Investigating the cubosomal ability for transnasal brain targeting: In vitro optimization, ex vivo permeation and in vivo biodistribution

Abdelrahman, Fatma Elzahraa; Elsayed, Ibrahim; Gad, Mary Kamal; Badr, Ahmed Noah; Mohamed, M. I.

doi:10.1016/j.ijpharm.2015.05.064

Cited by 75 publications

(52 citation statements)

References 51 publications

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“…Formula F3 contained glycerol with high concentration as the permeation enhancers leading to more permeation of drug into the skin. The same results were confirmed the penetration enhancer of glycerol were presented previously [20,34,35].…”

Section: Ex Vivo Skin Permeationsupporting

confidence: 91%

A Novel Topical Spray Formulation for Ginkgo Bioloba for Antifungal Activity

Aah¹

2016

J Nanomed Nanotechnol

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The aim of this study is to prove the antifungal and antibacterial activity of Ginko biloba GKB from glycerin nanocapsules and nanoemulsions. GKB was formulated as spray formulation for topical application using ethyl alcohol 95%/glycerol/water based formulations. GKB spray was evaluated for their particle size distribution, pH, content uniformity, content per spray, in vitro release and antifungal activity. The antifungal activity was determined by Agar welldiffusion method. The formulae were tested for their skin permeation and the stability of the formulations. The results showed uniform formulae with nano-sized particles, pH compatible with the topical formulation and higher drug content. Diffusion studies of the optimized formulations through the abdominal rabbit skin showed higher penetrated drug over a period of 24 h. Stability studies indicated that formulations were stable. Skin irritation studies confirmed the compatibility of spray formulae with skin. Agar well-diffusion method showed that GKB was effective compared with fluconazole. The inhibition zones for all formulae were significant as compared with standard fluconazole. The results obtained showed that the topical spray formulation could be a promising and innovative therapeutic system as topical antifungal for the transdermal administration of GKB. The developed formulation can be used for delivery from spray formulation. This study proved the local activity of GKB as antifungal drugs.

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Section: Ex Vivo Skin Permeationsupporting

confidence: 91%

A Novel Topical Spray Formulation for Ginkgo Bioloba for Antifungal Activity

Aah¹

2016

J Nanomed Nanotechnol

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“…Cubosomal dispersion of different formulations (equivalent to 3 mg of SIL) was added to glass cylinders (6 cm length and 2.5 cm internal diameter) tightly covered from one end with the dialysis membrane with molecular weight cut-off of 12,000 Da, which was soaked in the receptor medium overnight. The loaded cylinders were fixed at the shafts of the USP dissolution tester apparatus (Abdelrahman et al., 2015 ). The release medium was 70 mL PBS pH 4.5 to mimic the pH of the vaginal environment.…”

Section: Methodsmentioning

confidence: 99%

“…Moreover, a check point analysis was implemented to verify the reliability and validity of the generated mathematical model for dependent response predictions. The response surfaces were generated and the overlaying region of an overall desired response was corresponding to the optimum region where the cubosomal dispersions with appropriated properties can be obtained (Abdelrahman et al., 2015 ). Finally, desirability values were calculated and compared for the prediction of the formulation with the optimized characteristics.…”

Section: Methodsmentioning

confidence: 99%

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Novel in situ gelling vaginal sponges of sildenafil citrate-based cubosomes for uterine targeting

et al. 2018

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Sildenafil citrate (SIL), a type 5-specific phosphodiesterase inhibitor, demonstrates valuable results in the management of infertility in women; however, the absence of vaginal dosage form in addition to the associated oral adverse effects minimize its clinical performance. The present study is concerned with SIL uterine targeting following intravaginal administration via optimization of cubosomal in situ gelling sponges (CIS). An emulsification method was employed for preparation of cubosomal dispersions incorporating glyceryl monooleate as a lipid phase and poloxamer 407 as a surfactant with or without polyvinyl alcohol as a stabilizer. Cubosomes were estimated regarding entrapment efficiency (EE%), particle size, and in vitro drug release. Chitosan (2% w/w) was incorporated into the optimum formulation and then lyophilized into small sponges. For the CIS, in vivo histopathological and pharmacokinetic studies were conducted on female Wistar rats and compared with intravaginal free SIL sponges (FIS) and oral SIL solution. SIL-loaded cubosomes showed EE% ranging between 32.15 and 72.01%, particle size in the range of 150.81–446.02 nm and sustained drug release over 8 h. Histopathological study revealed a significant enlargement in endometrial thickness with congestion and dilatation of endometrial blood vessels in intravaginal CIS compared to intravaginal FIS and oral-treated groups. The pharmacokinetic study demonstrated higher AUC0–∞ and Cmax with oral administration compared to intravaginal CIS or intravaginal FIS indicating potential involvement of first uterine pass effect after intravaginal administration. Finally, intravaginal CIS could be considered as a promising platform for SIL uterine targeting with minimized systemic exposure and side effects.

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“…Moreover, the AUC (0-1) and MRT (0)(1) in the brain after I.N administration of 99m Tc-R7 were significantly higher value compared to I.V administration of 99m Tc-ZT solution (23.28 and 0.89 h%/g) and (36.38 and 9.35 h), respectively (p50.05). This could be explained by the high capability of the lipid nanovesicles to permeate the nasal membrane (Salama et al, 2012;Abdelrahman et al, 2015). This suggests that the nasal route is considered as preferential route for brain targeting than I.V.…”

Section: Animal Studymentioning

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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Investigating the cubosomal ability for transnasal brain targeting: In vitro optimization, ex vivo permeation and in vivo biodistribution

Cited by 75 publications

References 51 publications

A Novel Topical Spray Formulation for Ginkgo Bioloba for Antifungal Activity

A Novel Topical Spray Formulation for Ginkgo Bioloba for Antifungal Activity

Novel in situ gelling vaginal sponges of sildenafil citrate-based cubosomes for uterine targeting

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

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