Physical characterization of liposomal drug formulations using multi-detector asymmetrical-flow field flow fractionation

Parot, Jérémie; Caputo, Fanny; Méhn, Dóra; Hackley, Vincent A.; Calzolai, Luigi

doi:10.1016/j.jconrel.2020.01.049

Cited by 53 publications

(35 citation statements)

References 33 publications

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“…Analytical solutions for the retention time with exponential decay of cross-flow rate are available [34], as well as numerical solutions for the more general cases [35], yet they are of difficult implementation and limited use for the experimentalist. Second, the latex standards normally required for size calibration to be fractionated using detergent-enriched eluents (common choices are 0.2% Novachem [36], 0.02% FL-70 [37], 0.1% SDS [38], or similar) to prevent their aggregation, but these conditions may not be suitable for the samples [39]. And lastly and most importantly, the information provided by the online lightscattering detector complements, rather than substitutes, the one obtained from the retention time, as it will be shown in the following sections.…”

Section: Principles Of Fffmentioning

confidence: 99%

“…When AF4 is preliminary to proteomic analysis, the preservation of the integrity of the corona is of paramount importance, in addition to respecting the conformation and properties of the proteins. The eluent needs to be chosen so as to match the incubation medium, devoid of the macromolecular fraction: for nanoparticles incubated in plasma or serum, PBS or phosphate buffers (PB) are standard choices for the eluent [39,182,183,189], while protein-free intestinal fluid is an option for orally administered drugs [190]. As mentioned above, fractionation carried out with sufficiently mild separation techniques may lead to the retrieval of the corona in its entirety, while harsher conditions would cause the most loosely bound proteins to be washed away.…”

Section: Corona Compositionmentioning

confidence: 99%

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Asymmetric flow field-flow fractionation as a multifunctional technique for the characterization of polymeric nanocarriers

Quattrini

Berrecoso

Crecente‐Campo

et al. 2021

Drug Deliv. and Transl. Res.

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The importance of polymeric nanocarriers in the field of drug delivery is ever-increasing, and the accurate characterization of their properties is paramount to understand and predict their behavior. Asymmetric flow field-flow fractionation (AF4) is a fractionation technique that has gained considerable attention for its gentle separation conditions, broad working range, and versatility. AF4 can be hyphenated to a plurality of concentration and size detectors, thus permitting the analysis of the multifunctionality of nanomaterials. Despite this potential, the practical information that can be retrieved by AF4 and its possible applications are still rather unfamiliar to the pharmaceutical scientist. This review was conceived as a primer that clearly states the “do’s and don’ts” about AF4 applied to the characterization of polymeric nanocarriers. Aside from size characterization, AF4 can be beneficial during formulation optimization, for drug loading and drug release determination and for the study of interactions among biomaterials. It will focus mainly on the advances made in the last 5 years, as well as indicating the problematics on the consensus, which have not been reached yet. Methodological recommendations for several case studies will be also included. Graphical abstract

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Section: Principles Of Fffmentioning

confidence: 99%

Section: Corona Compositionmentioning

confidence: 99%

Asymmetric flow field-flow fractionation as a multifunctional technique for the characterization of polymeric nanocarriers

Quattrini

Berrecoso

Crecente‐Campo

et al. 2021

Drug Deliv. and Transl. Res.

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“…For this study, commercially available, non-FDA-approved liposomal DOX nanoparticle alternatives Dox-NP Ⓡ and Doxoves TM were employed for chemotherapeutic evaluation. Dox-NP Ⓡ is a pegylated liposomal formulation of DOX with an approximate particle diameter of 135 nm and a drug-load concentration of 2.2 mg/mL [ 13 ]. Doxoves TM is also characteristically similar to Doxil Ⓡ , with an approximate particle diameter of 85 nm and drug encapsulation efficiency of >98% [ 12 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

Assessing Advantages and Drawbacks of Rapidly Generated Ultra-Large 3D Breast Cancer Spheroids: Studies with Chemotherapeutics and Nanoparticles

Holub

Huo

Patel

et al. 2020

IJMS

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Traditionally, two-dimensional (2D) monolayer cell culture models have been used to study in vitro conditions for their ease of use, simplicity and low cost. However, recently, three-dimensional (3D) cell culture models have been heavily investigated as they provide better physiological relevance for studying various disease behaviors, cellular activity and pharmaceutical interactions. Typically, small-sized tumor spheroid models (100–500 μm) are used to study various biological and physicochemical activities. Larger, millimetric spheroid models are becoming more desirable for simulating native tumor microenvironments (TMEs). Here, we assess the use of ultra-large spheroid models (~2000 μm) generated from scaffolds made from a nozzle-free, ultra-high resolution printer; these models are explored for assessing chemotherapeutic responses with molecular doxorubicin (DOX) and two analogues of DoxilⓇ (Dox-NPⓇ, DoxovesTM) on MDA-MB-231 and MCF-7 breast cancer cell lines. To provide a comparative baseline, small spheroid models (~500 μm) were developed using a self-aggregation method of MCF-7 breast cancer cell lines, and underwent similar drug treatments. Analysis of both large and small MCF-7 spheroids revealed that Dox-NP tends to have the highest level of inhibition, followed by molecular doxorubicin and then Doxoves. The experimental advantages and drawbacks of using these types of ultra-large spheroids for cancer research are discussed.

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“…Over the past years, both FFF and NTA have significantly grown in popularity for the analysis of complex biological samples including extracellular vesicles such as exosomes [ 23 , 24 , 25 , 26 , 27 , 28 , 29 ], and liposomes [ 4 , 30 , 31 , 32 , 33 ]. It was therefore just a matter of time until both technologies were coupled in order to combine the advantages of both worlds.…”

Section: Introductionmentioning

confidence: 99%

Fast and Purification-Free Characterization of Bio-Nanoparticles in Biological Media by Electrical Asymmetrical Flow Field-Flow Fractionation Hyphenated with Multi-Angle Light Scattering and Nanoparticle Tracking Analysis Detection

Drexel

Siupa²,

Carnell-Morris³

et al. 2020

Molecules

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Accurate physico-chemical characterization of exosomes and liposomes in biological media is challenging due to the inherent complexity of the sample matrix. An appropriate purification step can significantly reduce matrix interferences, and thus facilitate analysis of such demanding samples. Electrical Asymmetrical Flow Field-Flow Fractionation (EAF4) provides online sample purification while simultaneously enabling access to size and Zeta potential of sample constituents in the size range of approx. 1–1000 nm. Hyphenation of EAF4 with Multi-Angle Light Scattering (MALS) and Nanoparticle Tracking Analysis (NTA) detection adds high resolution size and number concentration information turning this setup into a powerful analytical platform for the comprehensive physico-chemical characterization of such challenging samples. We here present EAF4-MALS hyphenated with NTA for the analysis of liposomes and exosomes in complex, biological media. Coupling of the two systems was realized using a flow splitter to deliver the sample at an appropriate flow speed for the NTA measurement. After a proof-of-concept study using polystyrene nanoparticles, the combined setup was successfully applied to analyze liposomes and exosomes spiked into cell culture medium and rabbit serum, respectively. Obtained results highlight the benefits of the EAF4-MALS-NTA platform to study the behavior of these promising drug delivery vesicles under in vivo like conditions.

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Physical characterization of liposomal drug formulations using multi-detector asymmetrical-flow field flow fractionation

Cited by 53 publications

References 33 publications

Asymmetric flow field-flow fractionation as a multifunctional technique for the characterization of polymeric nanocarriers

Asymmetric flow field-flow fractionation as a multifunctional technique for the characterization of polymeric nanocarriers

Assessing Advantages and Drawbacks of Rapidly Generated Ultra-Large 3D Breast Cancer Spheroids: Studies with Chemotherapeutics and Nanoparticles

Fast and Purification-Free Characterization of Bio-Nanoparticles in Biological Media by Electrical Asymmetrical Flow Field-Flow Fractionation Hyphenated with Multi-Angle Light Scattering and Nanoparticle Tracking Analysis Detection

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