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Title: Biomimeting ultra-small lipid nanoconstructs for glioblastoma treatment: A computationally guided experimental approach
Authors: Mendes, Maria
Basso, João
Silva, Jessica
Cova, Tânia 
Sousa, João
Pais, Alberto 
Vitorino, Carla 
Keywords: Biomimeting; Design of experiments; Drug repurposing; Glioblastoma; Process parameters; Ultra-small nanostructured lipid carriers
Issue Date: 25-Sep-2020
Publisher: Elsevier
Project: POCI-01-0145-FEDER- 016648 
UID/NEU/04539/ 2013-2020 
Serial title, monograph or event: International Journal of Pharmaceutics
Volume: 587
Issue: 119661
Abstract: Ultra-small nanostructured lipid carriers (usNLCs) are stable, biocompatible and biodegradable colloidal systems, claiming a broad set of advanced features suitable for cancer drug delivery. To unleash their potential in glioblastoma research and therapy, we have developed an usNLC prototype able to co-encapsulate atorvastatin calcium and curcumin, as repurposed drugs previously screened from molecular dynamics simulations. The novelty not only relies on the drug repositioning approach, but also on a robust computational methodology utilized for formulation optimization, under the umbrella of multivariate analysis and full factorial designs. A coating procedure with red blood cell membranes is ultimately hypothesized, aiming at integrating the biomimetic concept into usNLCs for glioblastoma therapeutics. The formulation composition and process parameters, that demonstrated a high-risk level for the final quality and performance of the usNLCs, include the solid:liquid lipid ratio, type and concentration of liquid lipids and surfactants, along with the type of production method. Particles with an average diameter of ca. 50 nm, and a polydispersity index lower than 0.3 were produced, exhibiting high stability, up-scalability, drug protection and sustained co-release properties, meeting the suitable critical quality attributes for intravenous administration. Also, a Taguchi design was successfully applied to optimizing usNLCs as cell membrane-coating technology.
ISSN: 03785173
DOI: 10.1016/j.ijpharm.2020.119661
Rights: openAccess
Appears in Collections:I&D CQC - Artigos em Revistas Internacionais

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