Gavini, Elisabetta and Rassu, Giovanna and Ferraro, Luca and Beggiato, Sarah and Alhalaweh, Amjad and Velaga, Sitaram and Marchetti, Nicola and Bandiera, Pasquale and Giunchedi, Paolo and Dalpiaz, Alessandro (2013) Influence of polymeric microcarriers on the in vivo intranasal uptake of an anti-migraine drug for brain targeting. European Journal of Pharmaceutics and Biopharmaceutics, Vol. 83 (2), p. 174-183. ISSN 0939-6411. eISSN 1873-3441. Article.
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The objective of this study was to investigate the effect of polymeric microcarriers on the in vivo intranasal uptake of an anti-migraine drug for brain targeting. Mucoadhesive powder formulations consisted of antimigraine drug, zolmitriptan, and chitosans (various molecular weights and types) or hydroxypropyl methylcellulose (HPMC). Their suitability for nasal administration was evaluated by in vitro and ex vivo mucoadhesion and permeation tests. The formulations based on chitosan glutamate (CG) or HPMC were tested in vivo because they showed good mucoadhesive properties and altered the permeation rate of the drug. The in vivo results from intravenous infusion and nasal aqueous suspension of the drug or nasal particulate powders were compared. The plasmatic AUC values obtained within 8 h following intravenous administration appeared about three times higher than those obtained by nasal administration, independent of the formulations. Zolmitriptan concentrations in the cerebrospinal fluid obtained from nasal and intravenous administrations were, respectively, 30 and 90 times lower than the concentrations of the drug in the blood. Thus, nasal administration potentiated the central zolmitriptan activity, allowing a reduction in the drug peripheral levels, with respect to the intravenous administration. Among nasally administered formulations, CG microparticles showed the highest efficacy in promoting the central uptake of zolmitriptan within 1 h.
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