Modeling of ultra-small lipid nanoparticle surface charge for targeting glioblastoma
| Autor: | Tânia F.G.G. Cova, João Sousa, Carla Vitorino, Marı́a Luisa C. Vale, Lídia Gonçalves, Ana Miranda, Alberto A. C. C. Pais, António J. Almeida, Eduardo F. Marques, Maria Mendes |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Surface Properties
Drug Compounding Pharmaceutical Science Nanoparticle Antineoplastic Agents 02 engineering and technology Molecular Dynamics Simulation 010402 general chemistry 01 natural sciences Surface-Active Agents Cell Line Tumor Zeta potential Humans Nanotechnology Technology Pharmaceutical Surface charge Particle Size Cytotoxicity Lipid bilayer Drug Carriers Brain Neoplasms Chemistry 021001 nanoscience & nanotechnology Lipids 0104 chemical sciences Drug delivery Biophysics Nanoparticles Surface modification Glioblastoma 0210 nano-technology Drug carrier |
| Zdroj: | European Journal of Pharmaceutical Sciences. 117:255-269 |
| ISSN: | 0928-0987 |
| DOI: | 10.1016/j.ejps.2018.02.024 |
| Popis: | Surface modification of ultra-small nanostructured lipid carriers (usNLC) via introduction of a positive charge is hypothesized to prompt site-specific drug delivery for glioblastoma multiforme (GBM) treatment. A more effective interaction with negatively charged lipid bilayers, including the blood-brain barrier (BBB), will facilitate the nanoparticle access to the brain. For this purpose, usNLC with a particle size of 43.82 ± 0.03 nm and a polydispersity index of 0.224 were developed following a Quality by Design approach. Monomeric and gemini surfactants, either with conventional headgroups or serine-based ones, were tested for the surface modification, and the respective safety and efficacy to target GBM evaluated. A comprehensive in silico-in vitro approach is also provided based on molecular dynamics simulations and cytotoxicity studies. Overall, monomeric serine-derived surfactants displayed the best performance, considering altogether particle size, zeta potential, cytotoxic profile and cell uptake. Although conventional surfactants were able to produce usNLC with suitable physicochemical properties and cell uptake, their use is discouraged due to their high cytotoxicity. This study suggests that monomeric serine-derived surfactants are promising agents for developing nanosystems aiming at brain drug delivery. |
| Databáze: | OpenAIRE |
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