Synthetic lipid nanoparticles targeting steroid organs.
Lipidots are original nanoparticulate lipid delivery vectors for drugs and contrast agents made from materials generally regarded as safe. Here, we characterized the in vivo stability, biodistribution, and pharmacokinetics of lipidots.


METHODS
Lipidots 55 nm in diameter and coated with a phospholipid/poly(ethyleneglycol) surfactant shell were triply labeled with (3)H-cholesteryl-hexadecyl-ether, cholesteryl-(14)C-oleate, and the 1,1'-dioctadecyl-3,3,3',3'-tetramethylindotricarbocyanine infrared fluorescent dye and injected intravenously into immunocompetent Friend virus B-type mice. The pharmacokinetics and biodistribution of lipidots were analyzed quantitatively in serial samples of blood and tissue and with in vivo optical imaging and were refined by microscopic examination of selected target tissues.


RESULTS
The plasmatic half-life of lipidots was approximately 30 min. Radioactive and fluorescent tracers displayed a similar nanoparticle-driven biodistribution, indicative of the lipidots' integrity during the first hours after injection. Lipidots distributed in the liver and, surprisingly, in the steroid-rich organs adrenals and ovaries, but not in the spleen. This tropism was confirmed at the microscopic level by histologic detection of 1,1'-dioctadecyl-3,3,3',3'-tetramethylindotricarbocyanine. Nanoparticle loading with cholesterol derivatives increased accumulation in ovaries in a dose-dependent manner.


CONCLUSIONS
This previously unreported distribution pattern is specific to lipidots and attributed to their nanometric size and composition, conferring on them a lipoproteinlike behavior. The affinity of lipidots for steroid hormone-rich areas is of interest to address drugs and contrast agents to lipoprotein-receptor-overexpressing cancer cells found in hormone-dependent tumors.
Inserm U1023, I2BM/SHFJ, CEA, Orsay, France.
Juliette
J
Mérian
Raphaël
R
Boisgard
Xavier
X
Decleves
Benoît
B
Thezé
Isabelle
I
Texier
Bertrand
B
Tavitian
D000818:Animals; D002626:Chemistry, Pharmaceutical; D002784:Cholesterol / Q000378:metabolism; D004337:Drug Carriers / Q000138:chemical synthesis* / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D005260:Female; D008055:Lipids / Q000138:chemical synthesis* / Q000737:chemistry* / Q000493:pharmacokinetics; D051379:Mice; D053758:Nanoparticles; D013229:Stearic Acids / Q000378:metabolism; D013256:Steroids / Q000378:metabolism*
D004337:Drug Carriers; D008055:Lipids; D013229:Stearic Acids; D013256:Steroids; C031183:stearic acid; D002784:Cholesterol
biodistribution; in vivo imaging; lipid nanoparticles; lipoproteins; pharmacokinetics