PG-based Anionic-Liposomes

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Phosphatidylglycerol (PG) is one typical of universal phospholipids (1-2% of total phospholipids), contains two acyl chains ester with glycerol, which in turn is linked to a headgroup structure containing a net charge. PG contains a phosphate in its head group and no other group with compensating positive charges (the remaining structure is glycerol). As a result, PG has a net negative charge, which introduces the negative charge to the membrane surface and to the lipid-protein interface. As a common anionic molecule, PG can form liposomes with negative Zeta potential, whose varies depending on the molar percentage of negatively charged lipids in the liposome preparation. PG-based anionic liposomes display greater storage stability with lower aggregation in solution, compared with neutral charged liposomes. PG-based anionic liposomes remained stable at 2-8°C with no significant effect on drug absorption properties during short-term storage.


Phosphatidylglycerol (PG)-based liposomes are usually monolayers and 100 nm in size.

Their main components are 1,2-dioleoyl-sn-glycero-3-phospho-(1’-rac-glycerol) (DOPG) and 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC). They can be prepared in different molar ratios (DOPG:DOPC) depending on the desired lipid load.

Both DOPG and DOPC are unsaturated lipids with liquid-to-gel phase transition temperature below zero degrees Celsius, and unsaturated lipids have "curly legs", so they form loose liposomes. It is possible to influence the interaction of molecules with the liposome surface.

Composition of phosphatidylglycerol (PG)-based liposomesFig. 1 Composition of phosphatidylglycerol (PG)-based liposomes


The most widely used technique for the preparation of liposomes is the thin-film dehydration-rehydration method.

The process of thin-film dehydration-rehydration method Fig. 2 The process of thin-film dehydration-rehydration method

In this technique the drug to be embedded can be contained in a water-based medium (for hydrophilic drugs) or in a lipid membrane (for lipophilic drugs). Post-processing can ensure that liposomes manufactured using the above techniques have the desired size, lamination, and homogeneity. The most common methods for post-forming processing are ultrasonic treatment, extrusion, and high-pressure homogenization, and finally the liposomes should be stored at 4°C and used for further experiments within 2 weeks.


PG-based anionic liposome, a naturally occurring eukaryotic cell membrane component, have been shown to significantly improve gene transfection efficiency in cell lines, even better than commercial cationic liposomes, and have recently been explored as potential delivery vector for gene and vaccine and drugs.

Negatively charged liposomes diffuse through the cuticle and hair follicle to the dermis and lower part of the hair follicle much faster than positively charged liposomes. Therefore, rapid penetration of PG-based anionic liposomes would help increase drug penetration through the skin.

Antisense oligonucleotides (ONs) against p53 delivered by PG-based anionic liposomes for a short time prevented hippocampal neurons from glutamate-induced death through sequentially specific downregulation of p53 without any apparent toxicity. In addition, similar studies were performed in primary neurons, immortalized fibroblasts, and cell lines derived from liver, kidney, ovary, and cervix, and found that PG-based anionic liposomes can successfully deliver Cy3ON to the entire cell population within 1 hour, regardless of cell type.

PG also has a favorable effect on the resolution of inflammation, such as in infections with respiratory syncytial virus, mycoplasma pneumoniae, and influenza A virus, as well as on corneal epithelial wound and skin healing, and it may act as an anti-inflammatory agent to prevent allergic reactions to unrelated environmental antigens in the lower respiratory tract. As a consequence, PG-based anionic liposomes have promising potential to be exploited as excellent anti-inflammatory liposomes.


  1. Klein M.E.; et al. Towards the development of long circulating phosphatidylserine (PS)- and phosphatidylglycerol (PG)-enriched anti-inflammatory liposomes: is pegylation effective? Pharmaceutics. 2021. 13(2): p. 282.
  2. Bruzzese A; et al. Structural insights into positive and negative allosteric regulation of a G protein-coupled receptor through protein-lipid interactions. Sci Rep. 2018. 8(1): p. 4456.
  3. Bozzuto G; et al. Liposomes as nanomedical devices. Int J Nanomedicine. 2015. 10: p. 975-99.
  4. Benne N; et al. Atomic force microscopy measurements of anionic liposomes reveal the effect of liposomal rigidity on antigen-specific regulatory T cell responses. Journal of Controlled Release. 2020. 318: p. 246-255.
  5. Chen L; et al. Enhanced nasal mucosal delivery and immunogenicity of anti-caries DNA vaccine through incorporation of anionic liposomes in chitosan/DNA complexes. PLoS One. 2013. 8(8): p. e71953.

※ Only for research. Not suitable for any diagnostic or therapeutic use.

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