The use of asymmetrical flow field-flow fractionation with on-line detection in the study of drug retention within liposomal nanocarriers and drug transfer kinetics

Hinna, Askell; Hupfeld, Stefan; Kuntsche, Judith; Brandl, Martin

doi:10.1016/j.jpba.2016.02.037

Cited by 22 publications

(22 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Direct determination of the encapsulated drug is more accurate, but not always feasible. In many cases, the role of AF4 is limited to the separation of the carrier from the free drug, while the quantification is performed offline with a complementary technique such as HPLC [128][129][130][131][132]. Albeit of most general applicability, this approach is dispersive and time-consuming because of such issues as the need for preconcentrating the fractions and possible sample loss.…”

Section: Choice Of the Detectormentioning

confidence: 99%

“…Drugs with strong chromophores, such as those used in photodynamic therapy, can be easily detected by UV absorption spectroscopy (UV/Vis) or fluorescence detection (FLD), even when encapsulated inside the nanocarriers [129,131,132]. The interference due to the anisotropic scattering could be a serious issue and should be evaluated by running samples of blank nanocarriers [133].…”

Section: Choice Of the Detectormentioning

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

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: Choice Of the Detectormentioning

confidence: 99%

Section: Choice Of the Detectormentioning

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.

View full text Add to dashboard Cite

show abstract

“…Previously, the characterization of polymersome scaffold and size has been carried out by different analytical tools (small angle neutron or X‐ray scattering, cryogenic transmission electron microscopy (cryo TEM), static and dynamic light scattering (DLS)) . However, access to full information on the loaded polymersomes, including membrane composition and density of polymersomes, is thoroughly facilitated by multiple‐detector asymmetrical flow field flow fractionation (AF4) but so far not fully exploited to investigate liposomes and polymersomes . Most reports focused only on their size distribution or encapsulation efficiency .…”

Section: Introductionmentioning

confidence: 99%

Toward Functional Synthetic Cells: In‐Depth Study of Nanoparticle and Enzyme Diffusion through a Cross‐Linked Polymersome Membrane

et al. 2019

View full text Add to dashboard Cite

Understanding the diffusion of nanoparticles through permeable membranes in cell mimics paves the way for the construction of more sophisticated synthetic protocells with control over the exchange of nanoparticles or biomacromolecules between different compartments. Nanoparticles postloading by swollen pH switchable polymersomes is investigated and nanoparticles locations at or within polymersome membrane and polymersome lumen are precisely determined. Validation of transmembrane diffusion properties is performed based on nanoparticles of different origin—gold, glycopolymer protein mimics, and the enzymes myoglobin and esterase—with dimensions between 5 and 15 nm. This process is compared with the in situ loading of nanoparticles during polymersome formation and analyzed by advanced multiple‐detector asymmetrical flow field‐flow fractionation (AF4). These experiments are supported by complementary i) release studies of protein mimics from polymersomes, ii) stability and cyclic pH switches test for in polymersome encapsulated myoglobin, and iii) cryogenic transmission electron microscopy studies on nanoparticles loaded polymersomes. Different locations (e.g., membrane and/or lumen) are identified for the uptake of each protein. The protein locations are extracted from the increasing scaling parameters and the decreasing apparent density of enzyme‐containing polymersomes as determined by AF4. Postloading demonstrates to be a valuable tool for the implementation of cell‐like functions in polymersomes.

show abstract

“…Recently, Hu et al evaluated the drug distribution across different NP size fractions by collecting AF4 fractions followed by offline HPLC analysis [36]. Hinna et al and Fraunhofer et al investigated the feasibility of coupling AF4 with online UV-Vis analysis to directly probe loading or transfer between liposomal and gelatin NPs, respectively [37][38][39][40]. However, a major limitation of UV-Vis detection is the interference from particle scattering [37,41], which restricts measurements to only NPs with high analyte entrapment and can make quantification infeasible for larger NPs (with high scattering intensities) with low drug loading [37].…”

Section: Introductionmentioning

confidence: 99%

“…Both detectors show that the high burst release of enrofloxacin is indeed eliminated in AF4, while the NPs and entrapped drug are retained in the channel for analysis. Although prior AF4 methods have utilized UV-Vis detection for entrapped drug quantification[37][38][39][40]52], here UV-Vis was not suitable to quantify enrofloxacin in the PLGA-Enro NPs because the UV absorbance attributable to the drug was low relative to the particle scattering (SI,…”

mentioning

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

The use of asymmetrical flow field-flow fractionation with on-line detection in the study of drug retention within liposomal nanocarriers and drug transfer kinetics

Cited by 22 publications

References 30 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

Toward Functional Synthetic Cells: In‐Depth Study of Nanoparticle and Enzyme Diffusion through a Cross‐Linked Polymersome Membrane

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

Contact Info

Product

Resources

About