AI Article Synopsis
- The study focuses on creating pH-sensitive liposomes that release their cargo quickly when exposed to acidic environments, making them effective for targeted drug delivery where acidity is higher (like tumors).
- These liposomes are formed from a mixture of a specific amphiphile, a phospholipid, and a PEG-lipid conjugate, and they maintain stability for over a year at cooler temperatures while remaining effective in simulated body conditions.
- When tested, the drug-loaded liposomes showed a rapid release of their contents in low pH conditions and increased cytotoxicity against cancer cells compared to the free drug, suggesting their potential for better cancer treatment.
Article Abstract
Incorporation of a pH-sensitive conformational switch into a lipid structure enables a drastic conformational flip upon protonation that disrupts the liposome membrane and causes rapid release of cargo specifically in areas of increased acidity. pH-sensitive liposomes containing the amphiphile (1) with trans-2-morpholinocyclohexanol conformational switch, a phospholipid, and a PEG-lipid conjugate were constructed and characterized. The optimized composition-1/POPC/PEG-ceramide (50/45/5)-could be stored at 4 °C and pH 7.4 for up to 1.5 years, and was stable in blood serum in vitro after 48 h at 37 °C. Liposomes loaded with ANTS/DPX or methotrexate demonstrated an unusually quick content release (in a few seconds) at pH below 5.5, which was independent of inter-liposome contact. The pH-titration curve for the liposome leakage paralleled the curve for the acid-induced conformational flip of 1 studied by 1H-NMR. Freeze-fracture electron microscopy images showed budding and division of the bilayer at pH 5.5. A plausible mechanism of pH-sensitivity involves an acid-triggered conformational flip of 1, shortening of lipid tails, and membrane perturbations, which cause the content leakage. The methotrexate-loaded liposomes demonstrated much higher cytotoxicity in HeLa cells than the free drug indicating that they can serve as viable drug delivery systems.
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|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3857072 | PMC |
| http://dx.doi.org/10.3390/pharmaceutics3030379 | DOI Listing |
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