Comparative Study on the Suitability of Two Techniques for Measuring the Transfer of Lipophilic Drug Models from Lipid Nanoparticles to Lipophilic Acceptors

Abstract

Abstract. Due to their particle size in the submicrometer range, lipid nanoparticles are suitable for parenteral administration. In order to obtain information on their potential in vivo performance, a simple and effective in vitro assay to evaluate the drug release behavior of such particles is required. This study compares the use of different experimental setups for this purpose. Lipid nanoparticles from trimyristin which were loaded with fluorescent lipophilic drug models (a temoporfin and Nile red) were used as donor particles. The transfer of the two drug models to multilamellar vesicles (MLV) and emulsion droplets as lipophilic acceptor compartments was examined. The determination of the transferred substance was performed either after separation by centrifugation or by an in situ flow cytometric technique. The transfer of temoporfin was slow to the acceptor MLV and very rapid to the acceptor emulsion. With both acceptors, the transfer of temoporfin stopped at a concentration much lower than the theoretical equilibrium values. The transfer of the less lipophilic drug Nile red was very rapid to both acceptors with equilibrium concentrations close to the expected values. The transfer results of temoporfin especially to the acceptor MLV obtained with the two detection techniques were comparable while the centrifugation technique indicated an apparently higher Nile red transfer rate than the flow cytometric technique. Both techniques are equally suitable to study the transfer of temoporfin, while the flow cytometric technique is advantageous to measure the very rapid transfer of Nile red.

Cryo‐electron microscopy and cryo‐electron tomography of nanoparticles

“…Many cryo‐TEM studies have been performed on lipid based nanoparticles, including liposome, lipopeptide, lipid liquid crystalline, and solid lipid nanoparticles . Lyotropic liquid crystalline nanoparticles represent a class of lipid‐based particles, which have highly ordered, internal water channels and which have strong potential for drug delivery applications .…”

“…Many cryo-TEM studies have been performed on lipid based nanoparticles, including liposome, lipopeptide, lipid liquid crystalline, and solid lipid nanoparticles. 43,[94][95][96][97][98][99][100][101][102][103][104] Lyotropic liquid crystalline nanoparticles represent a class of lipid-based particles, which have highly ordered, internal water channels and which have strong potential for drug delivery applications. 105 It was shown in the 1960s that lipids can self-assemble into non-lamellar phase structures, including a cubic phase and a hexagonal phase.…”

Comparison of drug release from liquid crystalline monoolein dispersions and solid lipid nanoparticles using a flow cytometric technique

“…Flow cytometry is mainly used for cell studies but it has also been used for the characterization and quantification of lipid particles like liposomes and emulsion droplets 30 , 31 , 32 , 33 , 34 . Recently, it has been used to investigate drug transfer between lipid particles 18 , 21 . Since it does not require a separation step between the donor and acceptor particles, the flow cytometric method is characterized by a very good time resolution and can detect large acceptor particles, which have a particle size of more than 1 µm 18 , 31 , 33 , 35 .…”

“…Recently, it has been used to investigate drug transfer between lipid particles 18 , 21 . Since it does not require a separation step between the donor and acceptor particles, the flow cytometric method is characterized by a very good time resolution and can detect large acceptor particles, which have a particle size of more than 1 µm 18 , 31 , 33 , 35 . Moreover, the high time-resolution of this technique allowed the study of the very rapid transfer and many data points in the rising part of the transfer curves were obtained.…”

“…To simulate the conditions encountered by the drug and drug carriers inside the body, the transfer from different colloidal carriers such as lipid nanoparticles into lipophilic acceptor compartments, which mimic the physiological environment, was studied. For example, release media was supplemented with albumin or unilamellar vesicles and oil/water (o/w) emulsion droplets 16 , 17 , 18 , 19 , 20 , 21 .…”