Solid Lipid Nanoparticles: Phagocytic Uptake, in vitro Cytotoxicity and in vitro Biodegradation
Rainer H. MÃ¼ller and Carsten Olbrich
Freie UniversitÃ¤t Berlin, Institut fÃ¼r Pharmazie I (WE1), Pharmazeutische Technologie, Biopharmazie und Biotechnologie, Berlin (Germany)
Dedicated to Prof. Gottfried Heinisch, Institut fÃ¼r Pharmazeutische Chemie, Leopold Franzens UniversitÃ¤t Innsbruck (Austria), on the occasion of his 60th birthday
In the 1st communication of this review it was shown to which extent solid lipid nanoparticles (SLN) are taken up by phagocytosing cells and how the phagocytic uptake can be controlled by surface modification of the particles. SLN uptake by phagocytic cells, e.g. the cells of the mononuclear phagocytic system (MPS), is required to deliver drugs for the treatment of infections localised in these cells, e.g. Mycobacterium avium or M. tuberculosis in the MPS. To utilise the SLN for such diseases the knowledge about the cytotoxicity of the internalised particles and their degradation velocity is essential. In vitro cytotoxicity data are presented using human granulocytes and an HL 60 cell line differentiated to granulocytes. To allow a judgement about the toxicological acceptability, the SLN are compared to other particulate carriers, i.e. polymeric particles (e.g. polylactic acid / glycolic acid). To prove the relevance of the in vitro data, they are compared with first in vivo toxicity studies. The degradation velocity is shown as a function of SLN composition, i.e. lipid and Surfactants / stabilising polymers. The degradation data are used to explain the in vitro and in vivo tolerability and can be utilised to optimise drug release by controlled matrix erosion.
Key words Solid lipid nanoparticles, in vitro biodegradation, in vitro cytotocicity, phagocytic uptake
* ) 1st Communication see Pharm. Ind. 61, no. 6, p. 462 (1998).
pharmind 1999, Nr. 6, Seite 564