Trans-nasal zolmitriptan novasomes: in-vitro preparation, optimization and in-vivo evaluation of brain targeting efficiency

Abstract

Migraine attack is a troublesome physiological condition associated with throbbing, intense headache, in one half of the head. Zolmitriptan is a potent second-generation triptan, prescribed for patients with migraine attacks, with or without an aura, and cluster headaches. The absolute bioavailability of zolmitriptan is about 40% for oral administration; due to hepatic first metabolism. Nasal administration would circumvent the pre-systemic metabolism thus increasing the bioavailability of zolmitriptan. In addition, due to the presence of microvilli and high vasculature, the absorption is expected to be faster compared to oral route. However, the bioavailability of nasal administered drugs is particularly restricted by poor membrane penetration. Thus, the aim of this work is to explore the potential of novel nanovesicular fatty acid enriched structures (novasomes) for effective and enhanced nasal delivery of zolmitriptan and investigate their nose to brain targeting potential. Novasomes were prepared using nonionic surfactant, cholesterol in addition to a free fatty acid. A 2 3 full factorial design was adopted to study the influence of the type of surfactant, type of free fatty acid and ratio between the free fatty acid and the surfactant on novasomes properties. The particle size, entrapment efficiency, polydispersity index, zeta potential and % zolmitriptan released after 2 h were selected as dependent variables. Novasomes were further optimized using Design Expert Õ software (version 7; Stat-Ease Inc., Minneapolis, MN), and an optimized formulation composed of Span Õ 80:Cholesterol:stearic acid (in the ratio 1:1:1) was selected. This formulation showed zolmitriptan entrapment of 92.94%, particle size of 149.9 nm, zeta potential of À55.57 mV, and released 48.43% zolmitriptan after 2 h. The optimized formulation was further examined using transmission electron microscope, which revealed non-aggregating multi-lamellar nanovesicles with narrow size distribution. DSC, XRD examination of the optimized formulation confirmed that the drug have been homogeneously dispersed throughout the novasomes in an amorphous state. In-vivo bio-distribution studies of 99m Tc radio-labeled intranasal zolmitriptan loaded novasomes were done on mice, the pharmacokinetic parameters were compared with those following administration of intravenous 99m Tc-zolmitriptan solution. Results revealed the great enhancement in zolmitriptan targeting to the brain, with drug targeting potential of about 99% following intranasal administration of novasomes compared with the intravenous drug solution. Zolmitriptan loaded novasomes administered via the nasal route may therefore constitute an advance in the management of acute migraine attacks.

Contribution of both olfactory and systemic pathways for brain targeting of nimodipine-loaded lipo-pluronics micelles: in vitro characterization and in vivo biodistribution study after intranasal and intravenous delivery

“…This is because reduced 99m Tc will be slightly re-oxidized when a large excess of dithionite is added resulting in increased level of free 99m TcO 4 À (Mayhew, 1978). As noticed, there is no colloidal species other than 99m TcO 2 obtained in the reaction which is a major advantage of using Na 2 S 2 O 4 as a reducing agent in preparing technetium radiopharmaceuticals avoiding colloidal stannic oxide interference for stannous chloride prepared radiopharmaceuticals (Ferreira et al, 2015;Abd-Elal et al, 2016).…”

“…The formulations were administered at the openings of the nostrils. The procedure was performed gently, allowing the animals to inhale all the preparation (Abd-Elal et al, 2016). At different time intervals (0.25, 0.5, 1, 2, 4, 8, and 24 h), three mice were anesthetized by chloroform.…”

“…The evaluation of the NM brain targeting after IN application was estimated by using drug targeting efficiency percentage (DTE %) (Abd-Elal et al, 2016). DTE percentages (that represent the time average partitioning ratio) of NM formulations were calculated according to the following equation:…”

Mixed cationic liposomes for brain delivery of drugs by the intranasal route: The acetylcholinesterase reactivator 2-PAM as encapsulated drug model

“…Their surface can be easily modified to provide them with multiple functions [17]. This has already been demonstrated for improvement of intranasal delivery [18] of rivastigmine [19,20], donepezil [21], zolmitriptan [22].…”

Preparation, Characterization, Cytotoxicity and Biological Evaluation of ^99mTc-Doxorubicin-Epigallocatechingallate Functionalized Gold Nanoparticles as a New Generation of Theranostic Radiopharmaceutical

“…Reaction time effect on radiolabeling yield was also studied (5-60 min). Ascending paper chromatography was used for analysis of RCY using acetone as a mobile phase to determine free 99m TcO 4 -% and water:ethanol:ammonia mixture (5:2:1 v:v:v) to determine colloidal impurities percentage [54,55].…”