Advances in controlled release pesticide formulations: Prospects to safer integrated pest management and sustainable agriculture.

As the world is striving hard towards sustainable agricultural practices for a better tomorrow, one of the primary focuses is on effective pest management for enhanced crop productivity. Despite newer and potent chemicals as pesticides, there are still substantial crop losses, and if by any means this loss can be tackled; it will alleviate unwanted excessive use of chemical pesticides. Scientific surveys have already established that pesticides are not being utilized by the crops completely rather a significant amount remains unused due to various limiting factors such as leaching and bioconversion, etc., resulting in an adverse effect on human health and ecosystems. Concerted efforts from scientific diaspora toward newer and innovative strategies are already showing promise, and one such viable approach is controlled release systems (CRS) of pesticides. Moreover, to bring these smart formulations within the domain of current pesticide regulatory framework is still under debate. It is thus, paramount to discuss the pros and cons of this new technology vis-à-vis the conventional agrarian methods. This review deliberates on the developmental updates in this innovative field from the past decades and also appraises the challenges encumbered. Additionally, critical information and the foreseeable research gaps in this emerging area are highlighted.

Accelerated and scarless wound repair by a multicomponent hydrogel through simultaneous activation of multiple pathways.

Scarless healing of injury remains a clinical challenge because of its complicated and overlapping phases of inflammation, clearing, and regeneration. Curcumin has been already established as a potential wound healing agent for normal and diabetic-impaired wounds. Herein, the question has been addressed whether a well-known antioxidant cerium oxide nanoparticle (CNP) can potentiate the activity of curcumin to promote a cellular program for scarless healing. In this study, we have developed a biocompatible poly (acrylamide) hydrogel (PAGE)-based dressing material comprising of CNP and curcumin (ACC) and tested its wound healing activity in an animal model of acute wound. Characterization of the CNP- and curcumin-entrapped hydrogel dressing (ACC) demonstrated high loading efficiency and sustained release of curcumin. In a full-thickness acute wound healing model of rat, a single application of ACC dressing demonstrated higher wound healing efficacy (78%) and negligible scarring compared to dressings containing only curcumin or CNP in 7 days. Enhanced cell proliferation, higher collagen content, advanced wound maturity, re-epithelialization, and granulation tissue formation were observed using the combination of curcumin and CNP (ACC). Study of cellular mechanisms identified MCP-1 and TGF-ß as the key drivers of differential and accelerated healing observed in the ACC group. These, coupled with the upregulation of growth-related signaling pathways (HER2/ErbB2, TGF-ß-Smad2/3, MAPK/ERK, AKT, and VEGF), promoted almost scarless healing in animals treated with ACC. The optimized combination of curcumin and CNP used in our study shows distinct advantage and can be a better agent for complete wound healing.

Curcumin loaded selenium nanoparticles synergize the anticancer potential of doxorubicin contained in self-assembled, cell receptor targeted nanoparticles.

Doxorubicin (DOX) has been extensively used to treat a wide range of cancers in free and nanotized form. Nanotization of DOX has alleviated its toxicity and efflux-mediated resistance. However, frequent upregulation of anti-apoptotic pathways, chemotherapy-enhanced inflammation, and epithelial-mesenchymal transition (EMT), present additional aspects of cellular DOX résistance. Nanoparticle-mediated combination therapy of DOX with additional anticancer agents is expected to offer greater therapeutic benefit by alleviating the overall drug résistance. We synthesized CD44-targeted DOX loaded nanoparticles (PSHA-DOXNPs) and evaluated their anticancer efficacy in combination with curcumin loaded selenium nanoparticles (Se-Cur NPs), previously developed by our group (Kumari et al., 2017). Combination of these nanoparticles (NPs) increased ROS level, decreased mitochondrial membrane potential, induced cell cycle arrest and apoptosis in HCT116 cells. This combination decreased the expressions of NFκB, Phospho-NFκB, EMT-metastasis-associated proteins (Snail, Vimentin, N-cadherin, CD44, MMP-2 and MMP-9), autophagy-associated proteins (Beclin-1 and LC-3BII), as well as anti-apoptotic protein Bcl-2, increased the expression of pro-apoptotic protein Bax, and increased cyt c release, which indicated decrease in inflammation, metastasis, and autophagy with increase in apoptosis. Moreover, the combination of NPs decreased tumor burden and increased survival of Ehrlich's ascites carcinoma (EAC)-bearing mice.

Zinc Oxide Nanoparticle Induces Microglial Death by NADPH-Oxidase-Independent Reactive Oxygen Species as well as Energy Depletion.

Zinc oxide nanoparticle (ZnO-NP) is one of the most widely used engineered nanoparticles. Upon exposure, nanoparticle can eventually reach the brain through various routes, interact with different brain cells, and alter their activity. Microglia is the fastest glial cell to respond to any toxic insult. Nanoparticle exposure can activate microglia and induce neuroinflammation. Simultaneous to activation, microglial death can exacerbate the scenario. Therefore, we focused on studying the effect of ZnO-NP on microglia and finding out the pathway involved in the microglial death. The present study showed that the 24 h inhibitory concentration 50 (IC50) of ZnO-NP for microglia is 6.6 µg/ml. Early events following ZnO-NP exposure involved increase in intracellular calcium level as well as reactive oxygen species (ROS). Neither of NADPH oxidase inhibitors, apocynin, (APO) and diphenyleneiodonium chloride (DPIC) were able to reduce the ROS level and rescue microglia from ZnO-NP toxicity. In contrary, N-acetyl cysteine (NAC) showed opposite effect. Exogenous supplementation of superoxide dismutase (SOD) reduced ROS significantly even beyond control level but partially rescued microglial viability. Interestingly, pyruvate supplementation rescued microglia near to control level. Following 10 h of ZnO-NP exposure, intracellular ATP level was measured to be almost 50 % to the control. ZnO-NP-induced ROS as well as ATP depletion both disturbed mitochondrial membrane potential and subsequently triggered the apoptotic pathway. The level of apoptosis-inducing proteins was measured by western blot analysis and found to be upregulated. Taken together, we have deciphered that ZnO-NP induced microglial apoptosis by NADPH oxidase-independent ROS as well as ATP depletion.

General Reagent Free Route to pH Responsive Polyacryloyl Hydrazide Capped Metal Nanogels for Synergistic Anticancer Therapeutics.

Herewith, we report a facile synthesis of pH responsive polyacryloyl hydrazide (PAH) capped silver (Ag) or gold (Au) nanogels for anticancer therapeutic applications. A cost-effective instant synthesis of PAH-Ag or PAH-Au nanoparticles (NPs) possessing controllable particle diameter and narrow size distribution was accomplished by adding AgNO3 or AuCl to the aqueous solution of PAH under ambient conditions without using any additional reagent. PAH possessing carbonyl hydrazide pendant functionality served as both reducing and capping agent to produce and stabilize the NPs. The stability analysis by UV-vis, dynamic light scattering, and transmission electron microscopy techniques suggested that these NPs may be stored in a refrigerator for at least up to 2 weeks with negligible change in conformation. The average hydrodynamic size of PAH-Ag NPs synthesized using 0.2 mmol/L AgNO3 changed from 122 to 226 nm on changing the pH of the medium from 5.4 to 7.4, which is a characteristic property of pH responsive nanogel. Camptothecin (CPT) with adequate loading efficiency (6.3%) was encapsulated in the PAH-Ag nanogels. Under pH 5.4 conditions, these nanogels released 78% of the originally loaded CPT over a period of 70 h. The antiproliferative potential of PAH-Ag-CPT nanogels (at [CPT]=0.6 µg/mL) against MCF-7 breast adeno-carcinoma cells were ∼350% higher compared to that of the free CPT as evidenced by high cellular internalization of these nanogels. Induction of apoptosis in MCF-7 breast adeno-carcinoma cells by PAH-Ag-CPT nanogels was evidenced by accumulation of late apoptotic cell population. Drug along with the PAH-Ag NPs were also encapsulated in a pH responsive hydrogel through in situ gelation at room temperature using acrylic acid as the cross-linker. The resulting hydrogel released quantitative amounts of both drug and PAH-Ag NPs over a period of 16 h. The simplicity of synthesis and ease of drug loading with efficient release render these NPs a viable candidate for various biomedical applications, and moreover this synthetic procedure may be extended to other metal NPs.