Sorafenib is a novel antitumor drug,which is poorly absorbed in the gastrointestinal tract due to its low solubility in water.To improve the bioavailability of sorafenib,a self-microemulsifying drug delivery system(SMEDDS) formulation of sorafenib was prepared and its relative bioavailability in rats was evaluated.The blank SMEDDS was prepared from a mixture of ethyl oleate(oil phase,20%,w/w),Cremophol EL(surfactant,48%,w/w),PEG-400(co-surfactant,16%,w/w) and ethanol (co-surfactant,16%,w/w).Sorafenib was subsequently dissolved in the blank SMEDDS to obtain a sorafenib SMEDDS formulation with a final sorafenib concentration at 20 mg/mL.The particle size of the emulsified sorafenib SMEDDS was about 20-25 nm. Compared with sorafenib suspension,the prepared SMEDDS formulation exhibited no effect on the T_(max),but significantly increased the AUC,C_(max) and MRT and decreased the drug clearance.Most importantly,the oral bioavailability based on AUC_(0-72h) increased about 25 times after formulating sorafenib in SMEDDS.We concluded that SMEDDS could be a promising vesicle for the oral delivery of the poorly soluble antitumor drug sorafenib.
With increasing knowledge of the molecular mechanisms of endogenous RNA interference,systemic delivery of small interfering RNA（siRNA） via targeted nanoparticles has emerged as a potential strategy for cancer gene therapy.In this study,a novel formulation[liposome-protamine-chondroitin sulfate nanoparticles（LPC-NP）]was developed for siRNA delivery by self-assembling with charge-charge interaction.The LPC-NP was further modified by DSPE-PEG_（2000） and DSPE-PEG_（2000）-T7 by the post-insertion method.T7,a transferrin-like seven-amino acid peptide,is a targeting ligand for transferrin receptor-overexpressed MCF-7 breast cancer cells.The particle size and zeta potential of LPC-NP were approximately 90 nm and ＋35 mV,respectively. It was shown that PEG modification could significantly decrease aggregation of LPC-NP in serum,and T7 peptide modified LPC-NP could significantly increase the cellular uptake and the gene-silencing effect of siRNA.In vitro cytotoxicity assay exhibited that significant cell growth inhibition was achieved in MCF-7 cells after the delivery of anti-EGFR siRNA.Our encouraging results suggested that T7-modified LPC-NP might be a promising carrier for RNAi-based tumor therapy.
