Xiaokuan Li | PubMed Health

PubMed2005

The research on the anti-inflammatory activity and hepatotoxicity of triptolide-loaded solid lipid nanoparticle.

Triptolide (TP) has been shown to have anti-inflammatory, immunosuppressive, anti-fertility and anti-neoplastic activity. However, its clinical use was restricted to some extent due to its serious toxicity. The possible mechanism for triptolide-induced hepatotoxicity was related to reactive oxygen species (ROS) inducing lipid peroxidation and DNA damage. The development of controlled release delivery strategies could lead to significant advantages in the clinical use of these drugs to decreasing the toxicity. Thus, the present study was focused on the preparation and some characterization of triptolide-loaded solid lipid nanoparticle (SLN) and the measurements of anti-inflammatory activities and the hepatotoxicity of TP-SLN. The carrageenan-induced rat paw edema experiment indicated that the anti-inflammatory activities of TP-SLN were stronger than those of free triptolide. Orally administration of TP-SLN 0.2 or 0.4 mg/kg per day did not cause mortality within the period of observation. In contrast, free triptolide at different doses had caused partial death. The serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were significantly elevated in the free triptolide-treated group whereas they did not significantly change in TP-SLN-treated mice. The free triptolide increased malondialdehyde (MDA) level and decreased activities of superoxide dismutase (SOD) and total glutathione peroxidase (GSH-Px) in the liver homogenates. However, these phenomena were not found in TP-SLN-treated mice. The results of histopathological evaluation revealed a protective effect of SLN on vacuolation, edema, inflammatory infiltration and necrosis caused by triptolide. Furthermore, TP-SLN did not change Bcl/Bax protein ratio or decrease FasL expression in liver cells. These results suggest that SLN delivery system can enhance the anti-inflammatory activity of triptolide meanwhile has a protective effect against triptolide-induced hepatotoxicity. The toxicity of TP-SLN to other tissues is under investigation.

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PubMed2005

Triptolide loaded solid lipid nanoparticle hydrogel for topical application.

Triptolide (TP) has been shown to have anti-inflammatory, antifertility, antineoplastic, and immunosuppressive activity. However, its clinical usage is limited to some extent due to its poor water solubility and toxicity. In order to use innovative ways to administer TP and to overcome or alleviate its disadvantages, controlled-release delivery systems such as solid lipid nanoparticle(SLN(s)) have been developed. In the present paper we describe the preparation and some characterization of specialized delivery systems for TP. The transdermal delivery and anti-inflammatory activity were also evaluated. The results indicated that SLN could serve as an efficient promoter of TP penetrating into skin. Furthermore, different formulations were optimized in this study. The best formulation of SLN, consisted of tristearin glyceride, soybean lecithin, and PEG400MS, with a particle size of 123+/-0.9 nm, polydispersity index (PI) of 0.19, and zeta potential of -45 mV. When this SLN dispersion was incorporated into hydrogel, the nanoparticulate structure was maintained, and aggregation and gel phenomena of the particle could be avoided. The cumulative transdermal absorption rate in 12 h was 73.5%, whereas the conventional TP hydrogel was 45.3%. The anti-inflammatory effect is over two-fold higher than that of conventional TP hydrogel. Moreover, this SLN hydrogel consists of pharmaceutically acceptable ingredients, such as soybean lecithin and lipid, and the nanoparticle can improve safety and minimize the toxicity induced by TP.

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