Preparation of Poly(ethylene Glycol)-Grafted Liposomes with Ligands at the Extremities of Polymer Chains

Zalipsky, Samuel; Mullah, Nasreen; Qazen, Masoud M.

doi:10.1016/s0076-6879(04)87004-6

Cited by 13 publications

(4 citation statements)

References 48 publications

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“…HPLC-grade methanol and chloroform were from Mallinckrodt (St. Louis, MO). PEG lipids (Figure B) were prepared as described previously. , The PEG tether MW in these experiments was 2000, 3300, or 6260 ( N = 44, 77, or 142 monomer units, respectively). , …”

Section: Methodsmentioning

confidence: 99%

“…An important role of the spacer is to enable the active domain of the CAM molecule to protrude through the cell's glycocalyx to access complementary binding domains on opposing surfaces. − The spatial and temporal specificity that is a hallmark of cellular adhesion arises from a combination of background, nonspecific steric repulsive forces due to the glycocalyx long-range sampling ability conferred by the flexible tether and short-range “lock-and-key” binding. Poly(ethylene glycol) (PEG) has been used extensively as a synthetic flexible spacer that mimics the glycocalyx and CAMs: the unmodified PEG acts as a steric stabilizer, , and adhesive groups (ligands) can be easily coupled to its terminal end . Although there have been numerous studies investigating the steric effects of PEG, a complete understanding of its unique behavior is still lacking.…”

Section: Introductionmentioning

confidence: 99%

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Dynamics of Membrane Adhesion: The Role of Polyethylene Glycol Spacers, Ligand−Receptor Bond Strength, and Rupture Pathway

Wong

Kuhl

2008

Langmuir

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Biological adhesion typically occurs through discrete cross bridges between complementary molecules on adjacent membranes. Here we report quantitative measurements of the binding distance between a lipid membrane functionalized with ligands on flexible polymer tether chains and a second membrane bearing complementary receptors using the surface force apparatus technique. The binding distance is shown to increase as a function of polymer tether length. Upon separation, adhesive failure occurs not at the strong ligand-receptor bond but primarily through the mechanical pullout of cross-bridging polymer tethers from the membrane. We summarize these measurements of complementary membrane adhesion dynamics using an energy-state diagram that encompasses the energetics of the polymer tether, ligand-receptor bond strength, and number of cross bridges formed.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Dynamics of Membrane Adhesion: The Role of Polyethylene Glycol Spacers, Ligand−Receptor Bond Strength, and Rupture Pathway

Wong

Kuhl

2008

Langmuir

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“…The thin lipid layer was then hydrated with 6 mL of phosphate buffer (pH = 7.4) and annealed for 1 h at 45 °C. To produce unilamellar vesicles [ 26 ], RIF liposomes were then extruded (Thermobarrel Extruder, Lipex Biomembranes, Inc., Vancouver, British Columbia, Canada) 10 times through two (0.1 µm, stacked) polycarbonate filters (Osmonics Inc., Livermore, CA, USA) at 170 psig with nitrogen gas. The final RIF concentration of the liposomal suspension was 10 mg/mL.…”

Section: Methodsmentioning

confidence: 99%

Efficacy of Combined Rifampicin Formulations Delivered by the Pulmonary Route to Treat Tuberculosis in the Guinea Pig Model

et al. 2021

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Liposomes, as vehicles alone or in combination with rifampicin (RIF) microparticles (RMs), were evaluated as vehicles to enhance the permeation of RIF into granulomas. RIF liposomes (RLs) were extruded through a 0.1 µm polypropylene membrane. RMs were prepared by the solvent evaporation method. Four weeks after infection, guinea pigs (GPs) were assigned to groups treated with a combination of RM-RLs or RLs alone. RLs were nebulized after extrusion whereas RMs were suspended in saline and nebulized to GPs in a nose-only inhalation chamber. Necropsy was performed after the treatment; the lungs and spleen were resected for bacteriology. RLs had mean diameters of 137.1 ± 33.7 nm whereas RMs had a projected area diameter of 2.48 µm. The volume diameter of RMs was 64 ± 1 µm, indicating that RMs were aggregated. The treatment of TB-infected GPs with RLs significantly reduced their lung bacterial burden and wet spleen weight compared with those treated with blank liposomes. The treatment of TB-infected animals with RM-RLs also reduced their lung bacterial burden and wet spleen weight even though these reductions were not statistically different. Based on these results, the permeation of RIF into granulomas appears to be enhanced when encapsulated into liposomes delivered by the pulmonary route.

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“…The lipids purchased from Avanti Polar Lipids (Alabaster, AL) include 1,2-Distearoyl-sn-Glycero-3-Phosphoethanolamine-N-z (mPEG2000-DSPE), 1,2-Distearoyl-sn-Glycero-3-Phosphoethanolamine-N-[Methoxy(Polyethylene glycol)-5000] (mPEG5000-DSPE), L-a-Phosphatidylcholine (eggPC) and 1,2-Dipalmitoyl-sn-Glycero-3-Phosphoethanolamine-N-(Cap Biotinyl) (biotin-DPPE). Biotin-PEG3350-DSPE is prepared as previously described (18,34). Thioctic acid-PEG3350-DSPE is prepared as described below.…”

Section: Methodsmentioning

confidence: 99%

Targeted binding of PLA microparticles with lipid-PEG-tethered ligands

et al. 2007

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Solid core polymeric particles are an attractive delivery vehicle as they can efficiently encapsulate drugs of different physical and chemical characteristics. However, the effective targeting of such particles for therapeutic purposes has been somewhat elusive. Here, we report novel polymeric particles comprised of poly(lactic acid) (PLA) with incorporated poly(ethylene glycol)-lipids (PEGlipids). Particles are characterized for morphology, surface charge, and composition with fieldemission scanning electron microscopy (FESEM), zeta potential measurements, and proton nuclear magnetic resonance ( 1 H NMR) spectroscopy respectively. The surface densities of PEG lipids determined by 1 H NMR and particle size distributions are consistent with scaling theory for adsorption of chains onto a surface. We observe significant binding of liganded PEG-lipid tethers when the molecular weight is greater than the unliganded PEG-lipids for significant binding events. Importantly, the binding is not completely lost when the unliganded PEG molecular weight is greater than the liganded PEG-lipid tether. We observe a similar trend for the lower affinity ligand (thioctic acid), but the degree of binding is significantly lower than the high affinity ligand (biotin). This novel technique used to fabricate these liganded particles combined with the lipid bilayer binding studies provides a platform for systematic optimization of particle binding.

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Preparation of Poly(ethylene Glycol)-Grafted Liposomes with Ligands at the Extremities of Polymer Chains

Cited by 13 publications

References 48 publications

Dynamics of Membrane Adhesion: The Role of Polyethylene Glycol Spacers, Ligand−Receptor Bond Strength, and Rupture Pathway

Dynamics of Membrane Adhesion: The Role of Polyethylene Glycol Spacers, Ligand−Receptor Bond Strength, and Rupture Pathway

Efficacy of Combined Rifampicin Formulations Delivered by the Pulmonary Route to Treat Tuberculosis in the Guinea Pig Model

Targeted binding of PLA microparticles with lipid-PEG-tethered ligands

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