Rosemary oil low energy nanoemulsion: optimization, µrheology, in silico, in vitro, and ex vivo characterization.

Acetylcholine imbalance in the human brain causes dementia-related symptoms of Alzheimer's disease. Acetylcholinesterase (AChE) inhibitors prevent the lysis of acetylcholine in the brain and prevent dementia. Therefore, the present study aims to investigate the in silico and in vitro AChE potential of rosemary oil and then formulate it into nanoemulsion as an adjuvant with co-administration of Donepezil (Dz) with a thought for futuristic target for Alzheimer's diseases via the intranasal route. The aim for preparing this formulation was to add the AChE inhibition effect of the rosemary oil to the effect that acts as an additive effect along with Dz. The docking score of rosemary oil components on human cholinesterase 1GQR protein was found to be >-5 kcal/mol. In vitro AChE activity of rosemary oil confirms the prominent IC50 of oil at 0.001 µL/min. Nanoemulsion was prepared by low energy emulsification technique using Tween 80 as surfactant and ethanol or diethylene glycol monoethyl ether as cosurfactant. Droplet size, polydisperity index, and zeta potential of stable nanoemulsion was ∼16 nm, 0.1, and -6.05 mV for stable batch. High-resolution transmission electron microscopy microscopic studies depicted the spherical shape of the droplet. Micro rheology investigation of nanoemulsion clearly attributes to gel-sol-gel behaviour of formulated nanoemulsion. Thermal evaluation of nanoemulsion depicts the phase transition behaviour of ethanol-based nanoemulsion at 60 °C. Ex vivo nasal ciliotoxicity and permeation studies of formulation establish the safety of ethanol-based rosemary oil-loaded nanoemulsion and permeation mechanism of Dz from the nanoemulsion. In vitro permeation studies showed more drug penetration from the nanoemulsion as compared to the plain drug. The prepared nanoemulsion was found to be stable for 3 months at 4, 25, and 45 °C of storage. This low energy preparation method can be advantageous for the preparation of scalable nanoemulsion and can be a futuristic therapeutic for Alzheimer's disease.

Recent advances in lipid-engineered multifunctional nanophytomedicines for cancer targeting.

Cancer is a leading cause of death in many countries around the world. However, the efficacy of current treatments available for variety of cancers is considered to be suboptimal due to the pathophysiological challenges associated with the disease which limits the efficacy of the anticancer drugs. Moreover, the vulnerability towards off-target effects and high toxicity also limits the use of drugs for the treatment of cancers. Besides, the biopharmaceutical challenges like poor water solubility and permeability of the drugs, along with the absence of active targeting capability further decreases the utility of drugs in cancer therapy. As a result of these deficiencies, the current therapeutic strategies face noncompliance to patients for providing meaningful benefits after administration. With the advancements in nanotechnology, there has been a paradigm shift in the modalities for cancer treatment with the help of phytomedicine-based nanosized drug delivery systems coupled with variegated surface-engineering strategies for targeted drug delivery. Among these delivery systems, lipid-based nanoparticles are considered as one of the highly biocompatible, efficient and effective systems extensively explored for anticancer drug delivery. These include diverse range of systems including liposomes, nanoemulsions, solid lipid nanoparticles, nanostructured lipidic carriers and supramolecular carriers, which alters pharmacokinetic and biodistribution of the drugs for active targeting to the desired site of action by overcoming the biopharmaceutical challenges associated with anticancer drug delivery. The present review endeavours to provide a comprehensive account on the recent advances in the application of lipid-based nanostructured systems for improving the pharmacotherapeutic performance of phytomedicines for cancer targeting application.

Therapeutic potential of nanoemulsions as feasible wagons for targeting Alzheimer's disease.

Alzheimer's disease (AD) is an irreversible dementia state with characteristic clinical manifestations, including declining cognitive skills and loss of memory, which particularly affects the older population. Despite significant efforts in the field of nano-based drug delivery, there have been few successes achieved in the design of a rational drug therapy. Nanoemulsions (NEs) have potential for the delivery of AD therapeutics owing to their capability for brain drug delivery. Still, there is a long way to go before such therapeutics become a reality in the clinic. In this review, we highlight the preclinical assessment of NEs for AD and discuss the regulatory constraints to their clinical acceptance.