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Novel piperine-loaded Tween-integrated monoolein cubosomes as brain-targeted oral nanomedicine in Alzheimer's disease: pharmaceutical, biological, and toxicological studies.

Elnaggar YS, Etman SM, Abdelmonsif DA, Abdallah OY - Int J Nanomedicine (2015)

Bottom Line: In vivo studies revealed T-cubs potential to significantly enhance PIP cognitive effect and even restore cognitive function to the normal level.Superiority of T-cubs over others suggested brain-targeting effect of Tween.Novel oral nanoparticles elaborated possess promising in vitro and in vivo characteristics with high safety for effective chronic treatment of AD.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt.

ABSTRACT
Alzheimer's disease (AD) is one of the most patient devastating central nervous system diseases with no curative therapy. An effective oral therapy with brain-targeting potential is required that is hampered by blood-brain barrier. Piperine (PIP) is a natural alkaloid with memory enhancing potentials. Oral PIP delivery suffers from its hydrophobicity and first-pass metabolism. In this study, novel Tween-modified monoolein cubosomes (T-cubs) were elaborated as bioactive nanocarriers for brain-targeted oral delivery of PIP. Seven liquid crystalline nanoparticles (cubosomes) were prepared testing different bioactive surfactants (Tween 80, poloxamer, and Cremophor). Full in vitro characterization was carried out based on particle size, zeta potential, polydispersity index, entrapment efficiency, and in vitro release. Morphological examination and structure elucidation were performed using transmission and polarizing microscopes. Sporadic dementia of Alzheimer's type was induced in 42 male Wistar rats on which full behavioral and biochemical testing was conducted. Brain toxicity was assessed based on Caspase-3 assay for apoptosis and tumor necrosis factor-α for inflammation. Liver and kidney toxicity studies were conducted as well. Among others, T-cubs exhibited optimum particle size (167.00±10.49 nm), polydispersity index (0.18±0.01), and zeta potential (-34.60±0.47 mv) with high entrapment efficiency (86.67%±0.62%). Cubs could significantly sustain PIP in vitro release. In vivo studies revealed T-cubs potential to significantly enhance PIP cognitive effect and even restore cognitive function to the normal level. Superiority of T-cubs over others suggested brain-targeting effect of Tween. Toxicological studies contended safety of cubs on kidney, liver, and even brain. T-cubs exhibited potential anti-inflammatory and anti-apoptotic activity of loaded PIP, indicating potential to stop AD progression that was first suggested in this article. Novel oral nanoparticles elaborated possess promising in vitro and in vivo characteristics with high safety for effective chronic treatment of AD.

No MeSH data available.


Related in: MedlinePlus

In vitro release profiles of PIP aqueous suspension and PIP-loaded cubosomes in phosphate buffer (pH 7.4) at 37°C.Abbreviations: PIP, piperine; T-cubs, Tween-modified monoolein cubosomes; S mix cubs, surfactant mixture cubosomes; Cubs, cubosomes.
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f1-ijn-10-5459: In vitro release profiles of PIP aqueous suspension and PIP-loaded cubosomes in phosphate buffer (pH 7.4) at 37°C.Abbreviations: PIP, piperine; T-cubs, Tween-modified monoolein cubosomes; S mix cubs, surfactant mixture cubosomes; Cubs, cubosomes.

Mentions: As shown in Figure 1, the release of PIP for all cubs formulations followed a biphasic pattern with initial burst release of approximately 21% of the drug released in the first hour then the drug release was sustained with only 45% released after 6 hours. This is compared with nearly 80% release from the PIP suspension in the first 2 hours.


Novel piperine-loaded Tween-integrated monoolein cubosomes as brain-targeted oral nanomedicine in Alzheimer's disease: pharmaceutical, biological, and toxicological studies.

Elnaggar YS, Etman SM, Abdelmonsif DA, Abdallah OY - Int J Nanomedicine (2015)

In vitro release profiles of PIP aqueous suspension and PIP-loaded cubosomes in phosphate buffer (pH 7.4) at 37°C.Abbreviations: PIP, piperine; T-cubs, Tween-modified monoolein cubosomes; S mix cubs, surfactant mixture cubosomes; Cubs, cubosomes.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4556290&req=5

f1-ijn-10-5459: In vitro release profiles of PIP aqueous suspension and PIP-loaded cubosomes in phosphate buffer (pH 7.4) at 37°C.Abbreviations: PIP, piperine; T-cubs, Tween-modified monoolein cubosomes; S mix cubs, surfactant mixture cubosomes; Cubs, cubosomes.
Mentions: As shown in Figure 1, the release of PIP for all cubs formulations followed a biphasic pattern with initial burst release of approximately 21% of the drug released in the first hour then the drug release was sustained with only 45% released after 6 hours. This is compared with nearly 80% release from the PIP suspension in the first 2 hours.

Bottom Line: In vivo studies revealed T-cubs potential to significantly enhance PIP cognitive effect and even restore cognitive function to the normal level.Superiority of T-cubs over others suggested brain-targeting effect of Tween.Novel oral nanoparticles elaborated possess promising in vitro and in vivo characteristics with high safety for effective chronic treatment of AD.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt.

ABSTRACT
Alzheimer's disease (AD) is one of the most patient devastating central nervous system diseases with no curative therapy. An effective oral therapy with brain-targeting potential is required that is hampered by blood-brain barrier. Piperine (PIP) is a natural alkaloid with memory enhancing potentials. Oral PIP delivery suffers from its hydrophobicity and first-pass metabolism. In this study, novel Tween-modified monoolein cubosomes (T-cubs) were elaborated as bioactive nanocarriers for brain-targeted oral delivery of PIP. Seven liquid crystalline nanoparticles (cubosomes) were prepared testing different bioactive surfactants (Tween 80, poloxamer, and Cremophor). Full in vitro characterization was carried out based on particle size, zeta potential, polydispersity index, entrapment efficiency, and in vitro release. Morphological examination and structure elucidation were performed using transmission and polarizing microscopes. Sporadic dementia of Alzheimer's type was induced in 42 male Wistar rats on which full behavioral and biochemical testing was conducted. Brain toxicity was assessed based on Caspase-3 assay for apoptosis and tumor necrosis factor-α for inflammation. Liver and kidney toxicity studies were conducted as well. Among others, T-cubs exhibited optimum particle size (167.00±10.49 nm), polydispersity index (0.18±0.01), and zeta potential (-34.60±0.47 mv) with high entrapment efficiency (86.67%±0.62%). Cubs could significantly sustain PIP in vitro release. In vivo studies revealed T-cubs potential to significantly enhance PIP cognitive effect and even restore cognitive function to the normal level. Superiority of T-cubs over others suggested brain-targeting effect of Tween. Toxicological studies contended safety of cubs on kidney, liver, and even brain. T-cubs exhibited potential anti-inflammatory and anti-apoptotic activity of loaded PIP, indicating potential to stop AD progression that was first suggested in this article. Novel oral nanoparticles elaborated possess promising in vitro and in vivo characteristics with high safety for effective chronic treatment of AD.

No MeSH data available.


Related in: MedlinePlus