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Acute oral toxicity and biodistribution study of zinc-aluminium-levodopa nanocomposite.

Kura AU, Saifullah B, Cheah PS, Hussein MZ, Azmi N, Fakurazi S - Nanoscale Res Lett (2015)

Bottom Line: The oral administration of ZAL and ZA at a limit dose of 2,000 mg/kg produced neither mortality nor acute toxic signs throughout 14 days of the observation.In summary, findings of acute toxicity tests in this study suggest that zinc-aluminium nanocomposite intercalated with and the un-intercalated were safe when administered orally in animal models for short periods of time.It also highlighted the potential distribution ability of Tween-80 coated nanocomposite after oral administration.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Vaccines and Immunotherapeutics, Institute of Bioscience, Universiti Putra Malaysia, 43400 Selangor, Malaysia.

ABSTRACT
Layered double hydroxide (LDH) is an inorganic-organic nano-layered material that harbours drug between its two-layered sheets, forming a sandwich-like structure. It is attracting a great deal of attention as an alternative drug delivery (nanodelivery) system in the field of pharmacology due to their relative low toxic potential. The production of these nanodelivery systems, aimed at improving human health through decrease toxicity, targeted delivery of the active compound to areas of interest with sustained release ability. In this study, we administered zinc-aluminium-LDH-levodopa nanocomposite (ZAL) and zinc-aluminium nanocomposite (ZA) to Sprague Dawley rats to evaluate for acute oral toxicity following OECD guidelines. The oral administration of ZAL and ZA at a limit dose of 2,000 mg/kg produced neither mortality nor acute toxic signs throughout 14 days of the observation. The percentage of body weight gain of the animals showed no significant difference between control and treatment groups. Animal from the two treated groups gained weight continuously over the study period, which was shown to be significantly higher than the weight at the beginning of the study (P < 0.05). Biochemical analysis of animal serum showed no significant difference between rats treated with ZAL, ZA and controls. There was no gross lesion or histopathological changes observed in vital organs of the rats. The results suggested that ZAL and ZA at 2,000 mg/kg body weight in rats do not induce acute toxicity in the animals. Elemental analysis of tissues of treated animals demonstrated the wider distribution of the nanocomposite including the brain. In summary, findings of acute toxicity tests in this study suggest that zinc-aluminium nanocomposite intercalated with and the un-intercalated were safe when administered orally in animal models for short periods of time. It also highlighted the potential distribution ability of Tween-80 coated nanocomposite after oral administration.

No MeSH data available.


Related in: MedlinePlus

Graph showing nanocomposite distribution after repeated doses in a 28-day oral toxicity study. Graph showing nanocomposite distribution in tissues of rats after repeated doses in a 28-day oral toxicity study. Zinc distribution in rats after repeated dose of Tween-80-coated zinc-aluminium-levodopa layered double hydroxide nanocomposite ( ZAL) over 28-day period. B = 500 mg/kg of ZAL, D = 5 mg/kg of ZAL, J = 100 mL/kg of PBS (control group). No significant difference found between control and treated group in any of tissues analysed P > 0.05.
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Fig9: Graph showing nanocomposite distribution after repeated doses in a 28-day oral toxicity study. Graph showing nanocomposite distribution in tissues of rats after repeated doses in a 28-day oral toxicity study. Zinc distribution in rats after repeated dose of Tween-80-coated zinc-aluminium-levodopa layered double hydroxide nanocomposite ( ZAL) over 28-day period. B = 500 mg/kg of ZAL, D = 5 mg/kg of ZAL, J = 100 mL/kg of PBS (control group). No significant difference found between control and treated group in any of tissues analysed P > 0.05.

Mentions: The Tween-80-coated nanocomposite showed a wider distribution after oral administration from both repeated and single-dose application, respectively (Figures 8 and 9). Reasonable amount of zinc element was found in the liver, kidney, blood and brain of the treated rats compared to the control.Figure 8


Acute oral toxicity and biodistribution study of zinc-aluminium-levodopa nanocomposite.

Kura AU, Saifullah B, Cheah PS, Hussein MZ, Azmi N, Fakurazi S - Nanoscale Res Lett (2015)

Graph showing nanocomposite distribution after repeated doses in a 28-day oral toxicity study. Graph showing nanocomposite distribution in tissues of rats after repeated doses in a 28-day oral toxicity study. Zinc distribution in rats after repeated dose of Tween-80-coated zinc-aluminium-levodopa layered double hydroxide nanocomposite ( ZAL) over 28-day period. B = 500 mg/kg of ZAL, D = 5 mg/kg of ZAL, J = 100 mL/kg of PBS (control group). No significant difference found between control and treated group in any of tissues analysed P > 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4385219&req=5

Fig9: Graph showing nanocomposite distribution after repeated doses in a 28-day oral toxicity study. Graph showing nanocomposite distribution in tissues of rats after repeated doses in a 28-day oral toxicity study. Zinc distribution in rats after repeated dose of Tween-80-coated zinc-aluminium-levodopa layered double hydroxide nanocomposite ( ZAL) over 28-day period. B = 500 mg/kg of ZAL, D = 5 mg/kg of ZAL, J = 100 mL/kg of PBS (control group). No significant difference found between control and treated group in any of tissues analysed P > 0.05.
Mentions: The Tween-80-coated nanocomposite showed a wider distribution after oral administration from both repeated and single-dose application, respectively (Figures 8 and 9). Reasonable amount of zinc element was found in the liver, kidney, blood and brain of the treated rats compared to the control.Figure 8

Bottom Line: The oral administration of ZAL and ZA at a limit dose of 2,000 mg/kg produced neither mortality nor acute toxic signs throughout 14 days of the observation.In summary, findings of acute toxicity tests in this study suggest that zinc-aluminium nanocomposite intercalated with and the un-intercalated were safe when administered orally in animal models for short periods of time.It also highlighted the potential distribution ability of Tween-80 coated nanocomposite after oral administration.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Vaccines and Immunotherapeutics, Institute of Bioscience, Universiti Putra Malaysia, 43400 Selangor, Malaysia.

ABSTRACT
Layered double hydroxide (LDH) is an inorganic-organic nano-layered material that harbours drug between its two-layered sheets, forming a sandwich-like structure. It is attracting a great deal of attention as an alternative drug delivery (nanodelivery) system in the field of pharmacology due to their relative low toxic potential. The production of these nanodelivery systems, aimed at improving human health through decrease toxicity, targeted delivery of the active compound to areas of interest with sustained release ability. In this study, we administered zinc-aluminium-LDH-levodopa nanocomposite (ZAL) and zinc-aluminium nanocomposite (ZA) to Sprague Dawley rats to evaluate for acute oral toxicity following OECD guidelines. The oral administration of ZAL and ZA at a limit dose of 2,000 mg/kg produced neither mortality nor acute toxic signs throughout 14 days of the observation. The percentage of body weight gain of the animals showed no significant difference between control and treatment groups. Animal from the two treated groups gained weight continuously over the study period, which was shown to be significantly higher than the weight at the beginning of the study (P < 0.05). Biochemical analysis of animal serum showed no significant difference between rats treated with ZAL, ZA and controls. There was no gross lesion or histopathological changes observed in vital organs of the rats. The results suggested that ZAL and ZA at 2,000 mg/kg body weight in rats do not induce acute toxicity in the animals. Elemental analysis of tissues of treated animals demonstrated the wider distribution of the nanocomposite including the brain. In summary, findings of acute toxicity tests in this study suggest that zinc-aluminium nanocomposite intercalated with and the un-intercalated were safe when administered orally in animal models for short periods of time. It also highlighted the potential distribution ability of Tween-80 coated nanocomposite after oral administration.

No MeSH data available.


Related in: MedlinePlus