Grafted poly-(ethylene glycol) on lipid surfaces inhibits protein adsorption and cell adhesion

Abstract

Monolayers of dipalmitoyl-phosphatidylethanolamine (DPPE) mixing with various mole percentages of distearoyl-phosphatidylethanolamine (DSPE)-conjugated poly-(ethylene glycol) (PEG m.w. 750-5000) were deposited on DPPE-coated glass surfaces by the Langmuir-Blodgett method. Increasing percentages of grafted PEG in these supported lipid surfaces increasingly inhibit the adsorption of bovine serum albumin (BSA), laminin, and fibronectin. Increasing percentages of grafted PEG also inhibit the adhesion of erythrocytes, lymphocytes, and macrophages to these supported lipid surfaces. The adsorption of proteins on lipid coated glass surfaces were assayed by the fluorescence of FITC-labelled proteins. Cell adhesion was measured mainly by microscopic counting. The concentration of PEG-grafted lipids required for the inhibition of erythrocyte adhesion decreases with increasing molecular weight of the grafted PEG. The inhibitory effects are strongly dependent on the graft density of PEG at low concentrations, but weakly dependent on graft density at higher concentrations. For DSPE-PEG5000, the change of graft density dependency occurs approximately at the complete coverage of the lipid surface by the grafted polymer in the mushroom conformation (0.7 mol%), and the transition to partial brush conformation. The change-overs become less distinctive for grafted PEG of lower molecular weights, probably due to the failure of strictly mushroom and brush models of the polymer. The relative inhibitory efficiency is protein or cell dependent. The implication on the function of stealth liposomes is discussed.

Biocompatible micellar nanovectors achieve efficient gene transfer to vascular lesions without cytotoxicity and thrombus formation

“…[25][26][27] There are previous reports that the surface modification of biomaterials with PEG appreciably reduces thrombogenicity. 25,[28][29][30][31][32] Thus, it is widely accepted that PEG shields the cationic surface of biomaterials, reducing their thrombogenicity. 31 In this study, the PEG-b-P[Asp(DET)] micelle system showed no agglomeration even in the presence of blood components including serum albumin (Table 1 and Figure 4), platelets ( Figure 5) and erythrocytes ( Figure 6), whereas BPEI and P[Asp(DET)] polyplexes definitely showed the aggregate formation due to their positively charged character under the same conditions.…”

“…25,[28][29][30][31][32] Thus, it is widely accepted that PEG shields the cationic surface of biomaterials, reducing their thrombogenicity. 31 In this study, the PEG-b-P[Asp(DET)] micelle system showed no agglomeration even in the presence of blood components including serum albumin (Table 1 and Figure 4), platelets ( Figure 5) and erythrocytes ( Figure 6), whereas BPEI and P[Asp(DET)] polyplexes definitely showed the aggregate formation due to their positively charged character under the same conditions. It should be noted that PEG-b-P[Asp(DET)] micelle showed no platelet and erythrocyte aggregation even at a high N/P ratios, whereas P[Asp(DET)] and BPEI polyplexes induced platelet and erythrocyte aggregation even at low N/P ratios, such as 5.…”

Therapeutic applications of low-toxicity spherical nanocarbon materials

“…Therefore, these molecules have been used to physically modify the surfaces of SWNHs, thereby reducing non-specific binding onto SWNH aggregates. 96,97 Different types of PEG-based macromolecules showed different dispersion abilities with the SWNH aggregates. 98 When PEG-doxorubicin was used to disperse SWNH aggregates, the as-obtained conjugates induced the apoptosis of cancer cells due to the anticancer pharmacodynamics of doxorubicin.…”

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

“…15,18,19) With the increase of concentration of PEG-lipid on the liposomal membrane, serum protein prevents binding to the liposome membrane because of PEG-lipids overlapping each other. [20][21][22] As a result, it is considered that PEG-modified liposomes have a long circulation time. 8,9) However, the amount of PEG-lipids inserted into the liposome membranes is limited, and FALT forming around the liposomes reaches a plateau, 23) so it was considered that increasing FALT was difficult.…”