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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

Histopathology of the kidney tissue(10×)2/weeks post-exposure to ZAL (A),ZA (B) and vehicle control (C). G, glomerulus; T, renal tubule. The kidney tissue was stained with H&E, showing preserved glomerular and tubular structure in A and B, similar to the finding in the control group (C). Microscopic appearance of brain cortical region after H&E stain.
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Fig4: Histopathology of the kidney tissue(10×)2/weeks post-exposure to ZAL (A),ZA (B) and vehicle control (C). G, glomerulus; T, renal tubule. The kidney tissue was stained with H&E, showing preserved glomerular and tubular structure in A and B, similar to the finding in the control group (C). Microscopic appearance of brain cortical region after H&E stain.

Mentions: Histological examination of the liver, spleen, kidney and brain stained with H&E stain in the control and treated animals showed no remarkable lesions that could be attributed to the effect of a single dose of ZAL or ZA (Figures 2, 3, 4, 5 and 6). Hepatic lobular array from the treated group and control was well maintained, central vein (CV) located at the centre surrounded by portal triad (PT) and drained by sinusoids (S) (Figure 2). The splenic architecture of the high-dose treated groups showed well-maintained capsule, clearly demarcated white and red pulp and with adjoining trabecular all over the tissues. These histologic features were similar to those of the vehicle control group (Figure 3). The histology of the kidneys showed no pathologic changes in the treated groups when compared to control (Figure 4). The cerebral cortical layers were well delineated in the brain of vehicle-administered group Figure 5C, so is the substantia nigral region in Figure 6C. Findings in the brain of ZAL- and ZA-treated group were remarkably similar to those in the control group (Figures 5A, B and 6A, B). Oral administration of 2,000 mg/kg of layered hydroxide nanocomposite with and without levodopa does not alter the microscopic structure of the vital organs.Figure 2


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)

Histopathology of the kidney tissue(10×)2/weeks post-exposure to ZAL (A),ZA (B) and vehicle control (C). G, glomerulus; T, renal tubule. The kidney tissue was stained with H&E, showing preserved glomerular and tubular structure in A and B, similar to the finding in the control group (C). Microscopic appearance of brain cortical region after H&E stain.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig4: Histopathology of the kidney tissue(10×)2/weeks post-exposure to ZAL (A),ZA (B) and vehicle control (C). G, glomerulus; T, renal tubule. The kidney tissue was stained with H&E, showing preserved glomerular and tubular structure in A and B, similar to the finding in the control group (C). Microscopic appearance of brain cortical region after H&E stain.
Mentions: Histological examination of the liver, spleen, kidney and brain stained with H&E stain in the control and treated animals showed no remarkable lesions that could be attributed to the effect of a single dose of ZAL or ZA (Figures 2, 3, 4, 5 and 6). Hepatic lobular array from the treated group and control was well maintained, central vein (CV) located at the centre surrounded by portal triad (PT) and drained by sinusoids (S) (Figure 2). The splenic architecture of the high-dose treated groups showed well-maintained capsule, clearly demarcated white and red pulp and with adjoining trabecular all over the tissues. These histologic features were similar to those of the vehicle control group (Figure 3). The histology of the kidneys showed no pathologic changes in the treated groups when compared to control (Figure 4). The cerebral cortical layers were well delineated in the brain of vehicle-administered group Figure 5C, so is the substantia nigral region in Figure 6C. Findings in the brain of ZAL- and ZA-treated group were remarkably similar to those in the control group (Figures 5A, B and 6A, B). Oral administration of 2,000 mg/kg of layered hydroxide nanocomposite with and without levodopa does not alter the microscopic structure of the vital organs.Figure 2

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