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Acute kidney injury (AKI) is a progressive renal complication which significantly affects the patient's life with huge economic burden. Untreated acute kidney injury eventually progresses to a chronic form and end-stage renal disease. Although significant breakthroughs have been made in recent years, there are still no effective pharmacological therapies for the treatment of acute kidney injury. Toll-like receptor 4 (TLR4) is a well-characterized pattern recognition receptor, and increasing evidence has shown that TLR4 mediated inflammatory response plays a pivotal role in the pathogenesis of acute kidney injury. The expression of TLR4 has been seen in resident renal cells, including podocytes, mesangial cells, tubular epithelial cells and endothelial cells. Activation of TLR4 signaling regulates the transcription of numerous pro-inflammatory cytokines and chemokines, resulting in renal inflammation. Therefore, targeting TLR4 and its downstream effectors could serve as an effective therapeutic intervention to prevent renal inflammation and subsequent kidney damage. For the first time, this review summarizes the literature on acute kidney injury from the perspective of TLR4 from year 2010 to 2020. In the current review, the role of TLR4 signaling pathway in AKI with preclinical evidence is discussed. Furthermore, we have highlighted several compounds of natural and synthetic origin, which have the potential to avert the renal TLR4 signaling in preclinical AKI models and have shown protection against AKI. This scientific review provides new ideas for targeting TLR4 in the treatment of AKI and provides strategies for the drug development against AKI., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The diagnosis and treatment of neurological ailments always remain an utmost challenge for research fraternity due to the presence of BBB. The intranasal route appeared as an attractive and alternative route for brain targeting of therapeutics without the intrusion of BBB and GI exposure. This route directly and effectively delivers the therapeutics to different regions of the brain via olfactory and trigeminal nerve pathways. However, shorter drug retention time and mucociliary clearance curtail the efficiency of the intranasal route. The in situ mucoadhesive gel overthrow the limitations of direct nose-to-brain delivery by not only enhancing nasal residence time but also minimizing the mucociliary clearance and enzymatic degradation. This delivery system further improves the nasal absorption as well as bioavailability of drugs in the brain. The in situ mucoadhesive gel is a controlled and sustained release system that facilitates the absorption of various proteins, peptides and other larger lipophilic and hydrophilic moieties. Owing to multiple benefits, in situ gelling system has been widely explored to target the brain via nasal route. However, very few review works are reported which explains the application of in situ nasal gel for brain delivery of CNS acting moieties. Hence, in this piece of work, we have initially discussed the global statistics of neurological disorders reported by WHO and other reputed organizations, nasal anatomy, mechanism and challenges of nose-to-brain drug delivery. The work mainly focused on the use of different stimuli-responsive polymers, specifically thermoresponsive, pH-responsive, and ion triggered systems for the development of an effective and controlled dosage form, i.e., in situ nasal gel for brain targeting of bioactives. We have also highlighted the origin, structure, nature and phase transition behavior of the smart polymers found suitable for nasal administration, including poloxamer, chitosan, EHEC, xyloglucan, Carbopol, gellan gum and DGG along with their application in the treatment of neurological disorders. The article is aimed to gather all the information of the past 10 years related to the development and application of stimuli-responsive in situ nasal gel for brain drug delivery., (Copyright © 2020 Elsevier B.V. All rights reserved.)

• Lipid mediated nanostructured lipid carriers, a delivery platform for active plant constituents. • Overcome two potent active plant constituent's solubility/permeability related issues. • Development of Compritol® 888 ATO (solid lipid), and squalene (liquid lipid) based lipid matrix. • Amorphous conversion of active plant constituents after encapsulation inside the lipid matrix. • Safety of NLCs was evidenced through no haemolysis in blood samples. Active plant constituents obtained from edible sources have manifested their pharmacological potential as a therapy against several diseases. But the lack of their desired physicochemical properties such as solubility, permeability ultimately leads to poor bioavailability. Two potent active plant constituents namely, quercetin and piperine having a problem with either solubility or permeability or both, and hence require an advanced lipid-mediated separate formulation system to improve their aforementioned concerns. Concerning advancement in nanoformulations, lipid-based nano-carriers systems have created their mark as a novel drug delivery system. Therefore, an advanced formulation like nanostructured lipid carriers (NLCs) has been formulated individually for both the active plant constituents/drugs through the solvent evaporation technique using high shear homogenization method followed by sonication. Compritol® 888 ATO, a solid lipid, and squalene as liquid lipid was used in their optimized ratios to formulate individual NLCs. Blank and individual drugs loaded NLCs were further characterized for their in vitro physicochemical properties. NLCs showed a negative surface charge with an average particle size below 200 nm. Electron microscopy images showed an anomalous structure of both the formulated NLCs with higher % drug encapsulation efficiency (DEE) with the desired in vitro drug release profile. In the case of quercetin-NLCs, 93.18 ± 5.5 % DEE was observed followed by drug release up to 45.0 ± 1.3 % within 12 h, while piperine-NLCs showed 91.80 ± 2.51 % DEE and drug release up to 38 ± 5.2 % at the same time. XRD and DSC plots showed the conversion of both the drugs into an amorphous structure encapsulated in a lyophilized NLCs matrix. Finally, the safety profile for formulated NLCs was confirmed by haemolysis assay. Hence, the developed active plant constituents enriched NLCs can further be delivered separately and/or in combination, and also may further be evaluated both in vitro and in vivo means. [ABSTRACT FROM AUTHOR]