Study On A Novel Kind Of PH-sensitive Liposomes

The pH-sensitive liposomes are a novel kind of liposomes,which exploit the acidic environment of tumors and the even more acidic environment in endosomes to trigger the destabilization of liposomal membranes and release its entrapped drugs.As new drug carriers with fine application prospect,pH-sensitive liposomes can actively target tumor sites and efficiently release anticancer drugs into cancer cells,which is a great advantage over the conventional liposomes.In this thesis,a novel kind of pH-sensitive phospholipids was designed and synthesized,using pentaerythritol as their skeleton instead of glycerol.This kind of pH-sensitive phospholipids used multi-alkoxy substituted benzyl acetals as the pH-sensitive moiety.After we finished the synthesis of the pentaerythritol lipids,the pH-sensitive liposomes were prepared.Their liposomal properties were preliminarily investigated.Meanwhile,the relatively pH-insensitive counterpart was also synthesized and investigated as the negative control.All of these liposomes were assembled by the filming-rehydration method.To determine the pH sensitivity of the novel liposomes,the change of their sizes in different pH conditions was observed.Then the release dynamics of the liposomes encapsulated calcein was studied through testing the release of calcein in different pH buffers.The liposome was stable(almost no release over 24 h at pH 7.4)under normal physiological conditions.However,the calcein could release up to 35%at pH 5.0 after 7 h at 37? oscillation,showing that the designed liposome was obviously pH-sensitive.The subsequent cytotoxicity assay indicated that this kind of pentaerythritol lipids was low cytotoxic.Overall,we have designed and synthesized a highly pH-sensitive phospholipid with low cytotoxicity.The acid hydrolysis of the liposome is ripid and releases its payloads in a relatively short time.The application of the liposome on drug delivery systems is promising.