PMID- 31405159
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 1999-4923 (Print)
IS  - 1999-4923 (Electronic)
IS  - 1999-4923 (Linking)
VI  - 11
IP  - 8
DP  - 2019 Aug 10
TI  - Factorial Design as a Tool for the Optimization of PLGA Nanoparticles for the 
      Co-Delivery of Temozolomide and O6-Benzylguanine.
LID - 10.3390/pharmaceutics11080401 [doi]
LID - 401
AB  - 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.
FAU - Ramalho, Maria Joao
AU  - Ramalho MJ
AUID- ORCID: 0000-0003-2428-7520
AD  - LEPABE-Laboratory for Process Engineering, Environment, Biotechnology and Energy, 
      Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 
      Porto, Portugal.
FAU - Loureiro, Joana A
AU  - Loureiro JA
AD  - LEPABE-Laboratory for Process Engineering, Environment, Biotechnology and Energy, 
      Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 
      Porto, Portugal.
FAU - Coelho, Manuel A N
AU  - Coelho MAN
AD  - LEPABE-Laboratory for Process Engineering, Environment, Biotechnology and Energy, 
      Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 
      Porto, Portugal.
FAU - Pereira, Maria Carmo
AU  - Pereira MC
AD  - LEPABE-Laboratory for Process Engineering, Environment, Biotechnology and Energy, 
      Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 
      Porto, Portugal. mcsp@fe.up.pt.
LA  - eng
GR  - UID/EQU/00511/2019/Fundacao para a Ciencia e a Tecnologia/
GR  - POCI-01-0145-FEDER-006939/European Regional Development Fund/
GR  - LEPABE-2-ECO-INNOVATION" - NORTE-01-0145-FEDER-000005/European Regional 
      Development Fund/
GR  - PD/BD/105984/2014/Fundacao para a Ciencia e a Tecnologia/
PT  - Journal Article
DEP - 20190810
PL  - Switzerland
TA  - Pharmaceutics
JT  - Pharmaceutics
JID - 101534003
PMC - PMC6722980
OTO - NOTNLM
OT  - O6-methylguanine DNA methyltransferase (MGMT) protein
OT  - drug delivery
OT  - experimental design
OT  - fractional factorial design
OT  - glioblastoma multiforme
COIS- The authors declare no conflict of interest.
EDAT- 2019/08/14 06:00
MHDA- 2019/08/14 06:01
PMCR- 2019/08/01
CRDT- 2019/08/14 06:00
PHST- 2019/06/22 00:00 [received]
PHST- 2019/07/23 00:00 [revised]
PHST- 2019/08/08 00:00 [accepted]
PHST- 2019/08/14 06:00 [entrez]
PHST- 2019/08/14 06:00 [pubmed]
PHST- 2019/08/14 06:01 [medline]
PHST- 2019/08/01 00:00 [pmc-release]
AID - pharmaceutics11080401 [pii]
AID - pharmaceutics-11-00401 [pii]
AID - 10.3390/pharmaceutics11080401 [doi]
PST - epublish
SO  - Pharmaceutics. 2019 Aug 10;11(8):401. doi: 10.3390/pharmaceutics11080401.