Factorial design as a tool for the optimization of plga nanoparticles for the co-delivery of temozolomide and o6-benzylguanine

• Type: Article in International Scientific Journal
• Date: 2019

Authors

Maria João Ramalho (Author) FEUP; Joana A. Loureiro (Author) FEUP; Manuel A. N. Coelho (Author) FEUP; Maria do Carmo Pereira (Author) FEUP

Journal

Title: Pharmaceutics

Vol. 11 No. 8

Pages: 1-18

ISSN: 1999-4923

Publisher: MDPI

Indexing

ISI Web of Knowledge - 0 Citations

Scopus - 8 Citations

Associated Projects

LEPABE-2-ECO-INNOVATION - LEPABE-2-ECO-INNOVATION

LEPABE - Laboratório de Engenharia de Processos, Ambiente, Biotecnologia e Energia

LEPABE - Projeto Estratégico do LEPABE - Laboratório de Engenharia de Processos, Ambiente, Biotecnologia e Energia

Other information

Authenticus ID: P-00R-1CV

DOI: 10.3390/pharmaceutics11080401

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 18