RESUMEN
Background: Intranasal route offers a direct nose-to-brain delivery via olfactory and trigeminal nerves and minimizes the systemic exposure of the drug. Although reliable and non-invasive, intranasal administration of lipophilic neuroprotective agents for brain targeting is still challenging. Literature focuses on naturally-derived compounds as a promising therapeutics for chronic brain diseases. Naringin, a natural flavonoid obtained from citrus fruits possesses neuroprotective effects. By regulating multiple crucial cellular signaling pathways, naringin acts on several therapeutic targets that make it suitable for the treatment of neurodegenerative diseases like Alzheimer's disease and making it a suitable candidate for nasal administration. However, the hydrophobicity of naringin is the primary challenge to formulate it in an aqueous system for nasal administration. Method: We designed a lipid-based nanoemulsifying drug delivery system of naringin using Acrysol K140 as an oil, Tween 80 as a surfactant and Transcutol HP as a cosolvent, to improve solubility and harness the benefits of nanosizing like improved cellular penetration. Intranasal instillations of therapeutic agents have limited efficacy due to drug washout and inadequate adherence to the nasal mucosa. Therefore, we reconstituted the naringin self-emulsifying system in a smart, biodegradable, ion-triggered in situ gelling hydrogel and optimized for desirable gel characteristics. The naringin-loaded composition was optimized and characterized for various physicochemical and rheological properties. Results: The formulation showed a mean droplet size 152.03 ± 4.6 nm with a polydispersity index <0.23. Ex vivo transmucosal permeation kinetics of the developed formulation through sheep nasal mucosa showed sustained diffusion and enhanced steady-state flux and permeability coefficient. Scanning and transmission electron microscopy revealed the spherical shape of emulsion droplets and entrapment of droplets in a gel structure. The formulation showed excellent biocompatibility as analyzed from the viability of L929 fibroblast cells and nasal mucosa histopathology after treatment. In vivo biodistribution studies revealed significantly higher drug transport and brain targeting efficiency. Conclusion: In situ gelling system with nanoemulsified naringin demonstrated a safe nasal delivery providing a new dimension to the treatment of chronic neurodegenerative diseases using small hydrophobic phytoconstituents with minimization of dose and related systemic adverse effects.
RESUMEN
Drought is a serious abiotic stress, causes worldwide intensive reduction in crop growth and productivity. Plants in contrast to other organisms, do not enjoy the luxury of being able to change their environment or seeking shelters. In this investigation, wheat grains were pre-soaked for 12h in salicylic acid (SA) and/or thiourea (ThU) prior they were left to grow in dry land (40% field water capacity) until harvest. The bio-safety of the harvested wheat was deduced using technical physiological and spectral methods. The pretreatment using SA up to ( approximately 1.5mmol) viewed homologous protein profile and less flag leaf proline in comparison to the non-stressed wheat. In addition, SA-pretreatment has maintained 70% of the emission intensity of yielded grain. The spectra of FTIR were more or less similar in yielded grain and flag leaf in SA-pretreatment. On the other hand, ThU pretreatment induced varied protein profile, higher proline than normal, reduced the fluorescence emission intensity by 52%, and induced varied FTIR spectra. Pretreatment of SA not only has enhanced wheat productivity but also increased yield and straw productions even above the non-treated-non-stressed wheat plant. In contrast to ThU SA was considered safe for drought-stress alleviation in crop plant agriculture.