Toxicity evaluation of zinc aluminium levodopa nanocomposite via oral route in repeated dose study

Abstract

Nanotechnology, through nanomedicine, allowed drugs to be manipulated into nanoscale sizes for delivery to the different parts of the body, at the same time, retaining the valuable pharmacological properties of the drugs. However, efficient drug delivery and excellent release potential of these delivery systems may be hindered by possible untoward side effects. In this study, the sub-acute toxicity of oral zinc aluminium nanocomposite with and without levodopa was assessed using the Organization for Economic Co-operation and Development guidelines. No sign or symptom of toxicity was observed in orally treated rats with the nanocomposite at 5 and 500 mg/kg concentrations. Body weight gain, feeding, water intake, general survival and organosomatic index were not significantly different between control and treatment groups. Aspartate aminotransferase (AST) in 500 mg/kg levodopa nanocomposite (169 ± 30 U/L), 5 mg/kg levodopa nanocomposite (172 ± 49 U/L), and 500 mg/kg layered double hydroxides (LDH) nanocomposite (175 ± 25 U/L) were notably elevated compared to controls (143 ± 05 U/L); but the difference were not significant (p > 0.05). However, the differences in aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio of 500 mg/kg levodopa nanocomposite (0.32 ± 0.12) and 500 mg/kg LDH nanocomposite (0.34 ± 0.12) were statistically significant (p < 0.05) compared to the control (0.51 ± 0.07). Histology of the liver, spleen and brain was found to be of similar morphology in both control and experimental groups. The kidneys of 500-mg/kg-treated rats with levodopa nanocomposite and LDH nanocomposite were found to have slight inflammatory changes, notably leukocyte infiltration around the glomeruli. The ultra-structure of the neurons from the substantia nigra of nanocomposite-exposed group was similar to those receiving only normal saline. The observed result has suggested possible liver and renal toxicity in orally administered levodopa intercalated nanocomposite; it is also dose-dependent that needs further assessment.

Inorganic nanolayers: structure, preparation, and&nbsp;biomedical applications

“…In addition, the liver, spleen, and brain histology was similar with the control group. 195 In vivo biocompatibility is the most important characteristic of any material considered for biomedical application. The aforementioned in vivo biocompatibility studies are highly encouraging, but there is still need for further in vivo studies on LDHs in order to establish that they are safe for biomedical applications.…”

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

“…The tissues were obtained from the above-mentioned animal groups as well from our previous sub-acute toxicity study of the same compounds (Table 2) [10]. Tissues of the liver, spleen, kidney and brain were taken out and thawed.…”

“…Pharmaceutical formulations including nanodelivery systems (NDSs) are taken into the human body through any of the several routes of drug administration [10,11]. The route of exposure may influence the distribution and bioavailability, especially transport across biological barriers like the brain [11].…”

“…Further coating of ZAL with polysorbate-80 (Tween-80) showed an improved release profile and a better cell viability ([23]. Repeated dose of the same nanocomposite in animal study showed slight liver and renal derangement [10]. However, establishing the entire toxicological profile using an animal model, acute and chronic toxicity assessment is also indispensable.…”

Nanodelivery systems and stabilized solid-drug nanoparticles for orally administered medicine: current landscape

“…The data clearly signified the necessity for additional and more detailed examination of the acute hepatic and renal adverse effects after oral dosing with the nanocomposite. 87 It is understood that excessively generated reactive oxygen species are associated with age-related neurodegenerative disease. In a recent study, the scavenging potential of reactive oxygen species in the brain was investigated following oral administration of RNPO (40 nm), prepared by self-assembly of redox polymers possessing antioxidant nitroxide radicals in a male senescence-accelerated-prone mouse model.…”