The remarkable polymorphic or phase behaviors of lipid/water systems, especially as concerns saturated monoglycerides, have been elaborately documented in the chemical literature [for a detailed review, see D'Arrigo (2011) Stable Nanoemulsions: Self-Assembly in Nature and Nanomedicine, 436 pp.; Elsevier, Amsterdam and Oxford]. These phase behaviors and associated liquid-crystal transitions can be quite complex and varied. ( Note that the term "liquid crystal" itself is defined as a phase that has mobility like that of a liquid, as well as a high degree of order like that in a crystal; also known as a "mesophase" or "mesomorphic phase" [Stenesh (1975) Dictionary of Biochemistry, Wiley].) When the aqueous concentration of an amphiphilic lipid with a single hydrocarbon chain (such as the saturated monoglyceride which is the predominant lipid in the Filmix® nanoemulsion) is raised to sufficiently high values, ordered liquid-crystalline phases are formed. As the amphiphilic single-chain lipid (e.g., monoglyceride) concentration is further increased, several successive phase transitions occur [e.g., Tanford (1973) The Hydrophobic Effect, Wiley]. Such self-assembly of varied and useful liquid-crystalline phases depends heavily on the acyl chain length of the (saturated) monoglycerides placed in contact with water [ literature reviewed in D'Arrigo (2011) reference above].
These dispersed liquid-crystalline lipid particles, of "LCM/nanoparticle-derived" nanoemulsions (such as Filmix® nanoemulsion), are colloidally stable nanostructures. Such nanoemulsion particles, representing inverse-type (inverse topology or type II) liquid-crystalline phases [ D'Arrigo, (2011) reference above], include a popular family of cubic-symmetry lipid phases that continue to attract much attention currently due to their great potential for applications in pharmaceutical, cosmetic, and food industries. For example, the formulation of these dispersed (inverse topology) cubic lipid phases is attractive due to the possibility of combining the solubilization capacity for lipophilic drugs with their controlled release [e.g., Salentinig et al. (2008) J. Colloid Interface Sci. 326:211-220]. In particular, an advantage of nonlamellar structures, such as inverse cubic phases, is the increased surface area generated by their inherent nanostructure. Such nanostructured liquid-crystalline lipid phases (i.e., submicron dispersions of lipid mesophases) are also much more robust, when compared to liposomal delivery technologies, by virtue of their semirigid periodicity [e.g., Fong et al. (2007) J. Phys. Chem. B 111:1384-1392; cf. D'Arrigo (2011) reference above].
To summarize the findings specifically regarding targeted drug delivery (using such nanoemulsions) in animals, various types of in vivo data obtained indicate that paclitaxel can be lastingly incorporated into the ("LCM/nanoparticle-derived") lipid nanoemulsion particles. Further, the in vivo treatment in rats using two different tumor models (C6 glioma in Sprague-Dawley rats, and 9L glioma in Fischer 344 rats) indicated that an intravenously injected paclitaxel-"LCM/nanoparticle" population can be selectively delivered to the tumor site, and can exert not only a measurable biological effect but also an enhanced antitumor activity (as compared to the free drug) [ Ho et al. (1997) Neurosurgery 40:1260-1268; and D'Arrigo (2003) Stable Gas-in-Liquid Emulsions, 2nd edition, Elsevier].
A similar targeted drug-delivery situation has been reported for the case of brain-injury sites. This intracellular uptake, of such targeted "LCM/nanoparticle-derived" nanoemulsions, by the neuro-injury target tissue was observed as early as 2 minutes after intravenous injection [ Wakefield et al. (1998) Neurosurgery 42:592-598; and D'Arrigo (2003) reference above]. This related drug-delivery study demonstrated that 7β-hydroxycholesterol (7β-OHC), delivered in the "LCM/nanoparticle" population, exerts an antigliosis (therapeutic) effect in the rat-brain-injury model. Moreover, as observed previously with the drug paclitaxel, delivery of 7β-OHC to the neuro-injury site via the "LCM/nanoparticle" population appears to greatly magnify the concentration of that drug reaching the target site [see Wakefield et al. (1998) and D'Arrigo (2003) references above; cf. D'Arrigo (2011) reference above].