An injectable nanoemulsion formulation has been developed, by Cav-Con Inc., which is especially useful for highly selective delivery of incorporated (lipophilic) imaging agents to various types of solid tumors [-- see www.netplex.net/~cavcon for sample micrographs, peer-reviewed publications, and past patents]. This stable (nontoxic) lipid nanoemulsion, containing both colloidal "lipid-coated microbubbles" (LCM) and related lipid nanoparticles, is capable of "active targeting" to various tumors via the process of receptor-mediated endocytosis. Hence, this "LCM/nanoparticle-derived" lipid formulation (i.e., FilmixTM) has been used successfully, in animals, as a selective delivery agent that "actively" targets high-contrast imaging agents toward different tumor cells that commonly overexpress certain surface receptors, which fall within the category known as "lipoprotein receptors". Moreover, the "LCM/nanoparticle-derived" lipid nanoemulsion contains no phospholipids, no proteins nor peptides, and no carbohydrates (and incorporation of lipophilic imaging molecules [such as lipophilic dyes, in the past] has not required any chemical modification of the imaging agent). Consequently, this category of parenteral lipid nanoemulsion avoids various past problems reported for earlier versions of (actively) targeted delivery agents utilizing such lipoprotein-receptor-mediated endocytic pathway(s). [ For a detailed review of the relevant scientific and patent literature, associated know-how, advantages over competing technologies, target markets, etc., see recent book: D'Arrigo, J.S. (2011) Stable Nanoemulsions: Self-Assembly in Nature and Nanomedicine, 436 pp., Elsevier Science, Amsterdam and Oxford.]
This "active" targeting behavior of the Filmix lipid nanoemulsion vehicle via lipoprotein-receptor-mediated endocytosis, which includes notably the (class B) scavenger receptor referred to as SR-BI, has direct relevance to the selective delivery of high-contrast imaging agents to different tumors. Specifically, overexpression of the SR-BI receptor (or its human homologue, CLA-1) has long been found, and reported repeatedly in the literature [e.g., Neoplasia 13:309-391 (2011); J. Drug Target. 18 :53-58 (2010); Biol. Reprod. 81:365 (2009); Cancer Res. 64:1515-1521 (2004); Biochim. Biophys. Acta 1485:129-144 (2000); Biochem. J. 349:559-566 (2000)], to be associated with the surface-membrane pathophysiology of malignant breast-tumor cells.
The lipid nanoemulsion delivery vehicle itself, i.e., the Filmix formulation, comprises several key lipid components that can be adjusted for specific applications. Briefly, the Filmix nanoemulsion is constructed entirely of nonionic lipids -- i.e., saturated glycerides, cholesterol, and cholesterol esters. In addition, this lipid composition (of the Filmix colloidal system, i.e., glycerides and cholesterol compounds) is similar to lipids contained in several types of plasma lipoproteins. Accordingly, when these Filmix colloidal particles (i.e., LCM and related lipid nanoparticles) are injected into the bloodstream, they acquire (bind) plasma apolipoprotein(s) -- which are evidently recognized by the corresponding lipoprotein receptors (often found overexpressed on the surface membrane of tumor cells); specifically, confocal laser microscopy clearly demonstrates successful tumor-selective endocytosis of the Filmix lipid particles [J. Neuro-Oncology 26:25-34 (1995)]. The measured lipid nanoemulsion particle uptake by target cells (tumor cells) displays both temperature dependence and energy dependence. Moreover, this Filmix nanoemulsion delivery vehicle is physically capable of carrying high-contrast imaging agents (for example, lipophilic dyes [or other small lipophilic molecules for other imaging modalities]) with these nanoemulsion particles into the target cells [cf. D'Arrigo (2011) reference above].