Micellar Nanocarriers: Potential Nose-to-Brain Delivery of Zolmitriptan as Novel Migraine Therapy

Jain, Ratnesh; Nabar, Swapna; Dandekar, Prajakta; Patravale, Vandana

doi:10.1007/s11095-009-0041-x

Cited by 79 publications

(24 citation statements)

References 34 publications

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“…39%, 5.78%, 144.25, 3.46, and 99.3, 70.07 for intranasal 99m Tc-PM7 and intranasal 99m Tc-CZ solution, respectively. These results are in accordance with Jain et al (2010) and Kanazawa et al (2011) who found that intranasal PM have a very high potential for brain targeting of zolmitriptan and coumarin, respectively.…”

Section: Biodistribution Studysupporting

confidence: 92%

Intranasal brain-targeted clonazepam polymeric micelles for immediate control of status epilepticus: in vitro optimization, ex vivo determination of cytotoxicity, in vivo biodistribution and pharmacodynamics studies

et al. 2016

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Clonazepam (CZ) is an anti-epileptic drug used mainly in status epilepticus (SE). The drug belongs to Class II according to BCS classification with very limited solubility and high permeability and it suffers from extensive first-pass metabolism. The aim of the present study was to develop CZ-loaded polymeric micelles (PM) for direct brain delivery allowing immediate control of SE. PM were prepared via thin film hydration (TFH) technique adopting a central composite face-centered design (CCFD). The seventeen developed formulae were evaluated in terms of entrapment efficiency (EE), particle size (PS), polydispersity index (PDI), zeta potential (ZP), and in vitro release. For evaluating the in vivo behavior of the optimized formula, both biodistrbution using 99m Tc-radiolabeled CZ and pharmacodynamics studies were done in addition to ex vivo cytotoxicty. At a drug:Pluronic Õ P123:Pluronic Õ L121 ratio of 1:20:20 (PM7), a high EE, ZP, Q8h, and a low PDI was achieved. The biodistribution studies revealed that the optimized formula had significantly higher drug targeting efficiency (DTE ¼ 242.3%), drug targeting index (DTI ¼ 144.25), and nose-to-brain direct transport percentage (DTP ¼ 99.30%) and a significant prolongation of protection from seizures in comparison to the intranasally administered solution with minor histopathological changes. The declared results reveal the ability of the developed PM to be a strong potential candidate for the emergency treatment of SE.

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Section: Biodistribution Studysupporting

confidence: 92%

Intranasal brain-targeted clonazepam polymeric micelles for immediate control of status epilepticus: in vitro optimization, ex vivo determination of cytotoxicity, in vivo biodistribution and pharmacodynamics studies

et al. 2016

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“…The DTI values >1 could confirm the direct pathway from nose to brain (Wang, Jiang, Lu, 2003). These findings are in line with Jain et al (2010), Kanazawa et al (2011) who found that micellar nanocarriers of zolmitriptan and coumarin increase the nose-to-brain uptake, via the olfactory region of the nasal cavity. Finally, the higher value of DTI, DTE (%) and DTP (%) suggested that HP-SLNs have better brain targeting potential as compared to HP-Sol administered intranasally.…”

Section: In Vivo Studies For the Determination Of Pharmacokinetic And Bsupporting

confidence: 85%

Development of a new HPLC method for in vitro and in vivo studies of haloperidol in solid lipid nanoparticles

Yasir

Sara²,

Som³

2017

Braz. J. Pharm. Sci.

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A simple and sensitive HPLC method was developed and validated for the quantification of haloperidol in solid lipid nanoparticles (SLNs). The developed method was used for detection of shelf life of haloperidol in SLNs. Calibration curve of haloperidol was also constructed in rat plasma using loratidine as internal standard. In vivo studies were performed on rats and concentration of haloperidol in brain and blood was measured for the determination of various pharmacokinetic and hence brain targeting parameters. Chromatogram separation was achieved using C18 column as stationary phase. The mobile phase consisted of 100 mM/L potassium dihydrogen phosphate-acetonitrile-TEA (10:90:0.1, v/v/v) and the pH was adjusted with o-phosphoric acid to 3.5. Flow rate of mobile phase was 2 mL/minute and eluents were monitored at 230 nm using UV/VIS detector. The method was validated for linearity, precision, accuracy, reproducibility, limit of detection (LOD) and limit of quantification (LOQ). Linearity for haloperidol was in the range of 1-16 µg/mL. The value of LOD and LOQ was found to be 0.045 and 0.135 μg/mL respectively. The shelf life of SLNs formulation was found to be 2.31 years at 4 o C. Various parameters like drug targeting index (DTI), drug targeting efficiency (DTE) and nose-to-brain direct transport (DTP) were determined for HP-SLNs & HP-Sol administered intranasally to evaluate the extent of nose-to-brain delivery. The value of DTI, DTE and DTP for HP-SLNs was found to be 23.62, 2362.43 % and 95.77% while for HP-Sol, values were 11.28, 1128.61 % and 91.14 % respectively.Uniterms: Haloperidol/quantification. Haloperidol/pharmacokinetic. Haloperidol/in vitro study. Haloperidol/in vivo study. High performance liquid chromatography/solid lipid nanoparticles. Plasma. Validation. Brain targeting.

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“…Direct transport of drugs to the brain circumventing the brain-barriers following intranasal administration provides a unique feature and better option to target drugs to the brain. Intranasal administration of ZT for direct transport to the brain via microemulsion (Vyas et al, 2005), polymeric microparticles (Gavini et al, 2013), nanoparticles (Girotra et al, 2016), and micellar nanocarriers (Jain et al, 2010) have been developed. ZT nasal spray was approved by the FDA in 2003.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2016

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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.

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Micellar Nanocarriers: Potential Nose-to-Brain Delivery of Zolmitriptan as Novel Migraine Therapy

Abstract: The investigation indicated the potential of the developed nanocarrier as an effective new-generation vehicle for brain targeting of zolmitriptan.

Cited by 79 publications

References 34 publications

Intranasal brain-targeted clonazepam polymeric micelles for immediate control of status epilepticus: in vitro optimization, ex vivo determination of cytotoxicity, in vivo biodistribution and pharmacodynamics studies

Intranasal brain-targeted clonazepam polymeric micelles for immediate control of status epilepticus: in vitro optimization, ex vivo determination of cytotoxicity, in vivo biodistribution and pharmacodynamics studies

Development of a new HPLC method for in vitro and in vivo studies of haloperidol in solid lipid nanoparticles

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

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