ナノメディシンとナノテクノロジーのジャーナル

概要

A Self Assembling Nanoemulsion of Lovastatin (SANEL) Decreases Cholesterol Accumulation and Apob-100 Secretion Greater than Lovastatin alone a Hepg2 Cell Line

Srikanth Kakumanu, Swetha Kambalapally and Robert J. Nicolosi

Elevated circulating low density lipoprotein-cholesterol (LDL-C) levels contribute to the development of
cardiovascular disease (CVD). Lovastatin, one of the earliest statins which lowers blood LDL-C and as with the more recent statins, has been reported to reduce mortality due to CVD. However, Lovastatin requires higher doses than other newer statins for optimal efficacy and thus, has been associated with more adverse side effects. The objective of the current study was to test the hypothesis that a self assembling nanoemulsion (SANE) system which would reduce the particle size of typical Lovastatin preparations, and convert this hydrophobic entity to a stable water dispersion could consequently improve its efficacy, as it relates to cellular cholesterol accumulation and apo B (the major apoprotein of LDL) secretion, while lowering the doses needed to produce these results. A SANE Lovastatin (SANEL) and di-methyl sulfoxide (DMSO) Lovastatin (DL) (455 nM) in HepG-2 cell culture system was utilized to examine their effects on cholesterol inhibition and apo B-100 levels at a concentration of 357 nM. Previous work showed that at doses lower than 500 nM, DL had no effect on cholesterol inhibition. SANEL resulted in significantly greater reductions of cellular cholesterol accumulation (53%) and apo B-100 secretion (42%), compared to DL. Thus, a nanoemulsion delivery of Lovastatin as well as other statins may provide an additional method for drug delivery of hydrophobic pharmaceuticals with greater efficacy at lower doses, and possibly fewer side effects.