparticles (SLN)
for controlled drug delivery - a review of the
state of the art. Eur. J. Pharm. Biopharm.
; 50:161-177.
Cavalli R, Gasco MR, Chetoni P, Burgalassi
S, Saettone MF. Solid lipid nanoparticles
(SLN) as ocular delivery system for
tobramycin,
Int. J. Pharm. 2002; 15:241-5.
Greenberg HL, Shwayder, TA, Bieszk, N
Fivenson, DP. Clotrimazole/betamethasone
dipropionate: a review of costs and
complications in the treatment of common
cutaneous fungal infections. Pediatric
Dermatology, 2002; 19, pp. 78-81.
Souto EB, Müller RH. The use of SLN® and
NLC® as topical particulate carriers for
imidazole antifungal agents. Pharmazie, 2006;
, pp; 431-437.
Machlin LJ. 1980. Vitamin E—A
comprehensive treatise. New York and Basel:
Marcel Dekker Inc.
Elmadfa J, Bosse W. Vitamin E. Stuttgart:
Wissenschaftliche Verlagsgesellschaft. 1985.
Mei Z, Chen H, Weng T, Yang Y, Yang X.
Solid lipid nanoparticle and microemulsion for
topical delivery of triptolide. Eur. J. Pharm.
Biopharm. 2003; 56:189–196.
Mei Z, Wu Q, Hu S, Li X, Yang X. Triptolide
loaded solid lipid nanoparticle hydrogel for
topical application. Drug Dev. Ind. Pharm.
; 31:161–168.
Gabard B, Bieli E, Lüdi S. Moderne Konzepte
im Sonnenschutz. Swiss Pharm. 1999; 21: 13–
Wissing SA, Muller RH. Solid lipid
nanoparticles as carrier for sunscreens: in vitro
release and in vivo skin penetration. J Control.
Rel. 2002; 81:225-33.
Wissing SA, Müller RH. A novel sunscreen
system based on tocopherol acetate
incorporated into solid lipid nanoparticles
(SLN). Int. J. Cosm. Sci. 2001a; 23: 233–243.
Zur Mühlen A, Schwarz C, Mehnert W. Solid
lipid nanoparticles (SLN) for controlled drug
delivery—drug release and release
mechanism. Eur. J. Pharm. Biopharm. 1998;
:149–155.
Wissing SA, Muller RH. Solid lipid
nanoparticles (SLN)--a novel carrier for UV
blockers. Pharmazie. 2001; 56:783-6.
Jenning V, Gohla Sh. Encapsulation of
retinoids in solid lipid nanoparticles (SLN1)
journal of microencapsulation, 2001; 18:149-
Wissing SA, Lippacher A, Müller RH.
Investigations on the occlusive properties of
solid lipid nanoparticles (SLNTM). J. Cosm.
Sci. 2001; 52: 313–323.
Demirel M, Yazan Y, Mueller RH, Kilicë
F, Bozan B. Formulation and in vitro ± in vivo
evaluation of piribedil solid lipid micro- and
nanoparticles. J. Microencapsul. 2001; 18:
-371.Muller RH,
Runge S, Ravelli V, Mehnert W,
Thunemann AF, Souto EB. Oral
bioavailability of cyclosporine: Solid lipid
nanoparticles (SLN®) versus drug
nanocrystals. Int. J. Pharm. 2006; 317: 82–89.
Pandey R, Sharma S, Khuller GK. Oral
solid lipid nanoparticle-based antitubercular
chemotherapy. Tuberculosis, 2005; 85: 415–
Poutan CW. Lipid formulations for oral
administration of drugs: non-emulsifying and
self-microemulsifying drug delivery system.
Eur. J. Pharm Sci. 2000; 11:S93-S98.
Porter CJH, Charman WN. Intestinal
lymphatic drug transport: an update. Adv.
Drug Deliv. Rev. 2001; 50:21–44.
Videira MA, Botelho MF, Santos AC,
Gouveia LF, Pedroso de Lima JJ. Almeida AJ.
Lymphatic uptake of pulmonary delivered
radiolabelled solid lipid nanoparticles.
Journal of Drug Targeting, 2002; 10: 607–
Wang JX, Sun X, Zhang ZR. Enhanced
brain targeting by synthesis of 3’, 5’-
dioctanoyl-5-fluoro-2’-deoxyuridine and
incorporation into solid lipid nanoparticles.
Eur J Pharm Biopharm. 2002: 54:285-90.
Goppert TM, Muller RH. Polysorbatestabilized solid lipid nanoparticles as colloidal
carriers for intravenous targeting of drugs to
the brain: Comparison of plasma protein
adsorption patterns. Journal of Drug
Targeting, 2005; 13: 179–187.
Douglas SJ, Davis SS, Illum L.
Biodistribution of poly (isobutylcyanoacrylate) nanoparticles in rabbits. Int. J.
Pharm. 1986; 34:145–152.
Senior JH. Fate and behavior of liposomes
in vivo: A review of controlling factors. Crit.
Rev. Ther. Drug Carrier Syst 1987; 3:123–
Gulyaev AE, Gelperina SE, Skidan IN,
Antropov AS, Kivman GY, Kreuter J.
Significant transport of doxorubicin into the
brain with polysorbate 80-coated
nanoparticles. Pharm Res. 1999; 16:1564–
Alyautdin R, Gothier D, Petrov V,
Kharkevich D, Kreuter J. Analgesic activity of
the hexapeptide dalargin adsorbed on
thesurface of polysorbate 80-coated poly
(butyl cyanoacrylate) nanoparticles. Eur. J.
Pharm. Biopharm. 1999; 41:44–48.
Alyautdin RN, Tezikov EB, Ramge P,
Kharkevich DA, Begley DJ, Kreuter J.
Significant entry of tubocurarine into the brain
of rats by adsorption to polysorbate 80-coated
polybutylcyanoacrylate nanoparticles: An in
situ brain perfusion study. J Microencapsul.
; 15:67–74.
Alyautdin RN, Petrov VE, Langer K,
Berthold A, Kharkewich KA, Kreuter J.
Delivery of loperamide across the blood brain
barrier with polysorbate 80 coated
polybutylcyanoacrylate anoparticles. Pharm.
Res. 1997; 14:43-47
Yang SC, Lu LF, Cai Y, Zhu JB, Liang
BW, Yang CZ.
Body distribution in mice of intravenously
injected camptothecin solid lipid nanoparticles
and targeting effect on brain. J Control. Rel.
; 59:299-307.
Yu BT, Sun X, Zhang ZR. Enhanced liver
targeting by synthesis of N1-stearyl-5-Fu and
incorporation into solid lipid nanoparticles.
Arch Pharm Res. 2003; 26:1096-101.
Reddy LH, Bakshi N, Murthy RSR.
Tamoxifen citrate loaded solid lipid
nanoparticles (SLN™): Preparation,
characterization, in vitro drug release and
pharmacokinetic evaluation. Pharm Dev.
Tech. 2006; 11:167–177.
Wang Y, Deng Y, Mao S, Jin S, Wang J,
Dianzhou Bi. Characterization and body
distribution of b-elemene solid lipid
nanoparticles (SLN). Drug Dev. Ind. Pharm.
; 31:769–778.
Chen, DB, Yang T, Wang-Liang LU,
Zhang Q. In vitro and in vivo study of two
types of long-circulating solid lipid
nanoparticles containing paclitaxel. Chem.
Pharm. Bull. 2001; 49:1444—1447.
