Several assessment tools were recently introduced for the evaluation of the greenness of analytical methods. Each tool has advantages, disadvantages, and a unique assessment protocol. The final results obtained from each assessment tool may lead to a dissimilar conclusion about the selection of the greenest method, which makes the decision confusing as to which an assessment tool relies on. Accordingly, in this comparative case study, four greenness assessment tools—National Environmental Methods Index (NEMI), Eco-Scale Assessment (ESA), Green Analytical Procedure Index (GAPI), and Analytical GREEnness metric (AGREE)—were tested to evaluate 16 chromatographic methods described in the literature for the assessment of the commonly used antispasmodic drug Hyoscine N-butyl bromide (HNBB). The importance of applying more than one assessment tool when evaluating the greenness of analytical methods is explained in this study. Despite NEMI tool simplicity, it was the least effective in providing information about the analytical method as 14 out of 16 methods had the same NEMI pictogram. ESA and AGREE provided reliable numerical assessments that differed in their total scores whereas the total scores were out of 100 and 1 for each, respectively. AGREE has the merits over ESA with respect to automation and highlighting the weakest points in analytical techniques that need further improvements in terms of greenness. GAPI and AGREE provide fully descriptive three-colored pictograms. The main disadvantage of GAPI is complexity compared to NEMI and ESA. AGREE has the merits of simplicity and automation over GAPI. Based on the results, recommendations are made for ESA, GAPI, and AGREE tools, which provide reliable and precise results about the greenness of the method. Planning for the greenness of analytical methods should be assured before practical trials in a laboratory for reduction of chemical hazards released into the environment. Moreover, inclusion of the evaluation of greenness of analytical methods in method validation protocols is strongly recommended.

This research aimed to design, optimize, and evaluate berberine-laden nanostructured lipid carriers overlaid with chitosan (BER-CTS-NLCs) for efficient brain delivery via the intranasal route. The nanostructured lipid carriers containing berberine (BER-NLCs) were formulated via hot homogenization and ultrasonication strategy and optimized for the influence of a variety of causal variables, including the amount of glycerol monostearate (solid lipid), poloxamer 407 (surfactant) concentration, and oleic acid (liquid lipid) amount, on size of the particles, entrapment, and the total drug release after 24 h. The optimal BER-NLCs formulation was then coated with chitosan. Their diameter, in vitro release, surface charge, morphology, ex vivo permeability, pH, histological, and in vivo (pharmacokinetics and brain uptake) parameters were estimated. BER-CTS-NLCs had a size of 180.9 ± 4.3 nm, sustained-release properties, positive surface charge of 36.8 mV, and augmented ex-vivo permeation via nasal mucosa. The histopathological assessment revealed that the BER-CTS-NLCs system is safe for nasal delivery. Pharmacokinetic and brain accumulation experiments showed that animals treated intranasally with BER-CTS-NLCs had substantially greater drug levels in the brain. The ratios of BER brain/blood levels at 30 min, AUC_brain/AUC_blood, drug transport percentage, and drug targeting efficiency for BER-CTS-NLCs (IN) were higher compared to BER solution (IN), suggesting enhanced brain targeting. The optimized nanoparticulate system is speculated to be a successful approach for boosting the effect of BER in treating CNS diseases, such as Alzheimer’s disease, through intranasal therapy.

The presented study was performed to verify whether rutin and/or quercetin can inhibit liver injury induced by doxorubicin (DXR) in male Wistar rats. In this study, male Wistar rats were treated via the oral route with rutin and quercetin (50 mg/kg) either alone or in combination every other day for five weeks concomitant with receiving intraperitoneal DXR (2 mg/kg) two times a week for five successive weeks. Quercetin, rutin, and their combination significantly improved the deteriorated serum AST, ALT, and ALP activities and total bilirubin level, as well as albumin, AFP, and CA 19.9 levels in DXR‐injected rats. Treatments of the DXR‐injected group with quercetin and rutin prevented the elevation in liver lipid peroxidation and the reduction in superoxide dismutase, glutathione‐S‐transferase and glutathione peroxidase activities, and glutathione content. Treatments with quercetin and rutin significantly repressed the elevated expression of liver p53 and TNF‐α and enhanced Nrf2 expression. Furthermore, the treatments significantly reduced DXR‐induced liver histological changes. In conclusion, rutin and quercetin either alone or in combination may have potential preventive effects against DXR‐induced hepatotoxicity through inhibiting oxidative stress, inflammation, and apoptosis as well as modulating the Nrf2 expression.

This research aimed to boost granisetron (GS) delivery to the brain via the intranasal route to better manage chemotherapy-induced emesis. Glycerol monooleate (GMO), Poloxamer 407 (P 407) and Tween 80 (T 80) were used to formulate GS-loaded cubosomes (GS-CBS) utilizing a melt dispersion-emulsification technique. GS-CBS were characterized by testing particle diameter, surface charge and entrapment efficiency. The formulations were optimized using a Box–Behnken statistical design, and the optimum formula (including GMO with a concentration of 4.9%, P 407 with a concentration of 10%, and T 80 with a concentration of 1%) was investigated for morphology, release behavior, ex vivo permeation through the nasal mucosa, and physical stability. Moreover, the optimal formula was incorporated into a thermosensitive gel and subjected to histopathological and in vivo biodistribution experiments. It demonstrated sustained release characteristics, increased ex vivo permeability and improved physical stability. Moreover, the cubosomal in situ gel was safe and biocompatible when applied to the nasal mucosa. Furthermore, compared to a drug solution, the nose-to-brain pathway enhanced bioavailability and brain distribution. Finally, the cubosomal in situ gel may be a potential nanocarrier for GS delivery to the brain through nose-to-brain pathway.