Lipid Spheres as Attractive Nanoscale Drug Delivery Platforms for Cancer Therapy

Several barriers limit the effective tumor delivery and penetration of the nanomedicine candidates as anti-cancer therapeutics, including: [1] heterogeneous tumor circulation caused by abnormal and irregular architecture of the tumor vasculature, [2] intratumoral vascular hyperpermeability contributing to increased interstitial pressure in the targeted tumor that substantially reduces the convective transport of nanoparticles and [3] impaired diffusion in the context of an abnormal and highly dense extracellular collagen matrix in the tumor microenvironment.Lipid spheres represent a promising drug formulation platform for effective delivery of anti-cancer pharmaceuticals to target cancer cells.Lipid spheres, especially microemulsion systems can be used to address various challenges in formulation and clinical use of anti-cancer pharmaceuticals.Due to a number of attributes inherent to lipid sphere nanoparticles, including their large lipid cores for the solubilization of anti-tumor agents, and the relative ease of lipid sphere manufacturing compared to the manufacturing of liposomes, lipid spheres have the potential to emerge as the preferred nanoscale delivery systems of anti-cancer therapeutics.Low Interfacial Tension Lipid Spheres (LIFT-LS) are classical thermodynamically stable microemulsions.LIFT of the nanoscale microemulsion systems and many of their LIFT-associated surface characteristics such as enhanced nanodroplet deformability, flexibility, and ease of emulsification at the contact point between the microemulsion nanodroplets and the target cancer cell membrane may contribute to an improved drug delivery capacity.The ability of the microemulsion nanodroplets to undergo shape changes and fragmentationcoalescence when subjected to environmental perturbations may further facilitate their transport and penetration through the extracellular tumor matrix despite high interstitial tissue pressure that exists inside solid tumors.Dilutable Low Interfacial Tension Lipid Spheres (DLIFT-LS) are a distinct subgroup of LIFT-LS and currently represent the most advanced form of microemulsions.It is our considered opinion that DLIFT-LS are the most suitable lipid spheres for intravenous anti-cancer drug delivery due to their multiple attributes as discussed in this review.