In vitro evaluation of two different types of obidoxime-loaded nanoparticles for cytotoxicity and blood-brain barrier transport
Toxicology Letters, cilt.330, ss.53-58, 2020 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 330
- Basım Tarihi: 2020
- Doi Numarası: 10.1016/j.toxlet.2020.03.018
- Dergi Adı: Toxicology Letters
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aerospace Database, BIOSIS, CAB Abstracts, Chimica, Communication Abstracts, EMBASE, Environment Index, Food Science & Technology Abstracts, MEDLINE, Metadex, Veterinary Science Database, Civil Engineering Abstracts
- Sayfa Sayıları: ss.53-58
- Anahtar Kelimeler: Nanoparticles, Cytotoxicity, Nerve agents, Obidoxime, Blood -brain barrier
- Sağlık Bilimleri Üniversitesi Adresli: Evet
Özet
Nerve agents (NA) are chemical warfare munitions and their exposure causes a progressive inhibition of acetylcholinesterase (AChE). This inhibition causes NA-induced brain damage in central nervous system (CNS). Oximes reactivate AChE in both the peripheral nervous system and the CNS. Transport of the oxime across the blood–brain barrier (BBB) in the existed therapeutic concentrations at the brain parenchyma determines the effectiveness of antidote therapy on respiratory depression and NA-induced brain damage. However, oximes could not cross the BBB in therapeutic concentrations. The aim of this study was to load AChE reactivator obidoxime chloride to PLGA and PEG-b-PLGA nanoparticles and to improve the BBB transport of the molecule. Brain microvascular endothelial cells were used as the BBB model. 79.3 ± 4.2% of obidoxime was released from PLGA nanoparticles and 88.2 ± 4.4% of obidoxime was released from PEG-b-PLGA nanoparticles within 24 h. It was found that PEG-b-PLGA nanoparticles were ideal drug carrier because of its low tissue toxicity, few side effects, and controllable drug release profile. Transport efficiency of obidoxime across the BBB is a major challenge in the prevention of the CNS, the effectiveness of NA poisoning and new strategies like using obidoxime-loaded PEG-b-PLGA nanoparticles could overcome this challenge for the management of NA-induced brain damage.