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

• Type: Article in International Scientific Journal
• Date: 2018-02-24

Authors

Maria Mendes (Author) Other; Ana Miranda (Author) Other; Tânia Cova (Author) Other; Lídia Gonçalves (Author) Other; António J. Almeida (Author) Other; João J. Sousa (Author) Other; Maria L. C. do Vale (Author) FCUP; Eduardo F. Marques (Author) FCUP; Alberto Pais (Author) Other; Carla Vitorino (Author) Other

Journal

Title: European Journal of Pharmaceutical Sciences

Vol. 117

Pages: 255-269

ISSN: 0928-0987

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 36 Citations

Scopus - 38 Citations

Other information

Authenticus ID: P-00N-Q9V

DOI: 10.1016/j.ejps.2018.02.024

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 15