Squalene is an acyclic triterpene with the molecular formula (C5H8)6. It is named because it exists in shark liver oil. However, it is widely distributed in nature and is found in abundance in olive oil and olive leaves. Squalene contains two farnesol moieties connected in a tail-to-tail fashion. Therefore, the 6 double bonds, 10 methylenes, and 8 methyl groups are symmetrically distributed in respect of the C12-C13 bonding. Squalene is the corner stone in the biosynthesis of most triterpenes, including lanosterol and cycloartenol, which in turn are the precursors of steroids. The dynamically folded conformation of squalene has been used to chemically couple various therapeutic molecules to construct 100-300 nm nano-assemblies.
Fig.1 Extended conformation of squalene. (Desmaële, 2012)
Squalene is well tolerated whether intravenously or orally. Since squalene is a biological source and is often used as a dietary supplement, squalene is a favorable susceptible substance from a toxicological point of view. Therefore, squalene has been widely used as a carrier/adjuvant for therapeutic applications.
Two cationic squalene derivatives (SQ+) were straightforwardly prepared from squalene either with a quaternary ammonium head group (SQ-NMe3+) or with a guanidinium head group (SQ-NH(NH2)C=NH2+). Nanoparticles were obtained by the nanoprecipitation procedure previously described for squalene derivatives. The squalene nanoparticles obtained by a simple nanoprecipitation procedure form very stable and reproducible nanoparticles. This new type of nanovector, made of one component, formed complexes with siRNAs and protected siRNAs from nucleases. These complexes allowed efficient delivery of siRNAs in cells where their interfering activity indeed occurred. This constitutes a new strategy for siRNA vectorization with promising applications for animal experiments or therapeutic developments.
Fig.2 Binding of siRNA on SQ-NMe3+ NPs (A) and on SQ-NH(NH2)C=NH2+ NPs (B). (Bertrand, 2015)
Squalene has so far been used as a drug carrier in either emulsions or squalene-drug conjugates. For instance, a squalene emulsion stabilized by phosph atidylethanolamine or pluronic F68 was shown to prolong in vitro release of a morphine prodrug. Administered intravenously in vivo, these prodrug-loaded squalene emulsion formulations exhibited prolonged analgesic activity in rats. Similar emulsions have been successfully employed to deliver lipophilic ester prodrugs of nalbuphine. In another report, a nanostructured lipid carrier based on squalene and precirol was shown to increase skin permeability and control delivery of the encapsulated psoralen (an anti-psoriatic medicine).
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