Fluorescein Based Fluorescence Sensors for the Selective Sensing of Various Analytes.

Fluorescein molecules are extensively used to develop fluorescent probes for various analytes due to their excellent photophysical properties and the spirocyclic structure. The main structural modification of fluorescein occurs at the carboxyl group where different groups can be easily introduced to produce the spirolactam structure which is non-fluorescent. The spirolactam ring opening accounts for the fluorescence and the dual sensing of analytes using fluorescent sensors is still a topic of high interest. There is an increase in the number of dual sensors developed in the past five years and quite a good number of fluorescein derivatives were also reported based on reversible mechanisms. This review analyses environmentally and biologically important cations such as Cu2+, Hg2+, Fe3+, Pd2+, Zn2+, Cd2+, and Mg2+; anions (F-, OCl-) and small molecules (thiols, CO and H2S). Structural modifications, binding mechanisms, different strategies and a comparative study for selected cations, anions and molecules are outlined in the article.

Enhancement in brain uptake of vitamin D3 nanoemulsion for treatment of cerebral ischemia: formulation, gamma scintigraphy and efficacy study in transient middle cerebral artery occlusion rat models.

AIM: For the treatment of cerebral ischaemia, vitamin-D3 loaded nanoemulsions were developed. METHOD: Tween 20 and polyethylene glycol were chosen as surfactant/co-surfactant, while oleic acid as the oil phase. The formulation was characterised for various in-vitro parameters. Targeting efficiency was investigated through radiometry, gamma scintigraphy and efficacy was studied in transient middle cerebral artery occlusion (MCAo) rat model. RESULT: Vitamin D3-nanoemulsion showed a mean size range of 49.29 ± 10.28 nm with polydispersity index 0.17 ± 0.04 and zeta potential 13.77 mV. The formulation was found stable during thermodynamic stability study and permeated within 180 min through sheep nasal mucosa (permeation coefficient 7.873 ± 0.884 cm/h). Gamma scintigraphy and radiometry assay confirmed better percentage deposition (2.53 ± 0.17%) of 99mTc-vitamin D3-nanoemulsion through nasal route compared to IV administered 99mTc-vitamin D3 solution (0.79 ± 0.03%). Magnetic Resonance Imaging (MRI) of the ischaemic model confirmed better efficacy of vitamin D3-nanoemulsion. CONCLUSION: This work demonstrated better permeation, deposition, and efficacy of vitaminD3-nanoemulsion through the intranasal route.

Skin emitted volatiles analysis for noninvasive diagnosis: the current advances in sample preparation techniques for biomedical application.

Human skin emits a series of volatile compounds from the skin due to various metabolic processes, microbial activity, and several external factors. Changes in the concentration of skin volatile metabolites indicate many diseases, including diabetes, cancer, and infectious diseases. Researchers focused on skin-emitted compounds to gain insight into the pathophysiology of various diseases. In the case of skin volatolomics research, it is noteworthy that sample preparation, sampling protocol, analytical techniques, and comprehensive validation are important for the successful integration of skin metabolic profiles into regular clinical settings. Solid-phase microextraction techniques and polymer-based active sorbent traps were developed to capture the skin-emitted volatile compounds. The primary advantage of these sample preparation techniques is the ability to efficiently and targetedly capture skin metabolites, thus improving the detection of the biomarkers associated with various diseases. In further research, polydimethyl-based patches were utilized for skin research due to their biocompatibility and thermal stability properties. The microextraction sampling tools coupled with high sensitive Gas Chromatography-Mass Spectrometer provided a potential platform for skin volatolomes, thus emerging as a state-of-the-art analytical technique. Later, technological advancements, including the design of wearable sensors, have enriched skin-based research as it can integrate the information from skin-emitted volatile profiles into a portable platform. However, individual-specific hydration, temperature, and skin conditions can influence variations in skin volatile concentration. Considering the subject-specific skin depth, sampling time standardization, and suitable techniques may improve the skin sampling techniques for the potential discovery of various skin-based marker compounds associated with diseases. Here, we have summarised the current research progress, limitations, and technological advances in skin-based sample preparation techniques for disease diagnosis, monitoring, and personalized healthcare applications.

Fusogenic liposome-coated nanoparticles for rapid internalization into donor corneal endothelial tissue to enable prophylaxis before transplantation.

Cold stress (hypothermia) during storage and cytokine stress due to acute allograft rejection adversely affect the donor corneal endothelium in the short term. Pharmacological pre-treatment (before transplantation) of the donor corneal endothelium or cells (propagated in vitro for cell injection therapy) with microtubule stabilizers, cold stress protectants, and other molecules is an attractive strategy to tackle damage caused by hypothermia and cytokine stress. These molecules can be delivered intracellularly to the donor corneal endothelium or cells at controlled rates for desired periods and with one-time administration using nanoparticles. However, the death-to-preservation time of donor corneas of more than 4 to 6 h significantly decreases endothelial cell density and increases the risk of microbial contamination. Therefore, we have developed fusogenic liposome-coated nanoparticles for rapid internalization of nanoparticles into cultured corneal endothelial cells and ex vivo corneal endothelial tissue. Here, we have shown that the fusogenic liposome-coated nanoparticles have the intrinsic ability to efficiently and rapidly internalize into cultured corneal endothelial cells and ex vivo corneal tissue within 3 h by possibly fusing with the cell membrane and bypassing the endocytic pathway. Lactate dehydrogenase assay showed that the internalized fusogenic liposome-coated nanoparticles did not cause cytotoxicity in endothelial cells associated with the ex vivo cornea for at least up to 2 days. Thus, fusogenic liposome-coated nanoparticles have great potential as a platform for engineering cells and endothelial tissue of donor corneas to facilitate prophylactic drug delivery during storage and after transplantation.

Alpha-Lipoic Acid Protects Co-Exposure to Lead and Zinc Oxide Nanoparticles Induced Neuro, Immuno and Male Reproductive Toxicity in Rats.

We evaluated the neuro-, immuno-, and male reproductive toxicity of zinc oxide nanoparticles (ZnO NPs) alone and in combination with lead acetate. We also studied the therapeutic role of α-lipoic acid postexposure. Lead (10 mg/kg, body weight), ZnO NPs (100 mg/kg, bwt) alone, and their combination were administered orally in Wistar rats for 28 days, followed by the administration of α-lipoic acid (15 mg/kg, bwt) for the next 15 days. Our results demonstrated protective effects of α-lipoic acid on lead and ZnO NP-induced biochemical alterations in neurological, immunological, and male reproductive organs in rats. The altered levels of blood δ-aminolevulinic acid dehydratase (ALAD), immunoglobulins (IgA, IgG, IgM, and IgE), interleukins (IL-1ß, IL-4, and IL-6), caspase-3, and tumor necrosis factor (TNF-α) were attenuated by lipoic acid treatment. Lead and ZnO NP-induced oxidative stress was decreased by lipoic acid treatment, while a moderate recovery in the normal histoarchitecture of the brain section (cortex and hippocampus) and testes further confirmed the neuro- and male reproductive toxicity of lead and ZnO NPs. We also observed a significant decrease in the blood metal content in the animals treated with lipoic acid compared to the lead-administered group, indicating the moderate chelating property of lipoic acid. It may thus be concluded that lipoic acid might be a promising protective agent against lead and ZnO NP-induced alterations in the neurological, immunological, and reproductive parameters.