Nose to brain delivery of eletriptan hydrobromide nanoparticles: Preparation, in vitro/in vivo evaluation and effect on trigeminal activation

被引:30
作者
Esim, Ozgur [1 ]
Savaser, Ayhan [1 ]
Ozkan, Cansel K. [1 ]
Oztuna, Ali [2 ]
Goksel, Berk Alp [3 ,4 ]
Ozler, Mehmet [5 ]
Tas, Cetin [6 ]
Ozkan, Yalcin [1 ]
机构
[1] Univ Hlth Sci, Gulhane Fac Pharm, Dept Pharmaceut Technol, TR-06018 Ankara, Turkey
[2] Gulhane Training & Res Hosp, Dept Med Genet, TR-06018 Ankara, Turkey
[3] Univ Hlth Sci, Dept Anim Expt, Gulhane Inst Hlth Sci, TR-06018 Ankara, Turkey
[4] Univ Hlth Sci, Res Ctr, TR-06018 Ankara, Turkey
[5] Univ Hlth Sci, Gulhane Fac Med, Dept Physiol, TR-06018 Ankara, Turkey
[6] Yeditepe Univ, Fac Pharm, Dept Pharmaceut Technol, TR-34755 Istanbul, Turkey
关键词
Migraine; Nose to brain delivery; Eletriptan hydrobromide; P-glycoprotein; Nanoparticle; CHITOSAN NANOPARTICLES; NUCLEUS CAUDALIS; FOS; TRANSPORT; RELEASE; DRUG; MODEL; DICLOFENAC; EXPRESSION; PACLITAXEL;
D O I
10.1016/j.jddst.2020.101919
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Migraine is a chronic disorder of the brain and acts through peripheral trigeminal activation. Thus, both central and peripheral stimulations can play a part in sensitization and activation of trigeminal neurons. Intranasal drug delivery offers a possible solution due to direct link to trigeminal nerves. A wide variety of therapeutic compounds can be administered intranasally for their topical, systemic and central nervous system (CNS) action. In this study, eletriptan hydrobmmide (EH) loaded PLGA nanoparticles were prepared and their antimigraine activity was evaluated after intranasal administration. It was shown that PLGA nanoparticles had an average particle size of 201.5 +/- 13.6 nm and zeta potential value of - 17.3 +/- 2.11 mV. After cellular uptake and P-glycoprotein efflux studies, EH nanoparticles were shown to overcome P-glycoprotein mediated drug efflux. The pharmacokinetic parameters revealed a marked improvement in the CNS permeation behavior of intranasal EH loaded nanoparticle administration as compared to intravenous administration of drug (p < 0.05). There was two times higher AUC(b)(ra)(in) representing a higher total amount of drug reaching to the brain (AUC(0-infinity) = 100.34 +/- 29.13 ng/ml.h for intranasal nanoparticle administration and AUC(0-infinity) = 60.01 +/- 11.30 ng/ml.h for intravenous solution). We showed that expressions of c-fos and substance P are dependent on the drug that reached to the brain and intranasal drug administration prolonged the expression of substance P and c-fos mRNA levels. Based on the results, intranasal PLGA nanoparticle administration of EH may be evaluated as a better treatment option for migraine therapy.
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页数:10
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