Abstract
Background: Status epilepticus is associated with substantial morbidity and neuronal necrosis, and the duration of the seizure would affect its following complications. Eliminating the duration would have valuable outcomes; however, the presence of BBB is an obstacle. The purpose of the current study was to achieve a nose-to-brain magnetic drug delivery system to accelerate the onset of action, and to reduce the mucociliary clearance via implementing the magnetic field.
Materials and Methods: The drug-entrapped magnetic nanoaggregates were prepared via a 2-step method, synthesis of the magnetic nanoparticles and drug loading. Optimization of the variables, including ammonium hydroxide:water ratio, beta-cyclodextrin%, duration of the mixing time, amount of Pluronic, and drug:magnetic nanoaggregates mass ratio was performed according to particle size, PDI, zeta potential, release profile and entrapment efficiency. The efficacy of optimized formulation was assessed in the animal model.
Results: According to the analysis performed by the software, drug-to-nanoparticle ratio and the duration of mixing time were found to be significantly effective (p < 0.05) for entrapment efficiency and particle size distribution, respectively. The optimum formulation with an approximate average size of 581 nm and 61% entrapment efficiency was obtained, which released about 80% of its drug content within the first 20 minutes. The in vivo efficacy was significantly improved (p < 0.05) by administration of magnetic nanoaggregates in the presence of a simple external magnet placed on the glabellar region of the animals, compared to the control groups.
Conclusion: This drug delivery system could be suggested as a fast-acting alternative for seizure cessation in status epilepticus emergencies.
Graphical Abstract
[http://dx.doi.org/10.1016/S0140-6736(12)61381-6] [PMID: 23021288]
[http://dx.doi.org/10.1080/21646821.2018.1428455] [PMID: 29562876]
[http://dx.doi.org/10.1007/s11910-017-0758-6] [PMID: 28425015]
[http://dx.doi.org/10.1016/S0140-6736(18)32596-0] [PMID: 30686584]
[http://dx.doi.org/10.4103/0972-2327.56312] [PMID: 20174493]
[http://dx.doi.org/10.1016/j.seizure.2016.11.001] [PMID: 27890484]
[http://dx.doi.org/10.1016/B978-0-12-814001-7.00010-X]
[http://dx.doi.org/10.1063/1.5035388] [PMID: 29983837]
[http://dx.doi.org/10.1111/epi.12027] [PMID: 23205961]
[http://dx.doi.org/10.1111/j.1528-1157.1992.tb02341.x] [PMID: 1628578]
[http://dx.doi.org/10.1016/j.seizure.2019.06.012] [PMID: 31394367]
[http://dx.doi.org/10.1016/S0140-6736(00)04516-5] [PMID: 11343735]
[PMID: 12163916]
[http://dx.doi.org/10.1179/027249302125001598] [PMID: 12369496]
[PMID: 22802683]
[http://dx.doi.org/10.1021/cm900268z]
[http://dx.doi.org/10.1111/j.1528-1157.1993.tb05905.x] [PMID: 8385002]
[http://dx.doi.org/10.1136/bmj.321.7253.83] [PMID: 10884257]
[http://dx.doi.org/10.3390/pharmaceutics13101640] [PMID: 34683933]
[http://dx.doi.org/10.1039/D1BM01251G] [PMID: 34652351]
[http://dx.doi.org/10.1166/jnn.2014.8537] [PMID: 24745232]
[http://dx.doi.org/10.1016/S0169-409X(98)00054-4] [PMID: 10837708]
[http://dx.doi.org/10.1208/s12249-015-0294-0] [PMID: 25698083]
[http://dx.doi.org/10.1039/b9nr00253g] [PMID: 20644760]
[http://dx.doi.org/10.1039/C7RA02398G]
[http://dx.doi.org/10.1007/s10847-013-0378-y]
[http://dx.doi.org/10.1080/21691401.2018.1468340]
[http://dx.doi.org/10.3390/ijms21114079] [PMID: 32517363]
[http://dx.doi.org/10.1016/S0304-3940(02)00423-8] [PMID: 12113905]
[http://dx.doi.org/10.1111/j.1528-1167.2008.01582.x] [PMID: 18363707]