Modeling of ultra-small lipid nanoparticle surface charge for targeting glioblastoma

European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences
Maria MendesCarla Vitorino

Abstract

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...Continue Reading

Citations

May 20, 2020·Frontiers in Pharmacology·Shuwen CaoPhei Er Saw
Mar 28, 2021·Archivum Immunologiae Et Therapiae Experimentalis·Benita Ortega-BerlangaGabriela Navarro-Tovar
Nov 22, 2020·International Journal of Pharmaceutics·João BassoCarla Vitorino

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