Vaccine Lab / Alfa Chemistry
pH-Sensitive Lipids
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pH-Sensitive Lipids

The theory of pH-sensitive lipids emerged from the reality that certain enveloped viruses developed strategies to benefit from the acidification of the endosomal lumen to infect cells, as well as from the observation that some pathological tissues (tumors, inflamed and infected areas) exhibit an acidic environment as compared with normal tissues [1]. pH-sensitive lipids are stable at physiological pH (pH 7.4) but undergo destabilization, and acquire fusogenic properties under acidic conditions, thus leading to the release of their aqueous contents and their transport into the intracellular biological environment. The pH-sensitive lipids are being explored as promising vehicles for delivery of therapeutic and prophylactic vaccines. These lipids are employed as effective means for delivery of nucleic acids, producing efficient immune response and reducing their toxicity.

Mechanisms of intracellular delivery of pH-sensitive lipidsFigure 1. Mechanisms of intracellular delivery of pH-sensitive lipids; (1) Destabilization of pH-sensitive lipids triggers the pore formation in endosomal membrane, (2) Destabilization of lipids release the encapsulated molecules in endosome which diffuse to the cytoplasm through the endosomal membrane, (3) Fusion between the lipid and the endosomal membranes [2].

Composition of pH-sensitive lipids

The pH-sensitive lipids are mainly prepared with neutral cone-shaped lipid dioleoyl phosphatidylethanolamine (DOPE) and a weakly acidic amphiphile, such as cholesteryl hemisuccinate (CHEMS). The DOPE part has shown the polymorphic phase behavior such as their orientation is not a bilayer but a hexagonal in aqueous media and offered the fusogenic property. For stabilization of DOPE part in lipids, other negatively charged lipids are incorporated, namely dioleoyl phosphatidylcholine (DOPC) or N-succinyl- DOPE. These lipids were neutral in nature in the acidic environment of the endosome, leading to destabilization, fusion with endosomal membrane and release of their contents.

What we offer

pH-sensitive lipids have good prospects for application as nucleic acid delivery carriers. It has shown unique advantages in effectively reducing cytotoxicity, improving drug targeting, and enhancing therapeutic effects. Alfa Chemistry supplies PH-sensitive lipids to companies researching nucleic acid delivery systems. If you cannot find the PH-sensitive lipid you need, please contact us. We also offer product customization according to customer's detailed requirements.


  1. Torchilin, V. P.; et al. pH-sensitive liposomes. J. Liposome Res. 1993, 3: 201-255.
  2. Shivani, R. P.; et al. A review of mechanistic insight and application of pH-sensitive liposomes in drug delivery. Drug Delivery. 2015, 22: 231-242.

Our products and services are for research use only and cannot be used for any clinical purposes.

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