Occupational safety assessment of biogenic urea nanofertilisers using in vitro pulmonary, and in vivo ocular models.

Nanomaterials (NMs) are now gaining popularity to be used in agriculture as fertilisers to reduce the dose of conventional fertilisers and enhance nutrient use efficiency. Urea has found its application as a conventional nitrogenous fertiliser since long, however, the nutrient use efficiency of the bulk form of urea is low due to issues related to ammonia volatilisation. This study proposes a biogenic synthesis route to develop urea nanoparticles that can be used as nano-fertiliser for better uptake and hence improved nutrient efficiency. Large scale production and widespread application of these nano-fertilisers to the agricultural fields will enhance the direct exposure to workers and farmers. Therefore, the occupational safety evaluation becomes critical. In this study, we report a new method for synthesis of urea nanoparticles (TNU, absolute size: 12.14 ± 7.79 nm) followed by nano-safety evaluation. Herein, the pulmonary and ocular compatibilities of TNU were investigated in vitro and in vivo respectively. The assay for cellular mitochondrial activity was carried out on human lung fibroblasts (WI-38) under varied TNU exposure concentrations up to 72 h. The acute biocompatibility effect, ocular irritation and sub-lethal effects were measured on New Zealand Rabbit. The results show that TNU do not exhibit any cytotoxicity and detrimental cell mitochondrial activity up to the highest tested concentration of 1000 µg/mL and 72 h of testing. The animal experiment results also show that neither acute nor sub-lethal toxic effects can be detected after TNU ocular instillation up to 21 days when tested up to environmentally relevant concentration of 15 µg/mL. These results suggest the occupational safety of biogenic urea nanoparticles and support its application as nanofertiliser.

A multifunctional therapeutic approach: Synthesis, biological evaluation, crystal structure and molecular docking of diversified 1H-pyrazolo[3,4-b]pyridine derivatives against Alzheimer's disease.

2-(piperazin-1-yl)N-(1H-pyrazolo[3,4-b]pyridin-3-yl)acetamides are described as a new class of selective and potent acetylcholinesterase (AChE) inhibitors and amyloid ß aggregation inhibitors. Formation of synthesized compounds (P1P9) was justified via H1 NMR, C13 NMR, mass spectra and single crystal X-Ray diffraction study. All compounds were evaluated for their acetylcholinesterase and butyrylcholinesterase inhibitory activity, inhibition of self-mediated Aß aggregation and Cu(II)-mediated Aß aggregation. Also, docking study carried out was in concordance with in vitro results. The most potent molecule amongst the derivatives exhibited excellent anti-AChE activity (IC50 = 4.8 nM). Kinetic study of P3 suggested it to be a mixed type inhibitor. In vitro study revealed that all the compounds are capable of inhibiting self-induced ß-amyloid (Aß) aggregation with the highest inhibition percentage to be 81.65%. Potency of P1 and P3 to inhibit self-induced Aß1-42 aggregation was ascertained by TEM analysis. Compounds were also evaluated for their Aß disaggregation, antioxidation, metal-chelation activity.