Cholesteryl butyrate in solid lipid nanospheres as an alternative approach for butyric acid delivery.
BACKGROUND
Cholesteryl-butyrate chosen as lipid matrix of solid lipid nanospheres (SLNs) could be a suitable pro-drug to deliver butyric acid and overcome one of the most limiting disadvantages of the compound: the short half-life due to a rapid metabolism.


METHODS
We evaluated the antiproliferative effect, with respect to that of sodium butyrate, of four SLNs (SLN1, SLN2, SLN3 and SLN4) characterized by a different concentration of cholesteryl-butyrate (range, 1.7-30 mM) on NIH-H460, a non-small cell lung carcinoma cell line.


RESULTS
After 6 days of treatment, all SLN preparations induced a dose-dependent inhibition of NHI-H460 cell growth: the most effective SLN preparation (SLN1) was able to induce a complete growth inhibition already at 0.25 mM, a concentration at which sodium butyrate induced only a 55% inhibition. Fluorescence microscopy showed that 6-coumarin-tagged SLNs were almost completely internalized by cells after 5 min of treatment.


CONCLUSIONS
The present results indicate that owing to their peculiar characteristics, SLNs could be an interesting alternative approach for butyric acid delivery into tumor cells.
Pellizzaro
C
C
Unità Operativa Determinanti Biomolecolari nella Prognosi e Terapia, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milano, Italy.
Coradini
D
D
Morel
S
S
Ugazio
E
E
Gasco
M R
MR
Daidone
M G
MG
D002087:Butyrates / Q000493:pharmacokinetics*; D020148:Butyric Acid / Q000493:pharmacokinetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002784:Cholesterol / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics*; D006801:Humans; D008055:Lipids / Q000737:chemistry / Q000493:pharmacokinetics*; D008175:Lung Neoplasms / Q000378:metabolism; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D010713:Phosphatidylcholines / Q000493:pharmacokinetics; D014407:Tumor Cells, Cultured
D002087:Butyrates; D004337:Drug Carriers; D008055:Lipids; D010713:Phosphatidylcholines; D020148:Butyric Acid; D002784:Cholesterol