Comparative studies of polyethylene glycol-modified liposomes prepared using different PEG-modification methods

Nakamura, Koji; Yamashita, Keiko; Itoh, Yuki; Yoshino, Katsumi; Nozawa, Shigenori; Kasukawa, Hiroaki

doi:10.1016/j.bbamem.2012.06.019

Cited by 104 publications

(106 citation statements)

References 36 publications

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“…[16][17][18][19][20] The issue of micelle contamination and controlling the orientation of the anchors are major impediments to such an evaluation. Currently, three methods are in widespread use for modifying the liposomal surface.…”

Section: -9)mentioning

confidence: 99%

Topology of Surface Ligands on Liposomes: Characterization Based on the Terms, Incorporation Ratio, Surface Anchor Density, and Reaction Yield

Lee

Sato

Hyodo

et al. 2016

Biological & Pharmaceutical Bulletin

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The surface topology of ligands on liposomes is an important factor in active targeting in drug delivery systems. Accurately evaluating the density of anchors and bioactive functional ligands on a liposomal surface is critical for ensuring the efficient delivery of liposomes. For evaluating surface ligand density, it is necessary to clarify that on the ligand-modified liposomal surfaces, some anchors are attached to ligands but some are not. To distinguish between these situations, a key parameter, surface anchor density, was introduced to specify amount of total anchors on the liposomal surface. Second, the parameter reaction yield was introduced to identify the amount of ligand-attached anchors among total anchors, since the conjugation efficiency is not always the same nor 100%. Combining these independent parameters, we derived: incorporation ratio surface anchor density reaction yield. The term incorporation ratio defines the surface ligand density. Since the surface anchor density represents the density of polyethylene glycol (PEG) on the surfaces in most cases, it also determines liposomal function. It is possible to accurately characterize various PEG and ligand densities and to define the surface topologies. In conclusion, this quantitative methodology can standardize the liposome preparation process and qualify the modified liposomal surfaces.Key words active targeting; surface ligand density; incorporation ratio; surface anchor density; reaction yield; surface topology Nanotechnology has the capability to deliver drugs to specific cell types, but it is important to maximize therapeutic effects and minimize unexpected adverse effects, for this technology to be effectively used.1-4) In using nanoparticles for specific drug delivery, they need to have both a stealth function to prevent non-specific recognition by the reticuloendothelial system (RES), 5,6) and an active targeting function to allow them to bind to the specific cell type of interest. 7-9)Polyethylene glycol (PEG) modification is frequently used to confer a stealth function to nanoparticles. 5,6,10) For active targeting, specific ligands for bioactive molecules such as nucleic acids, peptides, proteins, and antibodies are attached to the surface of nanoparticles via a PEG spacer.11) Many attempts have been made to develop various types of specific ligands for use in active targeting, which is critical for targeting non-fenestrated tissues such as the brain, lung and related tissues. [12][13][14] The procedures used to prepare ligands that are used in modifying nanoparticles are relatively complicated because this increases the number of steps in the preparation process that can lead to conditions where ligand molecules can be unstable.15) Therefore, optimal reaction (modification) conditions and methods for quantifying the density of the attached ligand that is attached to the nanoparticles need to be evaluated precisely.Problems are usually encountered in evaluating both the density of the liposomal ligands and the PEG, since a variety of m...

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Section: -9)mentioning

confidence: 99%

Topology of Surface Ligands on Liposomes: Characterization Based on the Terms, Incorporation Ratio, Surface Anchor Density, and Reaction Yield

Lee

Sato

Hyodo

et al. 2016

Biological & Pharmaceutical Bulletin

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“…Furthermore, in addition to providing the hydrophilic surface required for lymphatic uptake, PEGylation also reduces the electrostatic interaction between the surface of the colloid and the components of the interstitial matrix by providing a neutral charge, which assists its drainage into the lymphatics. Thus, PEGylation has a positive impact not only in providing stealth attributes to colloids in blood [23][24][25][26] but also in facilitating their drainage from the site of injection to the lymphatics.…”

Section: Pegylation: Gateway For Lymphatic Targetingmentioning

confidence: 99%

“…Interestingly, inhibiting phagocytosis using dextran as an adjuvant increased both lymphatic uptake and residence time of PEGylated colloids. 21 PEGylation can be applied in developing various nanoparticulate carriers like dendrimers, 10 PRINT (particle replication in nonwetting templates) hydrogels, 28 magnetic carbon nanotubes with PEG groups, 29 solid lipid nanoparticles, 3 polymeric nanoparticles, 24 liposomes, 25 and so on. Furthermore, a glance at a few of the promising nanopharmaceuticals in clinical use or undergoing trials like Oncaspar (PEGylated l-asperginase for acute lymphoblastic leukemia), Genexol (PEGylated block polymer containing an anticancer drug for metastatic breast cancer), and Lipo-dox and ThermoDox (PEGylated liposomal forms of doxorubicin) highlights the utility of PEGylation.…”

Section: Pegylation: Gateway For Lymphatic Targetingmentioning

confidence: 99%

A brief perspective on the diverging theories of lymphatic targeting with colloids

Karthik

Marslin

Raghavan

et al. 2016

IJN

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For targeted delivery of colloids to the lymphatic system, the colloids should efficiently reach and remain in the lymphatics for a considerable period of time. As per the current knowledge, diffusion and phagocytosis are the two mechanisms through which colloids reach the lymphatic system. Several parameters including particle size and charge have been shown to affect the direct uptake of colloids by the lymphatic system. Although many researchers attached ligands on the surface of colloids to promote phagocytosis-mediated lymphatic delivery, another school of thought suggests avoidance of phagocytosis by use of carriers like polyethylene glycol (PEG)ylated colloids to impart stealth attributes and evade phagocytosis. In this perspective, we weigh up the paradoxical theories and approaches available in the literature to draw conclusions on the conditions favorable for achieving efficient lymphatic targeting of colloids.

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“…This negative charge rises from the incorporation of PEG-DSPE, which is considered to also be influenced by the shielding effect of the hydrophilic PEG moiety. 43 The size and zeta potential increased from 110.5 nm to 140.9 nm and from −1.4 mV to 18.4 mV, respectively, for the uncoated HSPC liposomes (the HSPC formulation) compared to chitosan-coated liposomes (the chitosan formulation). The EE% was determined by HPLC.…”

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confidence: 99%

The influence of different long-circulating materials on the pharmacokinetics of liposomal vincristine sulfate

Zhang

Chen

Li³

et al. 2016

IJN

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Purpose This study was designed to improve the in vivo pharmacokinetics of long-circulating vincristine sulfate (VS)-loaded liposomes; three different long-circulating materials, chitosan, poly(ethylene glycol)-1,2-distearoyl sn-glycero-3-phosphatidylethanolamine (PEG-DSPE), and poly(ethylene glycol)-poly-lactide- co -glycolide (PEG-PLGA), were evaluated at the same coating molar ratio with the commercial product Marqibo ® (vincristine sulfate liposome injection [VSLI]). Materials and methods VS-loaded liposomes were prepared by a pH gradient method and were then coated with chitosan, PEG-DSPE, or PEG-PLGA. Physicochemical properties, including the morphology, particle size, zeta potential, encapsulation efficiency (EE%), pH, drug loading, and in vitro release, were determined. Preservation stability and pharmacokinetic studies were performed to compare the membrane-coated liposomes with either commercially available liposomes or the VS solution. Results The sphere-like morphology of the vesicles was confirmed by transmission electron microscope. Increased particle size, especially for the chitosan formulation, was observed after the coating process. However, the EE% was ~99.0% with drug loading at 2.0 mg/mL, which did not change after the coating process. The coating of long-circulation materials, except for chitosan, resulted in negatively charged and stable vesicles at physiological pH. The near-zero zeta potential exhibited by the PEG-DSPE formulation leads to a longer circulation lifetime and improved absorption for VS, when compared with the PEG-PLGA formulation. Compared with the commercial product, PEG was responsible for a higher plasma VS concentration and a longer half-life. Conclusion PEG-DSPE coating may be related to better absorption, based on the stability and a pharmacokinetic improvement in the blood circulation time.

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Comparative studies of polyethylene glycol-modified liposomes prepared using different PEG-modification methods

Cited by 104 publications

References 36 publications

Topology of Surface Ligands on Liposomes: Characterization Based on the Terms, Incorporation Ratio, Surface Anchor Density, and Reaction Yield

Topology of Surface Ligands on Liposomes: Characterization Based on the Terms, Incorporation Ratio, Surface Anchor Density, and Reaction Yield

A brief perspective on the diverging theories of lymphatic targeting with colloids

The influence of different long-circulating materials on the pharmacokinetics of liposomal vincristine sulfate

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