Amphipathic polyethyleneglycols effectively prolong the circulation time of liposomes

Klibanov, Alexander L.; Maruyama, Kazuo; Torchilin, Vladimir P.; Huang, Leaf

doi:10.1016/0014-5793(90)81016-h

Cited by 1,876 publications

(1,003 citation statements)

References 12 publications

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“…The lipid composition and surface properties play an important role in the binding of biotinylated liposomes to avidin, in vivo blood circulation, and the targeting efficacy of liposomes [29][30][31][32]. In this study, we have used a simple formulation consisting of DPPC as the core lipid, DSPE-PEG2kBiotin as a linker, and NBD-cholesterol as a fluorophore, to investigate the binding efficiency and construction of the new vehicle.…”

Section: Introductionmentioning

confidence: 99%

Acoustically-active microbubbles conjugated to liposomes: Characterization of a proposed drug delivery vehicle

Kheirolomoom

Dayton

Lum

et al. 2007

Journal of Controlled Release

208

175

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A new acoustically-active delivery vehicle was developed by conjugating liposomes and microbubbles, using the high affinity interaction between avidin and biotin. Binding between microbubbles and liposomes each containing 5% DSPE-PEG2kBiotin was highly dependent on avidin concentration and observed above an avidin concentration of 10 nM. With an optimized avidin and liposome concentration, we measured and calculated as high as 1000 to 10,000 liposomes with average diameters of 200 and 100 nm, respectively, attached to each microbubble. Replacing avidin with neutravidin resulted in 3-fold higher binding, approaching the calculated saturation level. Highspeed photography of this new drug delivery vehicle demonstrated that the liposome-bearing microbubbles oscillate in response to an acoustic pulse similar to microbubble contrast agents. Additionally, microbubbles carrying liposomes could be spatially concentrated on a monolayer of PC-3 cells at the focal point of ultrasound beam. As a result of cell-vehicle contact, the liposomes fused with the cells and internalization of NBD-cholesterol occurred shortly after incubation at 37°C, with internalization of NBD-cholesterol substantially enhanced in the acoustic focus.

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Section: Introductionmentioning

confidence: 99%

Acoustically-active microbubbles conjugated to liposomes: Characterization of a proposed drug delivery vehicle

Kheirolomoom

Dayton

Lum

et al. 2007

Journal of Controlled Release

208

175

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“…PET imaging and biodistribution studies were performed with free [ 18 Liposomes are vesicles composed of one or more concentric phospholipid bi-layers and such vesicles have been widely investigated as possible drug carriers [1,2]. Prolonged blood circulation of the liposomes is achieved with the addition of a polyethylene glycol (PEG) coating, which efficiently minimizes their removal by macrophages of the reticuloendothelial system [3][4][5][6]. Liposomes with various target-specific ligands attached to their surface are being investigated for targeted drug delivery [1,2,7].…”

Section: Introductionmentioning

confidence: 99%

Long-circulating liposomes radiolabeled with [18F]fluorodipalmitin ([18F]FDP)

Mařı́k

Tartis

Zhang

et al. 2007

Nuclear Medicine and Biology

101

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Synthesis of a radiolabeled diglyceride 3-[ 18 F]fluorodipalmitoyl-1,2-glycerol ( 18 F-fluorodipalmitin, [ 18 F]FDP) and its potential as a reagent for radiolabeling long-circulating liposomes were investigated. The incorporation of 18 F into the lipid molecule was accomplished by nucleophilic substitution of p-toluenesolfonyl moiety with a decay corrected yield of 43 ± 10% (n = 12). Radiolabeled long-circulating PEG-coated liposomes were prepared using a mixture of DPPC, cholesterol, DSPE-PEG2000 (61:30:9) and [ 18 F]FDP with a decay corrected yield of 70 ± 8% (n = 4). PET imaging and biodistribution studies were performed with free [ 18 Liposomes are vesicles composed of one or more concentric phospholipid bi-layers and such vesicles have been widely investigated as possible drug carriers [1,2]. Prolonged blood circulation of the liposomes is achieved with the addition of a polyethylene glycol (PEG) coating, which efficiently minimizes their removal by macrophages of the reticuloendothelial system [3][4][5][6]. Liposomes with various target-specific ligands attached to their surface are being investigated for targeted drug delivery [1,2,7]. Liposomes labeled with radioisotopes such as 99m Tc, 186 Re, 67 Ga, 111 In, and 18 F were previously employed to study the biodistribution of different types of liposomes in various animal models using scintigraphy, SPECT and PET. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Materials and Methods GeneralThe solvents and chemicals were purchased from Aldrich (Milwaukee, WI). The 1 H and 13 C NMR spectra were recorded using a Bruker Avance 500 spectrometer and the chemical shifts are reported relative to TMS. Analytical reversed-phase HPLC was performed using a Phenomenex Jupiter 5μ C4 300A column ( . The size distribution of liposomes was determined using a particle size analyzer Nanotrac NPA150 purchased from Microtrac Inc. (North Largo, FL). The lipid concentration was determined using a Phospholipids B kit purchased from Wako Chemicals, Inc. (Richmond, VA). Synthesis of 3-tosyl-1,2-dipalmitoyl glycerol (2)The precursor 2 was prepared according to the previously published procedure [32] from 1,2-dipalmitoyl-sn-glycerol (1) and 4-toluenesulfonyl chloride. The crude product was subsequently purified by recrystalization from hexane. 1 mL). The content of the vial was dissolved in anhydrous acetonitrile (0.35 mL) and transferred into a suspension of 2 (5.5 mg) in anhydrous acetonitrile (0.5 mL). The reaction mixture was heated to 100 ºC for 20 minutes and allowed to cool to room temperature for 5 min...

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“…Liposomes containing either monosialoganglioside G M1 (Allen et al, 1989) or polyethylene glycol (PEG) derivatives (Blume and Cevc, 1990;Klibanov et al, 1990;Allen et al, 1991;Maruyama et al, 1992;Woodle and Lasic, 1992;Yuda et al, 1996) are not readily taken up by the macrophages in reticuloendothelial system (RES), and hence remain in the blood circulation for a relatively long period of time. Particularly, PEG-modified liposomes (PEG liposomes) have been utilized as a particulate carrier for anti-tumor therapy due to their long circulation time.…”

Section: Introductionmentioning

confidence: 99%

Albumin-conjugated PEG liposome enhances tumor distribution of liposomal doxorubicin in rats

Yokoe

Sakuragi

Yamamoto

et al. 2008

International Journal of Pharmaceutics

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To evaluate the effect of coupling of recombinant human serum albumin (rHSA) onto the surface of poly(ethylene glycol)-modified liposome (PEG liposome) on the in-vivo disposition characteristics of liposomal doxorubicin (DXR), the pharmacokinetics and tissue distribution of DXR were evaluated after intravenous administration of rHSA-modified PEG (rHSA/PEG) liposomal DXR into tumor-bearing rats.rHSA/PEG liposome prepared using a hetero-bifunctional cross-linker, N-succinimidyl 3-(2-pyridyldithio) propionate (SPDP), efficiently encapsulated DXR (over 95%). rHSA/PEG liposomal DXR showed longer blood-circulating property than PEG liposomal DXR and the hepatic and splenic clearances of rHSA/PEG liposomal DXR were significantly smaller than those of PEG liposomal DXR. It was also demonstrated that the disposition of DXR to the heart, one of the organs for DXR-related side-effects, was significantly smaller than free DXR. Furthermore, the tumor accumulation of rHSA/PEG liposomal DXR was significantly larger than that of PEG liposomal DXR. The "therapeutic index", a criterion for therapeutic outcome, for rHSA/PEG liposomal DXR was significantly higher than PEG liposomal DXR. These results clearly indicate that rHSA-conjugation onto the surface of PEG liposome would be a useful approach to increase the effectiveness and safety of PEG liposomal DXR.

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Amphipathic polyethyleneglycols effectively prolong the circulation time of liposomes

Cited by 1,876 publications

References 12 publications

Acoustically-active microbubbles conjugated to liposomes: Characterization of a proposed drug delivery vehicle

Acoustically-active microbubbles conjugated to liposomes: Characterization of a proposed drug delivery vehicle

Long-circulating liposomes radiolabeled with [18F]fluorodipalmitin ([18F]FDP)

Albumin-conjugated PEG liposome enhances tumor distribution of liposomal doxorubicin in rats

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