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Open AccessArticle

Factorial Design as a Tool for the Optimization of PLGA Nanoparticles for the Co-Delivery of Temozolomide and O6-Benzylguanine

LEPABE—Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal
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Pharmaceutics 2019, 11(8), 401; https://doi.org/10.3390/pharmaceutics11080401
Received: 22 June 2019 / Revised: 23 July 2019 / Accepted: 8 August 2019 / Published: 10 August 2019
(This article belongs to the Special Issue PLGA Based Drug Carrier and Pharmaceutical Applications)
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Abstract

Poly(d,l-lactic-co-glycolic) (PLGA) nanoparticles (NPs) have been widely studied for several applications due to their advantageous properties, such as biocompatibility and biodegradability. Therefore, these nanocarriers could be a suitable approach for glioblastoma multiforme (GBM) therapy. The treatment of this type of tumours remains a challenge due to intrinsic resistance mechanisms. Thus, new approaches must be envisaged to target GBM tumour cells potentially providing an efficient treatment. Co-delivery of temozolomide (TMZ) and O6-benzylguanine (O6BG), an inhibitor of DNA repair, could provide good therapeutic outcomes. In this work, a fractional factorial design (FFD) was employed to produce an optimal PLGA-based nanoformulation for the co-loading of both molecules, using a reduced number of observations. The developed NPs exhibited optimal physicochemical properties for brain delivery (dimensions below 200 nm and negative zeta potential), high encapsulation efficiencies (EE) for both drugs, and showed a sustained drug release for several days. Therefore, the use of an FFD allowed for the development of a nanoformulation with optimal properties for the co-delivery of TMZ and O6BG to the brain. View Full-Text
Keywords: drug delivery; experimental design; fractional factorial design; O6-methylguanine DNA methyltransferase (MGMT) protein; glioblastoma multiforme drug delivery; experimental design; fractional factorial design; O6-methylguanine DNA methyltransferase (MGMT) protein; glioblastoma multiforme
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Ramalho, M.J.; Loureiro, J.A.; Coelho, M.A.N.; Pereira, M.C. Factorial Design as a Tool for the Optimization of PLGA Nanoparticles for the Co-Delivery of Temozolomide and O6-Benzylguanine. Pharmaceutics 2019, 11, 401.

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