Triggered Solute Release from Prosurfactant Incorporated Liposomes

Abstract

Switchable surfactant (SS) triggered release of encapsulated solute from liposomes was investigated. A range of redox and pH head group sensitive SSs were synthesised and characterised. Redox triggered SSs were derived from the nicotinamide moiety while pH triggered SSs incorporated amidine and imidazoline functional groups. The prosurfactant (PS) form of the SSs were incorporated into 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) liposomes at ratios of up to 20 mol% for pH SSs and 15 mol% for redox SSs. The switching characteristics of the incorporated SSs were investigated. The pKa of the pH SSs decreased, and redox potential of the redox SSs increased, over their respective free forms suggesting stabilisation of the PS due to the non-polar nature of the bilayer. SS triggered release studies from liposomes using the fluorescent molecule carboxyfluorescein (CF) indicated that SS incorporation of 10% induced the most CF release with additional SS altering the membrane character and suppressing release. An amidine SS with a C14 alkyl tail length was found to induce the greatest CF release which was thought to be due to the optimal compromise between packing parameter and hydrophobicity. Compared to imidazoline and redox SS, amidine derived SS also induced greater amounts of CF release possibly due to the greater hydrophilicity of the head group causing ejection of the surfactant from the bilayer, which also causes the system to be irreversible. In contrast, the imidazoline SS remained in the bilayer due to its hydrophobicity, and repeated triggering of the system induced CF release. Despite the greater pKa of the amidine compared to the imidazoline head group CF release was observed between similar pH ranges of between 9.0 and 7.0 when the pH of the system was decreased incrementally from pH 12.4. Of the redox SSs, only one was able to be effectively triggered, and was observed to induce significant CF release upon the addition of a molecular oxidant at elevated temperatures (25-30 °C). This was attributed to increased hydrogen bonding through the amide of the head group which stabilised the membrane. CO2(g) was demonstrated as an alternative trigger for pH SS incorporated liposomes. Where sparging with CO2(g) decreased the pH of the systems, triggering CF release. The imidazoline switched system was found to be reversible when the CO2 was displaced with argon. A coupled triggering mechanism was demonstrated with the incorporation of a photoacid generator (PAG) as a secondary trigger in imidazoline-liposomes. Upon irradiation with light the PAG generated acid which proceeded to protonate the PS, inducing CF release. By employing this method pH SS induced CF release was demonstrated at constant pH.