PMID- 31846696
OWN - NLM
STAT- MEDLINE
DCOM- 20201117
LR  - 20201117
IS  - 1879-0720 (Electronic)
IS  - 0928-0987 (Linking)
VI  - 143
DP  - 2020 Feb 15
TI  - Electrospun PVA-Dacarbazine nanofibers as a novel nano brain-implant for 
      treatment of glioblastoma: in silico and in vitro characterization.
PG  - 105183
LID - S0928-0987(19)30456-7 [pii]
LID - 10.1016/j.ejps.2019.105183 [doi]
AB  - Malignant glioblastoma (GB) treatment consists of resection surgery followed by 
      radiotherapy and chemotherapy (CT). Despite several implications, such as 
      systemic toxicity and low efficacy, CT continues to be used for GB therapy. 
      Aiming to overcome the blood-brain barrier (BBB) limitations, one of the most 
      promising approaches is the use of drug delivery systems (DDS) to treat the 
      cancer cells in situ. Dacarbazine (DTIC) is an antitumor agent that has limited 
      application given its high toxicity to healthy cells. However, it is effective 
      against GB recurrent cells. In this study, DTIC polymeric nanofibers (NF) were 
      successfully prepared, characterized and its in vitro anticancer efficacy was 
      determined. This system demonstrated high drug loading of 83.9 +/- 6.5%, good 
      stability and mechanical properties and sustained drug release, improved in tumor 
      pH (6.8). This controlled release prolonged the uptake of GB improving DTIC 
      antitumor effects such as DNA damage and cell death by apoptosis. Molecular 
      dynamics simulations revealed that DTIC interacts with PVA, possibly explaining 
      the controlled release of the drug. Therefore, DTIC NF brain-implants show great 
      potential as a promising drug delivery system for GB therapy.
CI  - Copyright (c) 2019 Elsevier B.V. All rights reserved.
FAU - Steffens, Luiza
AU  - Steffens L
AD  - Materials Research Institute, Athlone Institute of Technology, Athlone, Co. 
      Westmeath, Ireland; Laboratory of Genetic Toxicology, Federal University of 
      Health Sciences of Porto Alegre - UFCSPA, Sarmento Leite, 245, Lab.714, Porto 
      Alegre, Rio Grande do Sul, Brazil. Electronic address: luizasteffens@live.com.
FAU - Moras, Ana Moira
AU  - Moras AM
AD  - Laboratory of Genetic Toxicology, Federal University of Health Sciences of Porto 
      Alegre - UFCSPA, Sarmento Leite, 245, Lab.714, Porto Alegre, Rio Grande do Sul, 
      Brazil.
FAU - Arantes, Pablo Ricardo
AU  - Arantes PR
AD  - Laboratory of Genetic Toxicology, Federal University of Health Sciences of Porto 
      Alegre - UFCSPA, Sarmento Leite, 245, Lab.714, Porto Alegre, Rio Grande do Sul, 
      Brazil.
FAU - Masterson, Kevin
AU  - Masterson K
AD  - Materials Research Institute, Athlone Institute of Technology, Athlone, Co. 
      Westmeath, Ireland.
FAU - Cao, Zhi
AU  - Cao Z
AD  - Materials Research Institute, Athlone Institute of Technology, Athlone, Co. 
      Westmeath, Ireland.
FAU - Nugent, Michael
AU  - Nugent M
AD  - Materials Research Institute, Athlone Institute of Technology, Athlone, Co. 
      Westmeath, Ireland.
FAU - Moura, Dinara Jaqueline
AU  - Moura DJ
AD  - Laboratory of Genetic Toxicology, Federal University of Health Sciences of Porto 
      Alegre - UFCSPA, Sarmento Leite, 245, Lab.714, Porto Alegre, Rio Grande do Sul, 
      Brazil.
LA  - eng
PT  - Journal Article
DEP - 20191214
PL  - Netherlands
TA  - Eur J Pharm Sci
JT  - European journal of pharmaceutical sciences : official journal of the European 
      Federation for Pharmaceutical Sciences
JID - 9317982
RN  - 0 (Antineoplastic Agents, Alkylating)
RN  - 0 (Delayed-Action Preparations)
RN  - 0 (Drug Implants)
RN  - 7GR28W0FJI (Dacarbazine)
RN  - 9002-89-5 (Polyvinyl Alcohol)
SB  - IM
MH  - Antineoplastic Agents, Alkylating/*administration & dosage/chemistry
MH  - Brain/metabolism
MH  - Cell Line, Tumor
MH  - Cell Survival/drug effects
MH  - Dacarbazine/*administration & dosage/chemistry
MH  - Delayed-Action Preparations/administration & dosage/chemistry
MH  - *Drug Implants
MH  - Drug Liberation
MH  - Glioblastoma/*drug therapy
MH  - Humans
MH  - Molecular Dynamics Simulation
MH  - Nanofibers/*administration & dosage/chemistry
MH  - Polyvinyl Alcohol/*administration & dosage/chemistry
MH  - Technology, Pharmaceutical
OTO - NOTNLM
OT  - Dacarbazine
OT  - Electrospinning
OT  - Glioblastoma
OT  - Nanofibers
OT  - Polyvinyl alcohol
EDAT- 2019/12/18 06:00
MHDA- 2020/11/18 06:00
CRDT- 2019/12/18 06:00
PHST- 2019/10/10 00:00 [received]
PHST- 2019/12/07 00:00 [revised]
PHST- 2019/12/13 00:00 [accepted]
PHST- 2019/12/18 06:00 [pubmed]
PHST- 2020/11/18 06:00 [medline]
PHST- 2019/12/18 06:00 [entrez]
AID - S0928-0987(19)30456-7 [pii]
AID - 10.1016/j.ejps.2019.105183 [doi]
PST - ppublish
SO  - Eur J Pharm Sci. 2020 Feb 15;143:105183. doi: 10.1016/j.ejps.2019.105183. Epub 
      2019 Dec 14.