Quantitative In Vitro Assessment of Liposome Stability and Drug Transfer Employing Asymmetrical Flow Field-Flow Fractionation (AF4)

Holzschuh, Stephan; Kaeß, Kathrin; Fahr, Alfred; Decker, Christiane

doi:10.1007/s11095-015-1831-y

Cited by 23 publications

(17 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Detergents [163] or other suitable reagents such as imidazole [165] can be added to prevent non-specific interactions with the channel walls or the membrane. The identity of the proteins can be guessed by studying their size and shape factor as determined by online MALS [165] or by running protein standards [163,164] or, for greater accuracy, by adding a selective stain [168] or by performing HPLC-MS analyses offline [167]. The proteins with which the drug interacts can be identified by downstream analyses of the collected fractions.…”

Section: Drug Transfer To Plasma Proteinsmentioning

confidence: 99%

“…More sophisticated analyses can be carried out on the appropriate systems. Liposomes incubated in plasma can rapidly transfer lipophilic drugs such as temoporfin to lipoproteins, and in a series of works [168,171] AF4 was employed to investigate the mechanism of said transfer: whether it happens through direct diffusion from the liposomes to the lipoproteins adsorbed on the vesicle surface, or because the vesicles membrane disintegrates. A lipid radiolabel was added to the temoporfin-loaded liposomes.…”

Section: Drug Transfer To Plasma Proteinsmentioning

confidence: 99%

“…Low-density and very-low density lipoproteins, though, have a size comparable to most of the nanoparticles used in drug delivery. This can be particularly serious for apolipoproteins, as they are known to be present in the corona of most polymeric nanoparticles [168]. Further interference can be due to aggregates of smaller proteins, both originated by the freeze-thawing of plasma samples and naturally present.…”

Section: Corona Compositionmentioning

confidence: 99%

See 2 more Smart Citations

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.

View full text Add to dashboard Cite

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

show abstract

Section: Drug Transfer To Plasma Proteinsmentioning

confidence: 99%

Section: Drug Transfer To Plasma Proteinsmentioning

confidence: 99%

Section: Corona Compositionmentioning

confidence: 99%

See 1 more Smart Citation

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.

View full text Add to dashboard Cite

show abstract

“…Optimization of the duration and flow rates of each step in the AF4 method typically revolves around achieving good size separation (by adjusting the focus flow rate or duration to focus the NPs into a narrow band against the accumulation wall and adjusting the crossflow rate in the elution step to achieve good resolution of different NP sizes) and good overall recovery with minimal perturbation of the NPs (for example, deformation of fragile NPs) [16]. However, for entrapped drug quantification, the potential for drug washout from the NPs during the focus step must also be considered [18,57,58]. Here, three focus flow rates (0.5 mL/min, 1.5 mL/min, and 2.0 mL/min) and two focus durations (4 min and 8 min) were compared (SI, Figure S2).…”

Section: Methods Development For Separation and Evaluation Of Plga-enro Nps By Af4-fldmentioning

confidence: 99%

Asymmetric Flow Field-Flow Fractionation (AF4) with Fluorescence Detection for Direct, Real-Time, Size-Resolved Measurements of Drug Release from Polymeric Nanoparticles

Shakiba¹,

Astete²,

Cueto³

et al. 2020

Preprint

View full text Add to dashboard Cite

Polymeric nanoparticles (NPs) are typically designed to enhance the efficiency of drug delivery by controlling the drug release rate. Hence, it is critical to obtain an accurate drug release profile. This study presents the first application of asymmetric flow field-flow fractionation (AF4) with fluorescence detection (FLD) to characterize release profiles of fluorescent drugs from polymeric NPs, specifically poly lactic-co-glycolic acid NPs loaded with enrofloxacin (PLGA-Enro NPs). In contrast to traditional release measurements requiring separation of entrapped and dissolved drugs (typically by dialysis) prior to quantification, AF4-FLD provides in situ purification of the NPs from unincorporated drugs, along with direct measurement of the entrapped drug. Size distributions and shape factors are simultaneously obtained by online dynamic and multi-angle light scattering detectors. The AF4-FLD and dialysis approaches were compared to evaluate drug release from PLGA-Enro NPs containing a high proportion (≈ 88%) of unincorporated (burst release) drug at three different temperatures spanning the glass transition temperature (30 °C for PLGA-Enro NPs). The AF4-FLD analysis was able to identify size-dependent release rates across the entire continuous NP size distribution, with smaller NPs showing faster release. The AF4-FLD method also clearly captured the expected temperature dependence of the drug release (from almost no release at 20 °C to rapid release at 37 °C). In contrast, dialysis was not able to distinguish these differences in the extent or rate of release of the entrapped drug because of interferences from the burst release background, as well as the dialysis lag time. A mechanistic diffusion model that integrates data from both AF4-FLD and dialysis further supported the advantages of AF4-FLD to capture the true release rate of entrapped drug and avoid artifacts observed in dialysis. Overall, this study demonstrates the novel application and unique advantages of AF4-FLD methods to obtain direct, size-resolved release profiles of fluorescent drugs from polymeric NPs.

show abstract

“…Direct chemical reactivity between lipids and the molecules that partition into membranes is very rarely considered. The chemical reactivity that is well described extends only to hydrolysis reactions involving bulk solvent (1)(2)(3) and autoxidation reactions (4-6), neither of which directly includes molecules that associate with membranes as part of their normal activity. In the eyes of many, lipid membranes, then, represent a stable environment into which molecules bind or insert as part of their normal function.…”

Section: Introductionmentioning

confidence: 99%

Lysis of membrane lipids promoted by small organic molecules: Reactivity depends on structure but not lipophilicity

et al. 2020

View full text Add to dashboard Cite

Several organic molecules of low molecular weight (<150 Da) are demonstrated to have substantial membrane-lytic potential despite having a low predicted lipophilicity (logD < 1 at neutral pH). In aqueous liposome dispersions, 38 aromatic compounds were tested for their ability to either promote lipid hydrolysis or directly participate in chemical reactions with lipid molecules. Behaviors observed included acyl transfer from the lipid to form a lipidated compound, both with and without concomitant lysolipid formation; increases in the rate of lipid hydrolysis without lipidation; and no reactivity. The variation in activity, including a notably higher activity for heterocycles such as amino-substituted benzimidazoles and indazoles, demonstrates the potential to predict or “design-in” lytic activity once the rules that govern reactivity are better understood. The nature of this chemical instability has significant ramifications for the use or presence of lipids in diverse fields such as materials chemistry, food chemistry, and cell physiology.

show abstract

Quantitative In Vitro Assessment of Liposome Stability and Drug Transfer Employing Asymmetrical Flow Field-Flow Fractionation (AF4)

Cited by 23 publications

References 48 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

Asymmetric Flow Field-Flow Fractionation (AF4) with Fluorescence Detection for Direct, Real-Time, Size-Resolved Measurements of Drug Release from Polymeric Nanoparticles

Lysis of membrane lipids promoted by small organic molecules: Reactivity depends on structure but not lipophilicity

Contact Info

Product

Resources

About