In vitro and in vivo study of two types of long-circulating solid lipid nanoparticles containing paclitaxel

Paclitaxel (Taxol), a diterpenoid isolated from Taxus brevifolia, is effect ive against several murine tumors, and is one of the most exciting anticanc er molecules currently available. Due to its low solubility in water, it is clinically administered with polyethoxylated castor oil (Cremophor EL), wh ich causes serious side effects. Inclusion of paclitaxel in solid lipid nan oparticles (SLNs) has proved to be a good approach to eliminate the need fo r Cremophor EL and improve the drug's antitumor efficacy. This paper descri bes the development of two types of long-circulating SLNs as colloidal carr iers for paclitaxel. SLNs are constituted mainly of bioacceptable and biode gradable lipids. In vitro release kinetics showed that the release was very slow, the release of paclitaxel from F-68-SLN is linear, and the release o f paclitaxel from Brij78-SLN followed the Weibull equation. Pharmacokinetic s was evaluated in KM mice after injection of paclitaxel formulated in Crem ophor EL or in Brij78-SLN and F-68-SLN. Encapsulation of paclitaxel in both SLNs produced marked differences compared with the free drug pharmacokinet ics. F-68-SLN and Brij78-SLN are long-circulating (t(1/2)beta, 10.06 and 4. 88 h, respectively) compared with paclitaxel injection (t(1/2)beta, 1.36 h) .