Effect of molecular weight in amphipathic polyethyleneglycol on prolonging the circulation time of large unilamellar liposomes.

Maruyama, Kazuo; Yuda, Tsutomu; Okamoto, Akiyoshi; Ishikura, Chiyoji; Kojima, Shuji; Iwatsuru, Motoharu

doi:10.1248/cpb.39.1620

Cited by 109 publications

(34 citation statements)

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“…Chemical modifi cation of pharmaceutical nanocarriers with certain synthetic polymers, such as PEG, is the approach most frequently used to impart in vivo longevity to drug carriers, as was fi rst suggested for liposomes. [45][46][47][48][49] Hydrophilic polymers have been shown to protect individual molecules and solid particulates from interaction with different solutes. The term " steric stabilization " has been introduced to describe the phenomenon of polymermediated protection.…”

Section: Role Of Nanocarrier Longevity In the Bloodmentioning

confidence: 99%

Targeted pharmaceutical nanocarriers for cancer therapy and imaging

Torchilin

2007

AAPS J

670

428

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Section: Role Of Nanocarrier Longevity In the Bloodmentioning

confidence: 99%

Targeted pharmaceutical nanocarriers for cancer therapy and imaging

Torchilin

2007

AAPS J

670

428

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“…Chemical modification of pharmaceutical nanocarriers with certain synthetic polymers, such as polyethylene glycol (PEG), is the most frequent way to impart the in vivo longevity to drug carriers, as was first suggested for liposomes (17)(18)(19)(20)(21). This polymer is nontoxic, non-immunogenic, nonantigenic, highly soluble in water, and FDA approved (22).…”

Section: Introductionmentioning

confidence: 99%

Optimization of PEGylation Conditions for BSA Nanoparticles Using Response Surface Methodology

et al. 2010

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Abstract. Chemical coupling of polyethylene glycol (PEG) to proteins or particles (PEGylation), prolongs their circulation half-life by greater than 50-fold, reduces their immunogenicity, and also promotes their accumulation in tumors due to enhanced permeability and retention effect. Herein, phase separation method was used to prepare bovine serum albumin (BSA) nanoparticles. PEGylation of BSA nanoparticles was performed by SPA activated mPEG through their free amino groups. Effect of process variables on PEGylation efficiency of BSA nanoparticles was investigated and optimized through response surface methodology with the amount of free amino groups as response. Optimum conditions was found to be 32.5 g/l of PEG concentration, PEG-nanoparticle incubation time of 10 min, incubation temperature of 27°C, and pH of 7 for 5 mg of BSA nanoparticles in 1 mL phosphate buffer. Analysis of data showed that PEG concentration had the most noticeable effect on the amount of PEGylated amino groups, but pH had the least. Mean diameter and zeta potential of PEGylated nanoparticles under these conditions were 217 nm and −14 mV, respectively. In conclusion, PEGylated nanoparticles demonstrated reduction of the negative surface charge compared to the non modified particles with the zeta potential of −31.7 mV. Drug release from PEGylated nanoparticles was almost slower than non-PEGylated ones, probably due to existence of a PEG layer around PEGylated particles which makes an extra resistance in opposition to drug diffusion.

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“…12 For a series of PEG derivatives (MW 120-5,000 Da) used in hydrogenated soybean phosphatidylcholine (HSPC):choles terol:poly(ethylene glycol)-distearoylphosphatidylethanolamine (PEG-DSPE) liposomes with a size of 100 nm, it was reported that PEG with a molecular weight of ,750 Da promoted blood clearance and PEG with a molecular weight of .1,000 Da did not further increase the residence time of the vehicles in the blood. [12][13][14][15] Maruyama et al reported that liposomes (200 nm diameter) with PEG1000 or PEG2000 led to higher blood levels compared to liposomes with PEG5000. 16 The liposome composition, including the lipids, PEG, and PEG-lipids, is likely to influence the performance of colloidal particles in the blood and the tissue distribution.…”

Section: Introductionmentioning

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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Effect of molecular weight in amphipathic polyethyleneglycol on prolonging the circulation time of large unilamellar liposomes.

Cited by 109 publications

References 0 publications

Targeted pharmaceutical nanocarriers for cancer therapy and imaging

Targeted pharmaceutical nanocarriers for cancer therapy and imaging

Optimization of PEGylation Conditions for BSA Nanoparticles Using Response Surface Methodology

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

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