Cancer is one of the leading causes of death in the US. Drug delivery systems still face the challenge of selectively increasing the availability of drug at the target tissue, while maintaining stability during circulation. pH sensitive liposomes can be used to release their contents during endocytosis. This approach relies on selective destabilization of liposomal membrane following acidification of the surrounding medium, therefore exploiting the acidic environment of the endosomal pathway to trigger content release.

In this work we developed a novel pH-sensitive lipid-based drug carrier based on lamellar-forming lipids for triggered release of encapsulated therapeutic agents. For enhanced circulation time, high Tg lipids (>70⁰C) and lipids with anchored polyethylene glycol chains were used. We efficiently loaded doxorubicin on preformed liposomes. In addition, we studied the release of contents in serum supplemented media as a function of pH and time, and compared the content retention profiles to a DSPC-based liposome resembling the Dox® composition. Our results demonstrate that the proposed liposomes exhibit 80 % of content retention at physiological pH for the first 90 minutes and 35 % release of the encapsulated drug at pH 4.0 within the first one hour of incubation. The outcomes of this study indicate the potential in utilizing this newly developed pH-triggered liposome in delivering anticancer therapeutics.