Solid Lipid Nanoparticle

RH Muller, K Mader, S Gohla. Solid lipid nanoparticles (SLN) for controlled drug delivery-A review of the state of the art. Eur J Pharm Biopharm 50(1) 161-177, 2000. 

K Westesen, B Siekmann. Investigation of the gel formation of phospholipid-stabilized solid lipid nanoparticles. Int J Pharm 151(l) 35-45, 1997. 

The production of CLS by the melt dispersion technique is based on the melting of the lipid core material together with the lipophilic agent (i.e., phospholipids). Afterward, a warm aqueous solution is added to the molten material and is mixed by various methods (i.e., mechanical stirring, shaking, sonication, homogenization). Then the preparation is rapidly cooled until lipid solidification and the formation of particle dispersion. This method was used by Olbrich et al. [19] to produce the cationic solid lipid nanoparticles to use as novel transfection agent. 

Olbrich, C., Bakowsky, U., Lehr, C.M., Muller, R.H., and Kneuer, C., Cationic solid-lipid nanoparticles can efficiently bind and transfect plasmid DNA, Journal of Controlled Release, 2001, 77, 345-355. 

Muller, R.H., Ruhl, D., Runge, S., Schulze-Forster, K., and Mehnert, W., Cytotoxicity of solid lipid nanoparticles as a function of the lipid matrix and the surfactant, Pharmaceutical Research, 1997, 14, 458-462. 

Yang, S.C., Zhu, J., Lu, Y., Liang, B., and Yang, C., Body distribution of camptothecin solid lipid nanoparticles after oral administration, Pharmaceutical Research, 1999, 16, 751-757. 

Muller, R.H., Maassen, S., Schwarz, C., and Mehnert, W., Solid lipid nanoparticles (SLN) as potential carrier for human use interaction with human granulocytes, Journal of Controlled Release, 1997, 47, 261-269. 

Olbrich, C. and Muller, R.H., Tabatt, K., Kaiser, O., Schulze, C., and Schade, R., Stable biocompatible adjuvants — a new type of adjuvant based on solid lipid nanoparticles a study on cytotoxicity, compatibility and efficacy in chicken, Alternatives to Laboratory Animals, 2002, 30, 443 158. 

Dingier, A., and Gohla, S., Production of solid lipid nanoparticles (SLN) scaling up feasibilities, Journal of Microencapsulation, 2002, 19, 11-16. 

Muller, R.H., K. Mader, S. Gohla, Solid Lipid Nanoparticles (SLN) for Controlled Drug Delivery A Review of the State of the Art, European Journal of Pharmaceutics and Biopharmaceutics. 50, 161, 2000. 

FIGURE 7.3 Models of drug incorporation into solid lipid nanoparticles. 

Muller, R. H., Radtke, M. and Wissing, S. A., Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) in cosmetic and dermatological preparations. Adv. Drug Deliv. Rev., 54 (Snppl. 1), S131-55, 2002. 

Ahlin, P., Kristi, J. and Smid-Kobar, J., Optimization of procedure parameters and physical stabdity of solid lipid nanoparticles in dispersions. Acta Pharm., 48, 257-67, 1998. 

Siekmann, B. and Westesen, K., Electron-microscopic characterization of melt-homogenized solid lipid nanoparticles. Eur. J. Pharm. Biopharm., 2, 190, 1994. 

Jenning, V, Mader, K. and Gohla, S. H., Solid lipid nanoparticles (SLN) based on binary mixtures of liquid and solid lipids a H-NMR study. Int. J. Pharm., 205, 15-21, 2000. 

Freitas, C. and Muller, R. H., Stability determination of solid lipid nanoparticles (SEN) in aqueous dispersion after addition of electrolyte. J. MicroencapsuL, 16, 59-71, 1999. Bunjes, H., Westesen, K. and Koch, M. H. J., Crystallization tendency and polymorphic transitions in triglyceride nanoparticles. Int. J. Pharm., 129, 159-73, 1996. Freitas, C. and Muller, R. H., Correlation between long-term stability of solid lipid nanoparticles (SLN) and crystallinity of the lipid phase. Eur. J. Pharm. Biopharm., 47, 125-32, 1999. 

Santos Maia, C., et al.. Drug targeting by solid lipid nanoparticles for dermal use. J. Drug Targeting, 10, 489-95, 2002. 

A novel sunscreen system based on tocopherol acetate incorporated into solid lipid nanoparticles has been developed. In recent years, solid lipid nanoparticles (SLN) have been introduced as a novel carrier system for drugs and cosmetics. It has been found that SLN possess characteristics of physical UV-blockers on their own, thus offering the possibility of developing a more effective sunscreen system... 

The extraction of more complex particle size distributions from PCS data (which is not part of the commonly performed particle size characterization of solid lipid nanoparticles) remains a challenging task, even though several corresponding mathematical models and software for commercial instruments are available. This type of analysis requires the user to have a high degree of experience and the data to have high statistical accuracy. In many cases, data obtained in routine measurements, as are often performed for particle size characterization, are not an adequate basis for a reliable particle size distribution analysis. 

The presence and state of solid lipid nanoparticles incorporated into semisolid formulations have also been investigated by DSC [77,83,84]. Using this method, de Vringer and de Ronde were able to draw conclusions on the preparation-dependent distribution of the matrix lipid of their particles in the different phases of a cream formulation [77]. 

The x-ray reflections of solid lipid nanoparticles are usually much broader than those of the bulk material as a result of the small particle size and, potentially, also of a decrease in crystalline order. Fine details may thus not be recognizable in the resulting, more diffuse diffractograms. Assignment of polymorphs may become increasingly difficult with the complexity of the material under investigation (e.g., ) 2005 by CRC Press LLC... 

Transmission electron microscopy (TEM) can provide valuable information on particle size, shape, and structure, as well as on the presence of different types of colloidal structures within the dispersion. As a complication, however, all electron microscopic techniques applicable for solid lipid nanoparticles require more or less sophisticated specimen preparation procedures that may lead to artifacts. Considerable experience is often necessary to distinguish these artifacts from real structures and to decide whether the structures observed are representative of the sample. Moreover, most TEM techniques can give only a two-dimensional projection of the three-dimensional objects under investigation. Because it may be difficult to conclude the shape of the original object from electron micrographs, additional information derived from complementary characterization methods is often very helpful for the interpretation of electron microscopic data. 

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