Combination delivery of two oxime-loaded lipid nanoparticles: Time-dependent additive action for prolonged rat brain protection - Normandie Université Access content directly
Journal Articles Journal of Controlled Release Year : 2018

Combination delivery of two oxime-loaded lipid nanoparticles: Time-dependent additive action for prolonged rat brain protection

T.N. Pashirova
  • Function : Author
I.V. Zueva
  • Function : Author
K.A. Petrov
  • Function : Author
V.M. Babaev
  • Function : Author
E.A. Burilova
  • Function : Author
D.A. Samarkina
  • Function : Author
I.K. Rizvanov
  • Function : Author
E.B. Souto
  • Function : Author
L.Y. Zakharova
  • Function : Author
O.G. Sinyashin
  • Function : Author

Abstract

A novel approach for brain protection against poisoning by organophosphorus agents is developed based on the combination treatment of dual delivery of two oximes. Pralidoxime chloride (2-PAM) and a novel reactivator, 6-(5-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)pentyl)-3-hydroxy picolinaldehyde oxime (3-HPA), have been loaded in solid-lipid nanoparticles (SLNs) to offer distinct release profile and systemic half-life for both oximes. To increase the therapeutic time window of both oximes, SLNs with two different compartments were designed to load each respective drug. Oxime-loaded SLNs of hydrodynamic diameter between 100 and 160 nm and negative zeta potential (−30 to −25 mV) were stable for a period of 10 months at 4 °C. SLNs displayed longer circulation time in the bloodstream compared to free 3-HPA and free 2-PAM. Oxime-loaded SLNs were suitable for intravenous (iv) administration. Paraoxon-poisoned rats (0.8 × LD50) were treated with 3-HPA-loaded SLNs and 2-PAM+3-HPA-loaded SLNs at the dose of 3-HPA and 2-PAM of 5 mg/kg. Brain AChE reactivation up to 30% was slowly achieved in 5 h after administration of 3-HPA-SLNs. For combination therapy with two oximes, a time-dependent additivity and increased reactivation up to 35% were observed.
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Dates and versions

hal-02024524 , version 1 (19-02-2019)

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T.N. Pashirova, Anissa Braïki, I.V. Zueva, K.A. Petrov, V.M. Babaev, et al.. Combination delivery of two oxime-loaded lipid nanoparticles: Time-dependent additive action for prolonged rat brain protection. Journal of Controlled Release, 2018, 290, pp.102-111. ⟨10.1016/j.jconrel.2018.10.010⟩. ⟨hal-02024524⟩
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