Solid lipid nanoparticles (SLN) - Effects of lipid composition on in vitro degradation and in vivo toxicity

• Type: Article in International Scientific Journal
• Date: 2006

Authors

Weyhers, H (Author) Other; Ehlers, S (Author) Other; Hahn, H (Author) Other; Souto, EB (Author) Other; Muller, RH (Author) Other

Journal

The Journal is awaiting validation by the Administrative Services.

Title: PHARMAZIE

Vol. 61

Pages: 539-544

ISSN: 0031-7144

Indexing

Scopus - 55 Citations

Other information

Authenticus ID: P-00F-S99

Abstract (EN): Solid lipid nanoparticles (SLN) composed of two different lipid matrices were produced to assess their in vivo toxicity in mice. Matrix substances were (i) Compritol (glycerol behenate), a physiological lipid with GRAS status (generally recognized as safe [FDA]), and (ii) cetyl palmitate, a less physiological compound. Physicochemical data proved the suitability of SLN batches for intravenous administration. To assess the in vivo toxicity of produced batches, 400 ¿l SLN dispersion (lipid content 10% [m/m]) were administered to mice via a bolus injection for six times within a period of 20 days (high dose administration). Additionally, a multiple low dose administration was performed with Compritol-SLN as well (200 ¿l SLN dispersion, lipid content 2.5% [m/m]). Hepatic and splenic tissues were analysed histologically. In vivo results were dependent on the lipid matrix, as well as on the dose administered. For cetyl palmitate containing SLN no pathological results were obtained, while high dosed Compritol containing formulations led to accumulation of the lipid in liver and spleen and subsequently to pathological alterations. These alterations were found to be partially reversible within six weeks after completing intravenous administration. Liver architecture was nearly recovered. In contrast, low dosed Compritol SLN were well tolerated. Lipid accumulation and pathological alterations of high dosed Compritol SLN were attributed to the slow degradation of the Compritol matrix which could be shown by performing in vitro studies in human plasma.

Language: English

Type (Professor's evaluation): Scientific