Change in the Character of Liposomes as a Drug Carrier by Modifying Various Polyethyleneglycol-Lipids

Abstract

When liposomes, as a superior drug carrier, are injected intravenously, active liposomes as medicines require polyethyleneglycol (PEG) as a modification tool around the liposomal membrane. PEG modification of a liposome forms a fixed aqueous layer, and the trapping by cells of the reticuloendothelial system (RES) is avoided. Hence, PEG-modified liposomes have long circulation in the bloodstream, and passive targeting to tumors has been achieved by PEG modification. We have been studying the passive targeting by liposomes with the expectation of more usefulness. It was proved a correlation between the PEG molecular weight of PEG-modified liposomes and blood circulation time and antitumor effect, too. Liposomes modified by PEG2000 were useful for uptake into tumor cells. We thought that the re-uptake in the liposomal membrane also increased accumulation. Moreover, it was proved that mixing two different PEGs to modify the liposome surface gives a bigger fixed aqueous layer thickness (FALT) around the liposome, giving the liposome strong antitumor activity. Then, we designed a novel PEG-lipid, 1,2-distearoyl-sn-glycero-3-phospho-ethanolamine-PEG (different double arms PEG; DDA-PEG), which had two different PEGs (2000 and 500) in one molecule. One of the innovative characteristics of DDA-PEG-modified liposome (DDAL) is that it heightens the contact ability with tumor cells. DDAL may be an effective DDS carrier for solving various PEG dilemmas. It was observed that passive targeting by PEG-modified liposomes had different characteristics by changing PEG length, anchor type or those combination. Thus, it should be applied to liposomes suitable for various diseases.

Surface Engineering of Liposomes for Stealth Behavior

“…In addition, liposomes modified with mixed PEGs having long, as well as short chains (PEG 2000 and PEG 500 ) demonstrate thicker FALT compared to that observed in the liposomes modified with a single PEG chain [48,49,50]. Interestingly, 1,2-distearoyl- sn -glycero-3-phosphoethanolamine-PEG 2 ( 2 ), having two different PEGs arms of MW 2000 and 500 Da in the same molecule, maintains a longer circulation time, with a larger FALT value and a higher contact ability with tumor cells compared to the liposomes PEGylated with regular PEG-lipids [47]. The steric stabilization afforded by PEG-phospholipids is also influenced by the size of the liposomes.…”

“…PEG modification forms a fixed aqueous layer thickness (FALT) around the surface of the liposome [46]. FALT increases with the increase in PEG MW, which positively correlates with the duration of the persistence of liposomes in circulation [47]. In addition, liposomes modified with mixed PEGs having long, as well as short chains (PEG 2000 and PEG 500 ) demonstrate thicker FALT compared to that observed in the liposomes modified with a single PEG chain [48,49,50].…”

“…Studies have shown that strong surface hydration increases the thickness of the fixed aqueous layer around the surface, which prevents interaction with protein [47,136]. All the polymers discussed so far bestow stealth property to liposomes mainly by enabling hydration through H-bonding.…”

Hybrid Nanogels: Stealth and Biocompatible Structures for Drug Delivery Applications

“…Another main effect is related to the high hydrophilicity acquired by the particle surface, less susceptible to antibody recognition [91]. This effect is even described as the formation of an aqueous layer that disguise the structure from the opsonization processes [92]. According to the ligand density and polymer sizes, the chains may assume different spatial dispositions (e.g., “mushroom” or “brush”).…”

Effect of Pegylation and Targeting Moieties on the Ultrasound-Mediated Drug Release from Liposomes

“…However, PEG with longer chains (higher molecular weight), e.g., PEG-2000, provides a shielding effect by forming a fixed aqueous layer thickness (FALT) surrounding the liposome. This layer increases with the increase in PEG molecular weight resulting in the higher stability and longer liposomal circulation time when injected into the bloodstream . To the best of our knowledge, there are no reports of detailed investigations on the effect of long-chain pegylation and the presence of targeting moieties on the ultrasound-mediated drug release from the liposomes.…”