A novel vitamin E form, RRR-α-tocopherol ether-linked acetic acid analogue (α-TEA), has been reported by our lab to exhibit antitumor properties in studies of human tumor cells in culture and nude mouse xenograft models as well as a syngeneic BALB/c 66-4-GFP mouse mammary tumor model. α-TEA has been formulated in liposomes in order to improve drug delivery and anticancer efficacy. Liposome formulation is an established colloidal drug delivery system, but there are several limitations, such as difficulty in storage, stability and rapid drug leakage. Biodegradable polymeric nanoparticle systems are designed to avoid such limitations and studies show that nanoparticles produce higher intracellular drug concentrations, possess an ability to protect the drug from degradation by lysosomes and help control drug release rate. An emulsion evaporation method has been used to develop a biodegradable polymeric nanoparticle system. An in vivo animal study using the syngeneic BALB/c mammary cancer mouse model has been carried out to evaluate the effect of the nanoparticle versus liposome formulations in decreasing tumor burden and reducing lung metastasis. α-TEA formulated in liposomes or nanoparticles and delivered orally at 5 mg/day significantly reduced tumor burden as well as number of mice with visible lung metastases, mean number of visible lung metastases/mouse and mean number of microscopic lung metastases/mouse; whereas, α-TEA formulated by the two methods and delivered orally at 2.5 mg/day was less effective in reducing tumor burden and both visible and microscopic lung metastases. At both doses, α-TEA formulated in nanoparticles performed significantly better than α-TEA formulated in liposomes in reducing tumor burden (p< 0.001). Animals receiving nanoparticle control, in comparison to liposome control, exhibited reduced tumor burden but no decrease in visible lung metastases. Immunohistological analyses (TUNEL and CD31 staining assays) of 5 micron tumor sections are currently in progress. Supported by CA 59739,the Foundation for Research and ES07784.
[Proc Amer Assoc Cancer Res, Volume 47, 2006]