The Polar Lipid Fraction E from Sulfolobus acidocaldarius Can Be Used as Liposomal Drug Stabilizing Agents to Reduce the Leakage of the Antivascular Drug Combretastatin A4 Disodium Phosphate from Tetraether/Diester Hybrid Archaeosomes

Liposomes have many advantages as therapeutic capsules over free drugs such small molecule and nucleic acids. Cholesterol is commonly used a membrane stabilizing agent in liposomal (e.g., mRNA-lipid nanoparticle COVID-19 vaccines). However, due to the vulnerability of cholesterol oxidation etiological role disorders, it desirable find an alternative means stabilize membranes for drug delivery. In this study, we demonstrated that polar lipid fraction E (PLFE), which contains exclusively bipolar tetraether macrocyclic lipids, isolated from thermoacidophilic archaeon S. acidocaldarius can greatly formulation anti-vascular drug, combretastatin A4 disodium phosphate (CA4P). Stability was assessed by determining leakage rate constant k entrapped CA4P fluorometrically. We found that, at 37 °C, PLFE decreases value monotonically 1.54 × 10?2 s?1 100% 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine (POPC) liposomes 3.4 10?5 archaeosomes, change two orders magnitude. The changes are correlated well with CA4P’s cytotoxicity against MCF-7 breast cancer cells. further showed reduction spontaneous be attributed increased surface charge order packing tightness liposomes, reflected zeta potential (?6.83 ?41.1 mV 0 100 mol% PLFE) diphenylhexatriene (DPH) fluorescence polarization (0.13 0.4 measurements. Moreover, slows down more than POPC liposomes. These results together suggest lipids serve effective could potentially useful optimization treatment.