Impact of spontaneous liposome modification with phospholipid polymer-lipid conjugates on protein interactions

Abstract

Liposome surface coating has been studied to avoid the immunological responses caused by the complement system, and alternative materials to poly(ethylene glycol) (PEG) have been explored recently since the production of anti-PEG IgM antibodies has been found in humans. We previously reported a liposome coating with poly(2-methacryloyloxyethyl phosphorylcholine) (poly(MPC))-conjugated lipids (PMPC-lipids) and demonstrated its protective effect on blood protein interactions. Here, we attempted to modify the liposome surface by exogenously adding PMPC-lipids, which were spontaneously incorporated into the outer membrane via hydrophobic interactions. The polymerization degree of the PMPC segment was regulated from 10 to 100. The incorporated ratio of PMPC-lipid increased with a decrease in the degree of PMPC polymerization. Due to surface modification with PMPC-lipids, increase in the length of the PMPC-chain increased the size of the liposomes. The modified liposomes were kept stable for 14 d in terms of their size, polydispersity, and surface properties, where approximately 70% of PMPC-lipids were incorporated into the liposome surface. We demonstrated that liposome surface modification with PMPC-lipids can inhibit protein adsorption when exposed to serum, regardless of the degree of polymerization of PMPC. In addition, the PMPC-lipid modified surface was not recognized by the anti-PEG IgM antibody, whereas PEG-lipid was recognized by the antibody. Thus, we successfully fabricated an inert liposome surface via spontaneous modification with PMPC-lipids, where only the outer bilayer surface was modified. This technique can be available for full loading of water-soluble active pharmaceutical ingredient inside the modified liposome.

Regulation of the innate immune system by fragmented heparin-conjugated lipids on lipid bilayered membranes in vitro

“…This suggested that the liposomes could be modified via external modification, where liposome surfaces are modified by exogenously mixing fHep-lipids with liposomes. 41 The long-term stability of the modified liposomes was also monitored over a period of 90 days, and no changes in size (Fig. 4D), PDI (Fig.…”

Zwitterionic Polymer-Decorated Lipid Nanoparticles for mRNA Delivery in Mammalian Cells

“…56−58 Moreover, PMPC-LPs demonstrated no interaction with the anti-PEG IgM antibody. 54,59 Recently, Adler et activators regenerated by electron transfer for atom transfer radical polymerization (ARGET-ATRP) method and coated LPs with 1−10 mol % PMPC−lipids. 60 The presence of PMPC−lipids on LPs can significantly reduce protein adsorption in human plasma and blood and became more effective as the molecular weight and molar ratio of the PMPC−lipids increased.…”

“…PMPC coating onto the surface of LPs can effectively prevent the adsorption of human complement protein C3 (C3), a key protein in the complement system . When C3 binds to a surface, it can initiate complement activation through an alternative pathway and then triggers recognition by complement receptors present on phagocytic cells. − Moreover, PMPC-LPs demonstrated no interaction with the anti-PEG IgM antibody. , Recently, Adler et al. synthesized PMPC–lipid (C18) pairs using PMPC molecules of various polymerization degrees, including 10 (MPC10–lipid), 20 (MPC20–lipid), 50 (MPC50–lipid), and 100 (MPC100–lipid), via the activators regenerated by electron transfer for atom transfer radical polymerization (ARGET-ATRP) method and coated LPs with 1–10 mol % PMPC–lipids .…”