title: Transport of stearic acid-based solid lipid nanoparticles (SLNs) into human epithelial cells.
abstract: Development of drug delivery systems, as much as the drug molecule itself, is an important consideration for improving drug absorption and bioavailability. The mechanisms by which drug carriers enter target cells can differ depending on their size, surface properties and components. Solid lipid nanoparticles (SLNs) have gained an increased attention in recent years and are the drug carriers of interest in this paper. They are known to breach the cell-membrane barrier and have been actively sought to transport biomolecules. Previous studies by our group, and also other groups, provided an extensive characterization of SLNs. However, few studies have investigated the uptake of SLNs and these have had limited mechanistic focus. The aim of this work was to investigate the pathway of uptake of SLNs by human epithelial cells i.e., lung A549 and cervical HeLa cells. To the best of our knowledge, this is first study that investigates the cellular uptake of SLNs by human epithelial cells. The mechanism of cellular uptake was deciphered using pharmacologic inhibitors (sucrose, potassium-free buffer, filipin and cytochalasin B). Imaging techniques and flow assisted cell sorting (FACS) were used to assess the cellular uptake of SLNs loaded with rhodamine 123 as a fluorescent probe. This study provided evidence that the cellular uptake of SLNs was energy-dependent, and the endocytosis of SLNs was mainly dependent on clathrin-mediated mechanisms. The establishment of entry mechanism of SLNs is of fundamental importance for future facilitation of SLNs as biological or drug carriers.
authors.affiliation: Department of Chemistry and Biotechnology, Faculty of Science, Engineering and Technology, Swinburne University of Technology, Hawthorn, Melbourne, Australia.
authors.forename: Rohan M
authors.initials: RM
authors.lastname: Shah
authors.affiliation: Department of Chemistry and Biotechnology, Faculty of Science, Engineering and Technology, Swinburne University of Technology, Hawthorn, Melbourne, Australia.
authors.forename: Dhivya
authors.initials: D
authors.lastname: Rajasekaran
authors.affiliation: Immune Signalling Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Australia; Cell Biology Laboratory, Center for Micro-Photonics, Faculty of Science, Engineering and Technology, Swinburne University of Technology Melbourne, Australia.
authors.forename: Mandy
authors.initials: M
authors.lastname: Ludford-Menting
authors.affiliation: Department of Chemistry and Biotechnology, Faculty of Science, Engineering and Technology, Swinburne University of Technology, Hawthorn, Melbourne, Australia.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Eldridge
authors.affiliation: Department of Chemistry and Biotechnology, Faculty of Science, Engineering and Technology, Swinburne University of Technology, Hawthorn, Melbourne, Australia.
authors.forename: Enzo A
authors.initials: EA
authors.lastname: Palombo
authors.affiliation: Department of Chemistry and Biotechnology, Faculty of Science, Engineering and Technology, Swinburne University of Technology, Hawthorn, Melbourne, Australia. Electronic address: iharding@swin.edu.au.
authors.forename: Ian H
authors.initials: IH
authors.lastname: Harding
mesh_terms: D001692:Biological Transport; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003571:Cytochalasin B / Q000494:pharmacology; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods; D004705:Endocytosis; D004847:Epithelial Cells / Q000737:chemistry / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D018613:Microscopy, Confocal; D015394:Molecular Structure; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D020112:Rhodamine 123 / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D004337:Drug Carriers; D008055:Lipids; D020112:Rhodamine 123; D003571:Cytochalasin B
keywords: Cellular uptake; Clathrin-mediated endocytosis; Microwave-assisted Microemulsion technique; Pharmacologic inhibitors; Rhodamine 123; Solid lipid nanoparticles