While expression of "lipoprotein receptors" has been reported for various tumor cell types, there are certain other lesions which consistently display a similarly increased (cell-surface) expression and/or activity of such lipoprotein receptors, which includes notably the (class B) scavenger receptor referred to as SR-BI [cf. recent book: D'Arrigo, J.S. (2011) Stable Nanoemulsions: Self-Assembly in Nature and Nanomedicine, 436 pp., Elsevier Science, Amsterdam and Oxford]. (Such data on SR-BI expression and function are noteworthy since, as described previously for drug delivery to tumor cells [see D'Arrigo (2011) reference above], SR-BI has emerged as the lipoprotein receptor primarily involved in the enhanced endocytosis of "lipid-coated microbubbles (LCM)/nanoparticle-derived" nanoemulsions into various tumor cells.) Hence, for the other (noncancerous) disease/injury sites which overexpress (cell-surface) SR-BI, suitable targeted drug-delivery therapy of that given disease or injury, via the above (e.g., FilmixTM) nanoemulsion, becomes more practicable (see below).
The corporation's (injectable) nanoemulsion formulations, which are especially useful for "actively targeted" chemotherapy, comprise several key lipid components that can be adjusted for specific applications. [For a detailed review of the relevant scientific and patent literature, associated know-how, advantages over competing technologies, target markets, etc., see D'Arrigo (2011) reference above.] Briefly, the above 2011 book reviews and analyzes much experimental (in vivo) data which collectively demonstrate that this type of stable lipid nanoemulsion, upon intravenous injection, is capable of "active targeting" of various lipophilic drugs to hyperproliferative-disease sites -- which commonly overexpress certain cell-surface receptors, including SR-BI.
An example of the above-mentioned "other (noncancerous) disease/injury sites" (involving proliferative processes), which overexpress scavenger receptors, concerns central-nervous-system (CNS) injury -- that is, brain injury and/or spinal cord injury. Various published studies indicate increased scavenger receptor expression on "proliferating macrophages" and "activated astrocytes" arising after CNS injury [D'Arrigo (2011) reference above]. In this regard, the findings of Kureshi et al. [Neurosurgery 44:1047-1053 (1999)] have direct relevance to Filmix-related lipid nanoemulsions, that is, LCM and particularly "dispersed LMN" (see below). As reviewed earlier (in greater detail in Sect. 14.2.2.2 of D'Arrigo (2011) reference above), these investigators reported that LCM [and/or agglomerations of the far more numerous and smaller "dispersed LMN" (undecipherable at that time)] in Filmix agent, injected intravenously, displayed a readily measurable affinity to injured rat spinal cord. It was observed, using fluorescent labeling and confocal laser scanning microscopy, that the affinity of LCM (and/or dispersed LMN) for spinal cord injury sites appears to be mediated in the early stages after injury by proliferating macrophages in the necrotic center, and then in later stages by activated astrocytes in adjacent white matter [Kureshi et al., Neurosurgery 44:1047-1053 (1999)].
As another application of LCM (and/or dispersed lipid-mesophase nanoparticles (LMN)) to CNS injury, Ho et al. [Brain Res. Bull. 43:543-549 (1997)] studied the affinity of LCM to the site of a localized (thermal) brain injury. As reviewed earlier (in more detail in Sect. 14.2.2.2 of D'Arrigo (2011) reference above), these authors point out it had been well documented earlier that in response to injury in the CNS, astrocytes are activated; this process is accompanied by an increased content of GFAP, hypertrophy, and hyperplasia [Bignami & Dahl, Neuropath. Appl. Neurobiol. 2:99-110 (1976); Mathewson & Berry, Brain Res. 327:61-69 (1985); Miyake et al., Brain Res. 590:300-302 (1992); Nieto-Sampedro et al., Brain Res. 343:320-328 (1985); Schiffer et al., Brain Res. 374:110-118 (1986)] -- a process referred to as gliosis [Nieto-Sampedro et al., Brain Res. 343:320-328 (1985)]. In particular, Ho et al. observed that the influx of LCM began at the time when GFAP-positive cells began to appear, and it seemed likely that the LCM are initially attracted to the "reactive" astrocytes [Brain Res. Bull. 43:543-549 (1997)]. In follow-up to these findings with brain injury, the experiment program with LCM (and/or dispersed LMN) was expanded to next examine the use of LCM to deliver 7B-hydroxycholesterol (7B-OHC) to a radiofrequency (thermal) lesion in the rat brain [Wakefield et al., Neurosurgery 42:592-598 (1998)]. (7B-OHC and other oxysterols have been reported, by other investigators, to inhibit astrogliosis as well as tumor cell proliferation both in vitro and in vivo [see D'Arrigo (2011) book above for listing of cross-references]). The data obtained in this follow-up study indicate that both the number of activated astrocytes and the intensity of the GFAP-staining were reduced when treated with 7B-OHC delivered by the LCM, while not affected by the same dose of intravenously injected 7B-OHC in saline [Wakefield et al., Neurosurgery 42:592-598 (1998)]. It appears that the mechanism of this enhanced delivery of 7B-OHC to the brain-injury site by LCM (and/or dispersed LMN) shares common features with the "receptor (i.e., SR-BI)-mediated endocytic pathway" mechanism described earlier for the case of tumor cells [cf. Sect. 24.3 of D'Arrigo (2011) reference above]. This interpretation of the data receives additional indirect support from published findings, of other investigators, which document the expression of SR-BI on astrocytes and vascular smooth muscle cells in adult mouse and human brains (as well as in Alzheimer's disease brain [Husemann & Silverstein, Am. J. Pathol. 158:825-832 (2001)]).
Therefore, the ultimate objective of "targeted chemotherapy" of neuro-injury sites, utilizing "active targeting" behavior of an intravenous agent, is particularly well-suited to the Filmix nanoemulsion drug-delivery vehicle -- since SR-BI has emerged as the lipoprotein receptor primarily involved in ligand-receptor binding of this lipid nanoemulsion vehicle at target cells [D'Arrigo (2011) reference above].