title: Solid lipid nanoparticles as intracellular drug transporters: an investigation of the uptake mechanism and pathway.
abstract: The aim of this work was to develop a systematic analysis of the cellular internalisation mechanism and pathway of solid lipid nanoparticles (SLN) internalisation. To evaluate if SLN show cell uptake and to understand the mechanism of internalisation, four human glioma cell lines (A172, U251, U373 and U87) and a human macrophage cell line (THP1) were used. For this purpose rhodamine 123 (R123) was loaded into SLN coated with polysorbate 60 and 80. Fluorescence microscopy and flow cell cytometry techniques were assessed to study internalisation of these systems within the cells. MTT studies were performed to evaluate the cytotoxicity of the R123-loaded SLN. To assess the SLN internalisation mechanism and intracellular pathway, excluding endocytosis mechanisms were applied. Our results revealed that R123-loaded SLN with mean size below 200 nm and slight negative surface charge (around -20 mV) have the ability to be internalised by gliomas in a higher amount than by macrophages. The mechanism of internalisation was found to be mainly through a clathrin-dependent endocytic pathway. In addition, the cytotoxicity of SLN was higher for gliomas than for macrophages. These results suggest that SLN can be a promising alternative in brain tumours treatment.
authors.affiliation: Laboratory of Pharmaceutical Technology/Centre of Research in Pharmaceutical Sciences (LTF/CICF), Faculty of Pharmacy, University of Porto, Rua Aníbal Cunha n°164, 4050-047 Porto, Portugal. susana.martins@ff.up.pt
authors.forename: S
authors.initials: S
authors.lastname: Martins
authors.forename: S
authors.initials: S
authors.lastname: Costa-Lima
authors.forename: T
authors.initials: T
authors.lastname: Carneiro
authors.forename: A
authors.initials: A
authors.lastname: Cordeiro-da-Silva
authors.forename: E B
authors.initials: EB
authors.lastname: Souto
authors.forename: D C
authors.initials: DC
authors.lastname: Ferreira
mesh_terms: D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D002966:Clathrin / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004705:Endocytosis / Q000187:drug effects; D005434:Flow Cytometry; D005456:Fluorescent Dyes / Q000737:chemistry / Q000378:metabolism; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008856:Microscopy, Fluorescence; D053758:Nanoparticles; D036103:Nanotechnology; D010168:Palmitates / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D010316:Particle Size; D011136:Polysorbates / Q000737:chemistry; D020112:Rhodamine 123 / Q000737:chemistry / Q000378:metabolism; D013499:Surface Properties; D013501:Surface-Active Agents / Q000737:chemistry; D013678:Technology, Pharmaceutical; D013997:Time Factors; D014885:Waxes
chemical_list: D002966:Clathrin; D004337:Drug Carriers; D005456:Fluorescent Dyes; D010168:Palmitates; D011136:Polysorbates; D013501:Surface-Active Agents; D014885:Waxes; D020112:Rhodamine 123; C006957:cetyl palmitate