Dataset Information

Application of Asymmetrical Flow Field-Flow Fractionation for Characterizing the Size and Drug Release Kinetics of Theranostic Lipid Nanovesicles.

ABSTRACT: Liposome size and in vitro release of the active substance belong to critical quality attributes of liposomal carriers. Here, we apply asymmetric flow field-flow fractionation (AF4) to characterize theranostic liposomes prepared by thin lipid film hydration/extrusion or microfluidics. The vesicles' size was derived from multi-angle laser light scattering following fractionation (AF4) and compared to sizes derived from dynamic light scattering measurements. Additionally, we adapted a previously developed AF4 method to study zinc phthalocyanine (ZnPc) release/transfer from theranostic liposomes. To this end, theranostic liposomes were incubated with large acceptor liposomes serving as a sink (mimicking biological sinks) and were subsequently separated by AF4. During incubation, ZnPc was transferred from donor to acceptor fraction until reaching equilibrium. The process followed first-order kinetics with half-lives between 119.5-277.3 min, depending on the formulation. The release mechanism was postulated to represent a combination of Fickian diffusion and liposome relaxation. The rate constant of the transfer was proportional to the liposome size and inversely proportional to the ZnPc/POPC molar ratio. Our results confirm the usefulness of AF4 based method to study in vitro release/transfer of lipophilic payload, which may be useful to estimate the unwanted loss of drug from the liposomal carrier in vivo.

SUBMITTER: Skupin-Mrugalska P

PROVIDER: S-EPMC8508677 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Liposomal formulations for the treatment of cancer and other diseases are the most common form of nanotechnology enabled pharmaceuticals (NEPs) submitted for market approval and in clinical application today. The accurate characterization of their physical-chemical properties is a key requirement; in particular, size, size distribution, shape, and physical-chemical stability are key among properties that regulators identify as critical quality attributes. Here we develop and validate an optimized method, based on multi-detector asymmetrical-flow field flow fractionation (MD-AF4) to accurately and reproducibly separate liposomal drug formulations into their component populations and to characterize their associated size and size distribution, whether monomodal or polymodal in nature. In addition, the results show that the method is suitable to measure liposomes in the presence of serum proteins and can yield information on the shape and physical stability of the structures. The optimized MD-AF4 based method has been validated across different instrument platforms, three laboratories, and multiple drug formulations following a comprehensive analysis of factors that influence the fractionation process and subsequent physical characterization. Interlaboratory reproducibility and intra-laboratory precision were evaluated, identifying sources of bias and establishing criteria for the acceptance of results. This method meets a documented high priority need in regulatory science as applied to NEPs such as Doxil and can be adapted to the measurement of other NEP forms (such as lipid nanoparticle therapeutics) with some modifications. Overall, this method will help speed up development of NEPS, and facilitate their regulatory review, ultimately leading to faster translation of innovative concepts from the bench to the clinic. Additionally, the approach used in this work (based on international collaboration between leading non-regulatory institutions) can be replicated to address other identified gaps in the analytical characterization of various classes of NEPs. Finally, a plan exists to pursue more extended interlaboratory validation studies to advance this method to a consensus international standard.

Project description:Cellulose nanocrystals (CNCs) are renewable, naturally derived polymeric nanomaterials receiving substantial attention for a wide range of potential applications. The recent availability of high quality reference materials will facilitate the development and validation of measurement methods needed to advance the scientific and commercial use of CNCs. In the present study, we demonstrate an optimized method to fractionate CNCs with narrow size dispersion based on asymmetrical-flow field-flow fractionation (AF4) coupled with on-line multi-angle light scattering (MALS), dynamic light scattering (DLS), and differential refractometry (dRI). A stable suspension of CNC (Certified Reference Material CNCD-1, National Research Council-Canada) in deionized water was prepared using a dispersion method provided by NRC and adopted from a protocol originally developed at the National Institute of Standards and Technology. The as-prepared material was initially characterized in batch mode to validate the NRC dispersion method. AF4 was then optimized for channel and cross flow, mobile phase composition, and injection volume, among other parameters. Additionally, suspensions containing (1.25-10) mg mL-1 CNC were injected directly into the dRI detector (off-line), yielding a dn/dc value of 0.148 ± 0.003 mL g-1. dRI was then used as an on-line mass sensitive detector to quantify recovery. Results show that maximum recovery (? 99%) was achieved under optimized conditions. The weight-averaged molar mass (Mw) was estimated at roughly 107 Da from a partial Zimm analysis. The optical radius of gyration, Rg, and the hydrodynamic radius, Rh, were measured during elution. The shape factor (Rg/Rh) ranged from 1.5 to 1.9 for the fractionated material, supporting an elongated or rod-like structure. To our knowledge, this is the first time that both the morphology and molar mass of CNCs have been directly measured for the full distribution of species. Finally, we developed and demonstrated a semi-preparatory fractionation method to separate CNCs at the milligram scale for off-line research and analysis.

Dataset Information

Application of Asymmetrical Flow Field-Flow Fractionation for Characterizing the Size and Drug Release Kinetics of Theranostic Lipid Nanovesicles.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets