Neutral Liposomes
The materials of the neutral liposomes (Table 1) including natural product phosphatidylcholine (PC), phosphatidyl ethanolamine (PE) and synthetic product 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC). The non-charged lipids can also be referred to as helper lipids, which can stabilize the bilayer membrane and reduce the toxicity of the charged lipid component, wherein DOPE and cholesterol are most used. The role of cholesterol has been described above, the addition of DOPE can interfere with the lipid membrane, make the inclusion body unstable, promote the release of nucleic acid substances, and play an auxiliary role in cell osmosis.
Neutral liposomes can be transformed into lipids with different charges by modifying lipid molecules with different charges. Furthermore, in targeted tumor delivery, neutral liposomes play an advantage in EPR effect, and play a priority role in the treatment of solid tumors [47]. In immunization, using neutral liposome can induce a Th1 type immune response than cationic liposomes in the mice model [48]. In delivery, a neutral liposome loaded with focal adhesion kinase short interference RNA (FAKsiRNA) to treat ovarian cancer. The Western blotting and immunohistochemical analysis showed that a single dose of FAKsiRNA-liposome could effectively reduce the expression of FAK in vivo for up to 4 days, and the average tumor weight decreased significantly (44%-72%) [49]. In another cervical cancer treatment study, the stability, cytotoxicity, and cell uptake of targeted delivery of arsenic trioxide (ATO) to cervical cancer cells by liposomes of different charge types were investigated. The authors concluded that neutral liposomes prepared from PC and cholesterol selectively produced a high mortality rate in HeLa cells and minimal toxicity in control cells. Although ATO encapsulated by liposomes is less easily absorbed by cells than free ATO, delivered ATO can reduce the expression of oncogenes and show reduced toxicity [50].