期刊
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
卷 110, 期 -, 页码 31-38出版社
ELSEVIER
DOI: 10.1016/j.ejpb.2016.10.020
关键词
Lipid nanoparticles; Nanostructured lipid carriers; Single particle tracking; TIRE microscopy; Fluorescence superresolution microscopy; Drug delivery systems; Drug loading
资金
- German Research Foundation [1112]
- Freie Universitat Berlin
Drug loading capacity in nanostructured lipid carriers (NLC) depends on the formation of nanostructures within the lipid matrix. However, investigation of these nanostructures with sizes below the diffraction limit of visible light is quite challenging. Thus, until now the determination of structures and drug distribution within NLCs was not possible. Therefore, we aimed at developing a method to visualize the nanostructures within the lipid carriers. Model NLCs loaded with a lipophilic fluorescent drug mimetic, ATTO-Oxa12, were produced and investigated by single-molecule tracking and localization based superresolution microscopy. Results revealed spherical ATTO-Oxa12-filled nanostructures with diameters of similar to 70 nm and 120-130 nm, both smaller than the NLC size (similar to 160 nm). The ATTO-Oxa12 diffusion constant was calculated from the single-molecule traces (D >= 1 mu m(2)/s) and indicated the distribution of the model drug in the oily component. Together these data suggest the existence of drug-loaded oily nanocompartments, which could fill up to similar to 50% of the model NLCs' volume. In conclusion, a novel tool based on single-molecule microscopy is now available that allows for the precise determination of drug distribution and the characterization of lipid nanostructures, information that is paramount for optimizing lipid nanoparticle formulations. (C) 2016 Elsevier B.V. All rights reserved.
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