Solid lipid nanoparticles (SLN) for controlled drug delivery - a review of the state of the art.

Solid lipid nanoparticles (SLN) introduced in 1991 represent an alternative carrier system to traditional colloidal carriers, such as emulsions, liposomes and polymeric micro- and nanoparticles. SLN combine advantages of the traditional systems but avoid some of their major disadvantages. This paper reviews the present state of the art regarding production techniques for SLN, drug incorporation, loading capacity and drug release, especially focusing on drug release mechanisms. Relevant issues for the introduction of SLN to the pharmaceutical market, such as status of excipients, toxicity/tolerability aspects and sterilization and long-term stability including industrial large scale production are also discussed. The potential of SLN to be exploited for the different administration routes is highlighted. References of the most relevant literature published by various research groups around the world are provided.

[1]  Alan Smith,et al.  Evaluation of poly(lactic acid) as a biodegradable drug delivery system for parenteral administration , 1986 .

[2]  R. Cavalli,et al.  Incorporation in lipospheres of [d-Trp-6]LHRH , 1994 .

[3]  R. H. Müller,et al.  Solid Lipid Nanoparticles - ein neuartiger Wirkstoff-Carrier für Kosmetika und Pharmazeutika 2. Mitteilung: Wirkstoff-Inkorporation, Freisetzung und Sterilisierbarkeit , 1997 .

[4]  Otto Caputo,et al.  Albumin adsorption on stealth and non-stealth solid lipid nanoparticles , 1996 .

[5]  R. Cavalli,et al.  Non-stealth and stealth solid lipid nanoparticles (SLN) carrying doxorubicin: pharmacokinetics and tissue distribution after i.v. administration to rats. , 2000, Pharmacological research.

[6]  W. Mehnert,et al.  Drug release and release mechanism of prednisolone loaded Solid Lipid Nanoparticles , 1998 .

[7]  R. Müller,et al.  Solid lipid nanoparticles (SLN) for controlled drug delivery. I. Production, characterization and sterilization , 1994 .

[8]  Maria Rosa Gasco,et al.  Optimization of the incorporation of deoxycorticosterone acetate in lipospheres , 1992 .

[9]  R. Müller,et al.  Solid lipid nanoparticles (SLN) : an alternative colloidal carrier system for controlled drug delivery , 1995 .

[10]  R. Müller,et al.  Phagocytic uptake and cytotoxicity of solid lipid nanoparticles (SLN) sterically stabilized with poloxamine 908 and poloxamer 407. , 1996, Journal of drug targeting.

[11]  H. Bunjes,et al.  Physicochemical characterization of lipid nanoparticles and evaluation of their drug loading capacity and sustained release potential , 1997 .

[12]  R. Müller,et al.  Biodegradation of solid lipid nanoparticles as a function of lipase incubation time , 1996 .

[13]  M. Schäfer-Korting,et al.  Vitamin A-loaded solid lipid nanoparticles for topical use: drug release properties. , 2000, Journal of controlled release : official journal of the Controlled Release Society.

[14]  Rainer H. Müller,et al.  Effect of light and temperature on zeta potential and physical stability in solid lipid nanoparticle (SLN) dispersions , 1998 .

[15]  R. Müller,et al.  Enzymatic degradation of SLN-effect of surfactant and surfactant mixtures. , 1999, International journal of pharmaceutics.

[16]  W Mehnert,et al.  Solid lipid nanoparticles (SLN) for controlled drug delivery--drug release and release mechanism. , 1998, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[17]  M. Schäfer-Korting,et al.  Vitamin A loaded solid lipid nanoparticles for topical use: occlusive properties and drug targeting to the upper skin. , 2000, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[18]  N. Phillips,et al.  Solid lipid nanoparticles as drug carriers: II. Plasma stability and biodistribution of solid lipid nanoparticles containing the lipophilic prodrug 3′-azido-3′-deoxythymidine palmitate in mice , 1998 .

[19]  A.V. Kovalyov An O , 1995, Proceedings of Tenth International Symposium on Intelligent Control.

[20]  Future strategies for drug delivery with particulate systems , 1998 .

[21]  K. Westesen,et al.  Investigations on the physical state of lipid nanoparticles by synchrotron radiation X-ray diffraction , 1993 .

[22]  C. Bocca,et al.  Phagocytic uptake of fluorescent stealth and non-stealth solid lipid nanoparticles , 1998 .

[23]  R. Cavalli,et al.  Solid lipospheres obtained from hot microemulsions in the presence of different concentrations of cosurfactant : the crystallization of stearic acid polymorphs , 1993 .

[24]  K. Mäder,et al.  Solid lipid nanoparticles (SLN™) based on binary mixtures of liquid and solid lipids: a 1H-NMR study , 2000 .

[25]  R. Cavalli,et al.  Solid lipospheres of doxorubicin and idarubicin , 1993 .

[26]  H. Bunjes,et al.  Do nanoparticles prepared from lipids solid at room temperature always possess a solid lipid matrix , 1995 .

[27]  J. E. Diederichs,et al.  Liposome in Kosmetika und Arzneimitteln , 1994 .

[28]  K. Westesen,et al.  Thermoanalysis of the recrystallization process of melt-homogenized glyceride nanoparticles , 1994 .

[29]  A. Domb,et al.  Insect repellent formulations of N,N-diethyl-m-toluamide (deet) in a liposphere system: efficacy and skin uptake. , 1995, Journal of the American Mosquito Control Association.

[30]  R. Müller,et al.  Correlation between long-term stability of solid lipid nanoparticles (SLN) and crystallinity of the lipid phase. , 1999, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[31]  M. Trotta,et al.  Sterilization and freeze-drying of drug-free and drug-loaded solid lipid nanoparticles , 1997 .

[32]  Y. Cai,et al.  Body distribution in mice of intravenously injected camptothecin solid lipid nanoparticles and targeting effect on brain. , 1999, Journal of controlled release : official journal of the Controlled Release Society.

[33]  R. H. Müller,et al.  Solid lipid nanoparticles : ein neuartiger Wirkstoff-Carrier für Kosmetika und Pharmazeutika. 3. Mitteilung: Langzeitstabilität, Gefrier- und Sprühtrocknung, Toxizität, Anwendung in Kosmetika und Pharmazeutika , 1997 .

[34]  R. Müller,et al.  Interaction of differentiated HL60 cells with poloxamer and poloxamine surface modified model drug carriers , 1997 .

[35]  R. Müller,et al.  Stability determination of solid lipid nanoparticles (SLN) in aqueous dispersion after addition of electrolyte. , 1999, Journal of microencapsulation.

[36]  R. Shivers,et al.  Solid lipid nanoparticles as drug carriers. I. Incorporation and retention of the lipophilic prodrug 3′-azido-3′-deoxythymidine palmitate , 1997 .

[37]  N. Garti,et al.  Crystallization and polymorphism of fats and fatty acids , 1988 .

[38]  園部 尚 Future Strategies for Drug Delivery with Particulate Systems , 1999 .

[39]  R. Cavalli,et al.  Timolol in lipospheres. , 1992, Die Pharmazie.

[40]  Heike Bunjes,et al.  Crystallization tendency and polymorphic transitions in triglyceride nanoparticles , 1996 .

[41]  E. Peira,et al.  Solid lipid nanoparticles as carriers of hydrocortisone and progesterone complexes with β-cyclodextrins , 1999 .

[42]  R. Cavalli,et al.  Preparation and characterization of solid lipid nanospheres containing paclitaxel. , 2000, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[43]  S. Benita Submicron Emulsions in Drug Targeting and Delivery , 2019 .

[44]  R. Müller,et al.  Pellets as carriers of solid lipid nanoparticles (SLN) for oral administration of drugs , 1999 .

[45]  R. Müller,et al.  Fat emulsions for parenteral nutrition. III: Lipofundin MCT/LCT regimens for total parenteral nutrition (TPN) with low electrolyte load , 1994 .

[46]  R. Cavalli,et al.  Preparation and evaluation in vitro of colloidal lipospheres containing pilocarpine as ion pair , 1995 .

[47]  G. G. Stokes "J." , 1890, The New Yale Book of Quotations.

[48]  J. Kristl,et al.  Location of lipophilic substances and ageing of solid lipid nanoparticles studied by EPR , 2000 .

[49]  Emilio Marengo,et al.  Effects of some experimental factors on the production process of solid lipid nanoparticles , 1996 .

[50]  R. Müller,et al.  Solid lipid nanoparticles (SLN) for controlled drug delivery , 1996 .

[51]  S. Gohla,et al.  Medium scale production of solid lipid nanoparticles (SLN) by high pressure homogenization , 2002, Journal of microencapsulation.

[52]  R. Müller,et al.  Solid lipid nanoparticles (SLN/Lipopearls)--a pharmaceutical and cosmetic carrier for the application of vitamin E in dermal products. , 1999, Journal of microencapsulation.

[53]  R. Cavalli,et al.  Thymopentin in solid lipid nanoparticles , 1996 .

[54]  E. Terreno,et al.  NMR relaxometric investigations of solid lipid nanoparticles (SLN) containing gadolinium(III) complexes. , 1998, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[55]  K. Westesen,et al.  Investigation of the gel formation of phospholipid-stabilized solid lipid nanoparticles , 1997 .

[56]  R. Müller,et al.  Solid lipid nanoparticles (SLN) as potential carrier for human use: interaction with human granulocytes , 1997 .

[57]  T. de Vringer,et al.  Preparation and structure of a water-in-oil cream containing lipid nanoparticles. , 1995, Journal of pharmaceutical sciences.

[58]  A. Domb Long acting injectable oxytetracycline-liposphere formulations , 1995 .

[59]  R. Müller,et al.  Formulation and in vitro-in vivo evaluation of piribedil solid lipid micro- and nanoparticles , 2001, Journal of microencapsulation.

[60]  E. Marengo,et al.  THE EFFECT OF ALCOHOLS WITH DIFFERENT STRUCTURES ON THE FORMATION OF WARM O/W MICROEMULSIONS , 1996 .

[61]  N. Phillips,et al.  Drug retention and stability of solid lipid nanoparticles containing azidothymidine palmitate after autoclaving, storage and lyophilization. , 1998, Journal of microencapsulation.

[62]  R. Müller,et al.  Cytotoxicity of magnetite-loaded polylactide, polylactide/glycolide particles and solid lipid nanoparticles , 1996 .

[63]  K. Westesen,et al.  Investigations on solid lipid nanoparticles prepared by precipitation in o/w emulsions , 1996 .

[64]  R. Müller,et al.  Solid lipid nanoparticles (SLN)--a novel carrier for UV blockers. , 2001, Die Pharmazie.

[65]  R. Müller,et al.  Spray-drying of solid lipid nanoparticles (SLN TM). , 1998, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[66]  Donald L. Wise,et al.  Handbook of Pharmaceutical Controlled Release Technology , 2000 .

[67]  W Mehnert,et al.  Solid lipid nanoparticles (SLN) for controlled drug delivery. II. Drug incorporation and physicochemical characterization. , 1999, Journal of microencapsulation.