High performance liquid chromatography analysis of 100-nm liposomal nanoparticles using polymer-coated, silica monolithic columns with aqueous mobile phase

Itoh, Naoki; Kimoto, Arato; Yamamoto, Eiichi; Higashi, Tatsuya; Santa, Tomofumi; Funatsu, Takashi; Kato, Masaru

doi:10.1016/j.chroma.2016.12.080

Cited by 25 publications

(12 citation statements)

References 36 publications

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“…26) It is appropriate that albumin fluorescence changed within 30 min, because it has been reported that corona was formed just after intravenous administration of the liposomal drug. 8,9) Therefore, it is important to evaluate doxorubicin release from DOXIL that formed corona, and fluorescence spectrometry is a useful technique for this evaluation.…”

Section: Resultsmentioning

confidence: 99%

“…Hence, many previous studies have been conducted to study the dynamics and efficacy of the protein-DOXIL complex. [7][8][9] However, popular analytical methods (ultracentrifugation, gel electrophoresis, and circular dichroism) are laborious and time-consuming. [10][11][12] The development of a simple and easy monitoring method for doxorubicin release in biosamples is strongly demanded.…”

Section: Introductionmentioning

confidence: 99%

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A Simple and Easy Method of Monitoring Doxorubicin Release from a Liposomal Drug Formulation in the Serum Using Fluorescence Spectroscopy

Watanabe

Murayama

Karasawa

et al. 2019

CHEMICAL & PHARMACEUTICAL BULLETIN

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Formulation of a drug as liposomes facilitates its delivery to the disease target. Rightly, liposomes are gaining popularity in the medical field. In order for the drug to show efficacy, release of the encapsulated drug from the liposome at the target site is required. However, the release is affected by the permeability of the lipid bilayer of the liposome, and it is important to examine the effect of the surrounding environment on the permeability. In this study, we showed the usefulness of fluorescence analysis, especially fluorescence fingerprint, for a rapid and simple monitoring of release of an encapsulated anticancer drug (doxorubicin) from its liposomal formulation (DOXIL). Our result indicated that the release is accelerated by the existence of membrane permeable ions, such as tris(hydroxymethyl)aminomethane, and blood proteins like albumin. Hence, monitoring of doxorubicin release by fluorescence analysis is useful for the efficacy evaluation of DOXIL in a biomimetic environment.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A Simple and Easy Method of Monitoring Doxorubicin Release from a Liposomal Drug Formulation in the Serum Using Fluorescence Spectroscopy

Watanabe

Murayama

Karasawa

et al. 2019

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…Separation of DOXIL and Doxorubicin Using the GMACoated Column We previously reported that a GMA-coated column successfully separated DOXIL and doxorubicin within 2 min under aqueous conditions, 11) and therefore, we selected the GMA-coated column for use in this study. As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…11) Monolithic silica gel (3 mm i.d.×30 mm long) having a through pore size of 2 µm, mesopore size of 18 nm, and surface area of 200 m 2 /g was obtained from GL Sciences Inc. (Tokyo, Japan). The monolithic silica gel was modified with a spacer, N-(3-triethoxysilylpropyl) methacrylamide that was prepared from a mixture of 3-aminopropyltriethoxysilane and triethylamine in toluene and addition of methacryloyl chloride in toluene dropwise under stirring for 0.5 h at 0°C.…”

Section: Methodsmentioning

confidence: 99%

Rapid Analysis of DOXIL Stability and Drug Release from DOXIL by HPLC Using a Glycidyl Methacrylate-Coated Monolithic Column

et al. 2017

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In recent years, nanomedicines have received growing attention in a range of medical applications, including selective drug delivery technology. In this context, the analysis of liposome stability and drug release from liposomes is of particular importance, as the efficacy of a nanomedicine is determined by the release of the encapsulated drug. We investigated the influence of the surrounding environment on the stability and release of the encapsulated drug (i.e., doxorubicin) from DOXIL. Thus, for the purpose of this study, we selected the liposomal anticancer drug, DOXIL, as a typical nanomedicine, and investigated the influence of the surrounding environment on release of doxorubicin from DOXIL. We found that two pathways existed for doxorubicin release, namely the collapse of DOXIL, and an increase in the permeability of the lipid bilayer. DOXIL collapse occurred upon the addition of high concentrations (>60%) of a methanol solution, while an increase in permeability occurred at temperatures above the phase transition temperature of the DOXIL lipid bilayer, under basic conditions, and in the presence of membrane-permeable bases (e.g., Tris). As DOXIL is particularly stable and limited collapse of DOXIL occurred under physiological conditions, it is expected that doxorubicin release within the body took place through permeability changes in the lipid bilayer of the DOXIL structure.

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“…Nevertheless, those methods imply a priori characterization of the stability of encapsulated drugs during analysis to ensure that leakage does not occur. Moreover, adsorption of nanoparticles to a conventional stationary phase often precludes hydrodynamic separations [21,22].…”

Section: Introductionmentioning

confidence: 99%

Insights on Ultrafiltration-Based Separation for the Purification and Quantification of Methotrexate in Nanocarriers

et al. 2020

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The evaluation of encapsulation efficiency is a regulatory requirement for the characterization of drug delivery systems. However, the difficulties in efficiently separating nanomedicines from the free drug may compromise the achievement of accurate determinations. Herein, ultrafiltration was exploited as a separative strategy towards the evaluation of methotrexate (MTX) encapsulation efficiency in nanostructured lipid carriers and polymeric nanoparticles. The effect of experimental conditions such as pH and the amount of surfactant present in the ultrafiltration media was addressed aiming at the selection of suitable conditions for the effective purification of nanocarriers. MTX-loaded nanoparticles were then submitted to ultrafiltration and the portions remaining in the upper compartment of the filtering device and in the ultrafiltrate were collected and analyzed by HPLC-UV using a reversed-phase (C18) monolithic column. A short centrifugation time (5 min) was suitable for establishing the amount of encapsulated MTX in nanostructured lipid carriers, based on the assumption that the free MTX concentration was the same in the upper compartment and in the ultrafiltrate. The defined conditions allowed the efficient separation of nanocarriers from the free drug, with recoveries of >85% even when nanoparticles were present in cell culture media and in pig skin surrogate from permeation assays.

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High performance liquid chromatography analysis of 100-nm liposomal nanoparticles using polymer-coated, silica monolithic columns with aqueous mobile phase

Cited by 25 publications

References 36 publications

A Simple and Easy Method of Monitoring Doxorubicin Release from a Liposomal Drug Formulation in the Serum Using Fluorescence Spectroscopy

A Simple and Easy Method of Monitoring Doxorubicin Release from a Liposomal Drug Formulation in the Serum Using Fluorescence Spectroscopy

Rapid Analysis of DOXIL Stability and Drug Release from DOXIL by HPLC Using a Glycidyl Methacrylate-Coated Monolithic Column

Insights on Ultrafiltration-Based Separation for the Purification and Quantification of Methotrexate in Nanocarriers

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