SAID SHEHATA

The transition from Green to sustainable chemistry demands a paradigm shift in how analytical methodologies are evaluated, moving beyond isolated performance metrics toward holistic life-cycle assessment. In this study, we introduce a novel Sustainability Assessment Framework (Greenness, Applicability, Sustainability) to rigorously benchmark analytical strategies. As a proof-of-concept, the framework was applied to a complex pharmaceutical challenge: the impurity profiling of paracetamol (PAR) along with three official impurities: para-aminophenol (PAP), para-nitrophenol (PNP), and para-chloroacetanilide (PCA), and two co-formulated drugs ibuprofen (IBU) and chlorzoxazone (CHZ). Two chemometric models, partial least squares (PLS) and artificial neural networks (ANN), were utilized to achieve this purpose. Furthermore, both models were subjected to a variable selection process using genetic algorithm (GA) to identify the most significant wavelengths. The genetic algorithm-optimized neural network (GA-ANN) demonstrated superior predictive accuracy for the six-component mixture. The core innovation of this work lies in the comparative application of the Sustainability Assessment Framework, benchmarking the proposed chemometric method against a reference HPLC method using eight state-of-the-art metrics. Greenness was evaluated via Analytical Eco-Scale, GAPI, and AGREE; Applicability via BAGI, RGB12 algorithm, and EPPI; and Sustainability via the Carbon Footprint, NQS Index, and %Circularity. This study establishes the Framework as a robust prototype for modern quality control, validating chemometrics not merely as an alternative technique, but as a superior sustainable evolution aligned with the principles of the circular economy.

The COVID-19 pandemic has emphasized the critical need for novel therapeutic approaches. Favipiravir (FAV), an antiviral drug primarily used for influenza, has shown promising potential in treating COVID-19 and other RNA viral infections. A precise, reliable, and rapid fluorimetric method was established for the quantification of FAV in pharmaceutical formulations, even in the presence of its acid-induced degradation product. The acid-induced degradation product (ADP) of FAV was prepared through forced degradation, followed by characterization using IR and MS. The method leveraged the intrinsic fluorescence characteristics of FAV, exhibiting a linear response within the concentration range of 5–80 ng/mL at 416.5 nm using the first-order derivative processing. Key methodological parameters were optimized to enhance sensitivity, achieving detection and quantification limits of 1.6 ng/mL and 4.8 ng/mL, respectively. All calibration and fluorimetric measurement steps were performed in distilled water without the use of organic solvents or buffers, making the analytical determination phase entirely aqueous and environmentally benign. This method was effectively applied to FAV in both pure drug and pharmaceutical dosage forms. Compared with previously reported fluorimetric methods, it offers the unique combination of aqueous-based operation, stability-indicating capability, and superior analytical performance. Additionally, its environmental sustainability was evaluated using GAPI, AGREE, and RGB12 metrics, which confirmed its green and eco-friendly attributes.

Eukaryotic elongation factor 2 kinase (eEF2K) phosphorylates eukaryotic elongation factor 2 (eEF2) and slows translation elongation. In the nervous system, this pathway links neuronal activity, calcium signaling, energy status, and stress responses to selective protein synthesis programs that shape synaptic plasticity, circuit excitability, and cell survival. Dysregulated eEF2K/eEF2 signaling has been implicated in epilepsy, Alzheimer's disease, Parkinson's disease, major depressive disorder, Down syndrome, and other brain conditions. However, the literature remains fragmented, largely preclinical, and often interpreted in an overly therapeutic manner. This review synthesizes the field using a mechanistic framework. Across disorders, altered eEF2 phosphorylation converges on five major axes: synaptic plasticity and excitatory/inhibitory balance, oxidative and mitochondrial stress responses, neuroinflammation/neuroimmune regulation, and aging-related neurogenesis and cognitive resilience. In chronic neurodegenerative and neurodevelopmental settings, excessive eEF2K activity is frequently associated with impaired de novo protein synthesis, synaptic dysfunction, and cognitive decline, whereas genetic or pharmacological suppression can improve selected behavioral and electrophysiological outcomes. By contrast, in acute metabolic stress or certain immune-cell contexts, eEF2K activity may serve adaptive and anti-inflammatory functions. These findings indicate that eEF2K has context-dependent, rather than uniformly pathogenic, roles. We also highlight major translational barriers, including dependence on rodent models, limited causal human data, incomplete cell-type resolution, and the off-target liabilities of commonly used inhibitors such as NH125 and A-484954. Overall, the eEF2K/eEF2 axis represents a biologically important but therapeutically complex target that will require selective, cell-aware, and stage-specific modulation. Future progress depends on better biomarkers, human models, and more selective brain-penetrant inhibitors.

Despite advances, detailed insight into cancer's biological mechanisms remains needed. Isatin, an indole-1 H-2,3-dione, is an attractive agent for new drug discovery. Here, the anticancer efficacy and potential toxicity of isatin in combination with doxorubicin (Dox) in a mouse Ehrlich solid carcinoma (ESC) model were examined by modulating the PI3K/AKT/EMT pathway. Five groups of fifty female mice were prepared: negative control, positive ESC-bearing mice, isatin-treated ESC group, Dox-treated ESC group, and isatin and Dox combination-treated ESC group. Treatments began after tumor formation. Inflammatory markers, kidney and liver enzyme activities, and EMT markers levels (vimentin and E-cadherin) were assessed by ELISA. HIF 1 α, NF-κB, PI3K, AKT, MMP2, and MMP9 gene expression was evaluated using qRT-PCR. Protein expression of MMP-9 and E-cadherin was assessed by IHC. Compared with the positive control, the combined treatment reduced tumor growth by 51%. Additionally, combined treatment showed a significant increase in the amount of necrotic tissue. Mechanistically, isatin exerted its therapeutic effect by increasing anti-inflammatory (IL-10) cytokine levels and suppressing pro-inflammatory (IL-6) cytokine levels, along with reductions in HIF-1α, NF-κB, PI3K, AKT, MMP2, and MMP9 mRNA levels. Also, a combined group of isatin and Dox showed reduced vimentin levels and elevated E-cadherin levels by ELISA. Co-administration of isatin and Dox significantly increased E-cadherin expression and attenuated MMP-9 expression compared with the untreated group, as assessed by IHC. Our results indicate that isatin, in combination with doxorubicin, exerts a synergistic anticancer effect against ESC, offering a promising therapeutic approach to enhance treatment efficacy.

OBJECTIVES: The study investigated thyroid function, oxidative stress and PI3K/AKT/FoxO3 pathway in employees occupationally exposed to a noise.

METHODS: Environmental noise levels were measured along with assessment of Serum levels of T3, T4, TSH, MDA, and TAC and gene expression of NOXO3, PI3K, AKT, and FoxO3.

RESULTS: The mean noise level was 90.50 ± 4.43 dB. The serum levels of MDA and TSH were statistically higher, while TAC, T3, and T4 were lower among noise-exposed workers. PI3K and AKT were downregulated in noise-exposed workers, whereas FoxO3 and NOXO3 were upregulated, with a significant correlation between them.

CONCLUSIONS: The noise-exposed workers had thyroid dysfunction issues linked to high oxidative stress. Downregulation of PI3K and AKT and upregulation of FoxO3 might reflect a cellular defense against oxidative stress. Collectively, noise should be considered as a systemic health risk.

Multiple sclerosis (MS) is a chronic, immune-mediated demyelinating disorder of the central nervous system characterized by inflammation and progressive neurodegeneration. MS is a heterogeneous disease with varying presentations, disease courses, and prognosis. Although current disease-modifying therapies (DMTs) have been reported to reduce the frequency and severity of inflammatory demyelinating hallmarks of MS, improve relapse rate and long-term outcomes, they do not fully prevent disease progression, nor do they reverse existing neurological damage. This ongoing gap has driven growing interest in natural products as complementary or adjunctive strategies for MS management. Naturally occurring phytochemicals have been proposed as a potentially safe and effective therapeutic and complementary option for MS. Natural compounds have been reported to demonstrate anti-inflammatory, immunomodulatory, antioxidant, and neuroprotective activities in experimental models of MS. Together, these multifunctional properties target key mechanistic pathways implicated in disease pathogenesis, such as oxidative stress, mitochondrial dysfunction, and immune dysregulation. However, despite promising preclinical data, clinical translation remains limited by variability in dosing, bioavailability challenges, and insufficient large-scale trials. In this context, this review explores the scientific rationale for natural products in MS, provides an overview of disease mechanisms relevant to such interventions, and highlights future research needs to advance these compounds toward evidence-based integration.

The multi-label retinal disease classification is a difficult one since fundus images might comprise many co-occurring abnormalities, extreme in relation to the class, as well as significant lesion appearance variation. In order to deal with this issue, this paper suggests a combined deep learning architecture to diagnose retinal diseases automatically with the help of the MuReD dataset, which includes 2208 fundus images that were gathered at ARIA, STARE, and RFMiD and reformulated with 19 retinal disease labels, excluding the non-diagnostic category of OTHERS. The proposed model is based on a hybrid convolutional structure that integrates two complementary branches of feature extraction and implements a multi-stage preprocessing pipeline consisting of contrast enhancement, luminance correction, noise reduction, and retinal masking. Fusion and optimization of extracted feature representations are performed to perform multi-label prediction with binary supervision of label-wise predictions as sigmoid outputs. In order to assess the value of architecture and preprocessing design, ablation experiments were performed on a great scale by using single-backbone baselines, hybrid configurations, and preprocessing-specific configurations. According to the results, the highest F1-micro = 0.5484, PR-AUC micro = 0.5696, and ROC-AUC micro = 0.9349 were observed in the best variant of the hybrid, and the best PR-AUC micro = 0.5821 and ROC-AUC micro = 0.9369 were observed in another hybrid variant. Other tests on bootstrap confidence interval, calibration evaluation, Monte Carlo dropout, and repeated multi-seed experiments also indicated the strength of the proposed model. These results reveal that feature fusion with built-in deep learning is an effective solution to multi-label retinal disease diagnosis and has a potential real-world application to computer-aided screening and triage in ophthalmology.

Mitochondrial dynamics disruption and the proapoptotic proteins activation are reported to be the major protagonists of the pathological alterations in cisplatin-induced nephrotoxicity. This study assessed the impact of modulating Sig-1R activity by fabomotizole and/or sertraline on cisplatin nephrotoxicity focusing on the regulation of renal mitochondrial homeostasis and apoptotic cellular death. Four groups of rats received a single cisplatin injection, and were assigned to: cisplatin control, sertraline-treated, fabomotizole-treated, sertraline + fabomotizole-treated groups, along with a fifth normal control group. In parallel, HEK293 cells were used to evaluate the effects of the tested agents on renal cell viability. Elevated concentrations of sertraline reduced HEK293 cell viability. Additionally, sertraline maintained the noxious effect of cisplatin on mitochondrial homeostasis and renal apoptosis in rats. In contrast, fabomotizole improved cell viability in HEK293 cells exposed to cisplatin. It preserved the structural integrity of the renal tubular cells and suppressed plasma levels of NGAL, BUN and creatinine in cisplatin-intoxicated rats. Electron microscopy revealed that fabomotizole restored mitochondrial homeostasis, as shown by increased mitochondrial density. Mechanistically, fabomotizole downregulated the mitochondrial fission mediator Drp1 while upregulating the mitochondrial fusion mediator Mfn1; this was reflected on the mitochondrial function by reinstating renal ATP content. Furthermore, fabomotizole hindered ERK1/2 activation and reduced the proapoptotic proteins, Bax and Bak along with caspase 3 activity. As demonstrated by the Sig-1R antagonistic effect of sertraline, which notably negated fabomotizole's renoprotective potential, fabomotizole's capacity to preserve stable mitochondrial dynamics and hamper apoptosis following cisplatin nephrotoxicity may be ascribed to its Sig-1R activation-mediated ERK 1/2 inhibition.

Metal fabrication workers are susceptible to various work-related musculoskeletal disorders (WMSDs) due to their awkward posture. This study aimed to identify the association between ergonomic posture risk and the frequency of musculoskeletal disorders (MSDs). . The cross-sectional study was conducted in metal fabrication workshops, including 132 workers. The Nordic musculoskeletal questionnaire (NMQ) was used to determine the prevalence of WMSDs, and posture assessment techniques (rapid upper limb assessment [RULA]) were applied to evaluate the ergonomic risk. . The NMQ revealed that 79.5% of participants had experienced pain/discomfort in the past year and 44.7% reported pain/discomfort in the previous 7 days. Musculoskeletal problems were most prevalent in the neck, shoulder and lower back joints (53, 40.9 and 50%, respectively). All individuals fell into RULA risk categories of moderate and high risk. Among the workers, 68.2% had high risk (RULA scores of >6) while 31.8% had medium risk (RULA scores of 5-6). A significant correlation was found between pain/discomfort in the neck and lower back joints and high RULA risk. . This study found that, among metal fabrication workers, higher RULA scores were associated with a higher prevalence of MSDs, emphasizing the importance of ergonomic interventions focused on high-risk positions.

Baicalin, a polyphenolic flavonoid, is the main bioactive flavone extracted from the roots of Scutellaria baicalensis. It has received increasing interest due to its broad spectrum of pharmacological activities and therapeutic benefits demonstrated in preclinical research. However, its molecular mechanisms and translational potential remain underdefined. This review systematically evaluates current evidence on baicalin, including its natural sources, chemical structure, biosynthesis, extraction techniques, pharmacokinetic features, molecular mechanisms, and therapeutic applications, as well as developments in drug delivery platforms designed to overcome its biopharmaceutical limitations. This structured literature review was conducted using data extracted from various databases, including the Egyptian Knowledge Bank, Scopus, Web of Science, PubMed, Google Scholar, and Elsevier. All possible keywords relevant to baicalin were utilized. Recent original articles, systematic reviews, meta-analysis, clinical studies, and high-quality reviews were prioritized. Baicalin exerts its therapeutic effects through modulation of various signaling pathways, primarily involving oxidative stress and inflammation. It exhibits anticancer, antimicrobial, antiviral, immunomodulatory, metabolic, and dermatological effects and alleviates various system disorders and drug-induced toxicity. Despite promising preclinical data, clinical translation is hindered by its poor solubility, limited bioavailability, and insufficient clinical validation. Emerging nano-delivery systems, such as liposomes, solid lipid nanoparticles, polymeric nanoparticles, and surface-modified nanoplatforms, have greatly improved the pharmacokinetic performance of baicalin. Nevertheless, the clinical translation of these approaches remains limited. While baicalin represents a promising multi-target therapeutic option, substantial research gaps remain. Future research should give priority to deeper mechanistic investigations, standardized formulation approaches, and well-designed clinical trials to bridge the gap between preclinical efficacy and clinical application, and to establish its optimal dosing, safety profile, and long-term efficacy.

Purinergic P2X receptor overactivation, impaired mitophagy, and NLRP3 inflammasome-driven neuroinflammation have been increasingly implicated in Parkinson's disease (PD) pathogenesis. Suramin, a purinergic receptor antagonist, has recently attracted attention for its neuroprotective effects in several neurological disorders. However, its potential to modulate the P2X/mitophagy/NLRP3 axis in PD remains unexplored. This study evaluated the neuroprotective effects of suramin in comparison with metformin, a reported mitophagy and inflammasome modulator, in a rotenone-induced PD rat model. Rotenone (1.5 mg/kg, s.c.) was administered on alternate days for three weeks. Suramin (100 mg/kg, I.V.) was administered on days 11 and 18, while metformin (200 mg/kg, p.o.) was given from days 11 to 21. Behavioral outcomes were evaluated using the open-field, footprint, grip strength, and rotarod tests. Expression levels of selected target signals were quantified using qPCR, ELISA, Western blot, and immunohistochemistry. Suramin and metformin significantly improved motor and behavioral performance, preserved dopaminergic integrity, improved tyrosine hydroxylase expression, and diminished α-synuclein accumulation, with suramin demonstrating greater efficacy. At the molecular level, suramin more effectively downregulated striatal P2X7R, P2X4R, and ROS levels and increased p-AMPK/t-AMPK ratio. Both treatments promoted mitophagy, as evidenced by increased PINK1, Parkin, and BNIP3 levels along with reduced LC3-II/I ratio. They also suppressed NLRP3 inflammasome activation and pyroptosis, with suramin showing more potent anti-inflammatory effects. Altogether, suramin's neuroprotective effects could be mediated via suppressing P2X7/P2X4 receptors, enhancing mitophagy and counteracting NLRP3-driven pyroptosis in the striatum, with its relatively stronger profile attributable to more robust P2X7/P2X4 signaling inhibition, underscoring its potential as a therapeutic candidate for PD.

Egypt's landmark success in eliminating HCV and controlling HBV proves that large-scale, coordinated public health strategies can yield transformative results. However, the rising burden of MASLD now threatens these achievements. Confronting this emerging epidemic with the same urgency, innovation, and scale will be critical to safeguarding the gains of the past decade and securing the future of global liver health.

Cariprazine, a third-generation antipsychotic, is indicated for schizophrenia and bipolar I disorder. Affordable formulations are essential for improving access and adherence, particularly in resource-limited settings. We aimed to assess the bioequivalence, safety, and tolerability of a newly developed generic hard capsule Vocarzine (1.5 mg) compared to a branded reference product of cariprazine hard capsule (Reagila®) under fasting conditions in healthy adult participants. In a randomized, open-label, single-dose, two-period, two-sequence crossover design, 30 healthy male and female participants received a single oral dose of either the test or reference product, with 4-week washout period. Pharmacokinetics were evaluated using validated LC-MS/MS methods. Bioequivalence was concluded if the 90% confidence intervals (CIs) for the geometric mean ratios (GMRs) of peak plasma concentration (C) and area under the concentration-time curve from time zero to 72 h (AUC) fell within 80-125%. Twenty-nine participants completed the study. The GMR (90% CI) for C was 91.92% (85.07-99.33%) and for AUC was 92.85% (88.86-97.02%), both within the bioequivalence acceptance range (80-125%). Both formulations were well tolerated; mild nausea was the most common adverse event, and no serious adverse events were reported. The two hard capsule formulations were bioequivalent, in terms of rate and extent of absorption, with a comparable safety profile, supporting the use of vocarzine as a safe, effective, and potentially cost-saving alternative. Clinical trial number: The ClinicalTrials.gov registration number is NCT07121868, retrospectively registered on August 13, 2025.

OBJECTIVES: To evaluate the effect of a novel restorative approach using dimethyl sulfoxide (DMSO) as a cavity pretreatment on the material fracture and retention (primary outcome) of direct composite fillings placed on cervical carious lesions (CCLs).

METHODS: 45 patients presenting CCLs were screened and randomized into two groups containing 37 caries lesions/group: an untreated control (20 patients) and a DMSO-treated (25 patients) group. Following a parallel-study design, two calibrated operators placed 74 (n = 37) composite fillings (Filtek Z350XT, 3 M ESPE) using a 2-step etch-and-rinse adhesive (Single Bond 2, 3 M ESPE). After baseline assessments (7 days), fillings were evaluated at 12-, 24- and 36-month follow-ups according to the FDI criteria (fracture/retention, marginal staining, marginal adaptation, postoperative sensitivity and caries recurrence). For statistical analysis, Chi-Square and Cochran's Q tests were used (α = 0.05) following the Bonferroni correction.

RESULTS: DMSO had significant effects on the clinical performance of composite fillings placed on CCLs according to the FDI criteria (p < 0.05). Success rates after 36 months of untreated and DMSO-treated cavities were 65 % and 89 %, respectively, with a 70 % lower risk of failure when using DMSO. DMSO significantly reduced post-operative sensitivity and marginal staining and improved retention rates after 36 months (p < 0.05).

CONCLUSIONS: Long-term clinical performance of composite fillings using simplified etch-and-rinse adhesives can be optimized by employing DMSO as a cavity pretreatment.

CLINICAL SIGNIFICANCE: The use of DMSO can be a simple clinical approach to improve post-operative sensitivity of composite fillings, reduce risk of failures and extend service life by producing more stable composite-tooth interfaces.

OBJECTIVES: To evaluate the effect of a novel restorative approach using dimethyl sulfoxide (DMSO) as a cavity pretreatment on the material fracture and retention (primary outcome) of direct composite fillings placed on cervical carious lesions (CCLs).

METHODS: 45 patients presenting CCLs were screened and randomized into two groups containing 37 caries lesions/group: an untreated control (20 patients) and a DMSO-treated (25 patients) group. Following a parallel-study design, two calibrated operators placed 74 (n = 37) composite fillings (Filtek Z350XT, 3 M ESPE) using a 2-step etch-and-rinse adhesive (Single Bond 2, 3 M ESPE). After baseline assessments (7 days), fillings were evaluated at 12-, 24- and 36-month follow-ups according to the FDI criteria (fracture/retention, marginal staining, marginal adaptation, postoperative sensitivity and caries recurrence). For statistical analysis, Chi-Square and Cochran's Q tests were used (α = 0.05) following the Bonferroni correction.

RESULTS: DMSO had significant effects on the clinical performance of composite fillings placed on CCLs according to the FDI criteria (p < 0.05). Success rates after 36 months of untreated and DMSO-treated cavities were 65 % and 89 %, respectively, with a 70 % lower risk of failure when using DMSO. DMSO significantly reduced post-operative sensitivity and marginal staining and improved retention rates after 36 months (p < 0.05).

CONCLUSIONS: Long-term clinical performance of composite fillings using simplified etch-and-rinse adhesives can be optimized by employing DMSO as a cavity pretreatment.

CLINICAL SIGNIFICANCE: The use of DMSO can be a simple clinical approach to improve post-operative sensitivity of composite fillings, reduce risk of failures and extend service life by producing more stable composite-tooth interfaces.

The loss of intracellular K facilitated by different channels such as Panx1, TWIK2, or Kv1.3, is a danger signal that activates programmed cell death in oligodendrocytes via NLRP3 inflammasome and pyroptosis in multiple sclerosis (MS). ATP triggers P2X7 purinergic receptors, which coordinate TWIK-2 and Panx-1 channels. Given this hierarchical signaling architecture, the present study postulated that strategic Kv1.3 intervention using Dalfampridine (Dal) could mirror comprehensive P2X7 blockade with Suramin (Sur) in the experimental autoimmune encephalomyelitis (EAE) as MS animal model. EAE mice received either Dal (10 µg/mouse/day, oral for 2 weeks) or a single Sur injection (100 mg/kg, intraperitoneal). Both interventions demonstrated comparable efficacy in restoring motor function in open field and rotarod tests, preserving myelin integrity under Luxol fast blue stain, and attenuating neuroinflammatory infiltrates within spinal tissues. Molecular profiling confirmed EAE-associated hyperactivation of the ATP-P2X7R-K⁺ efflux cascade. Sur exerted broad-spectrum inhibition, suppressing ATP accumulation, P2X7R overexpression, and all three channels. Conversely, Dal specifically reduced Kv1.3 expression while leaving ATP levels, P2X7R, TWIK-2, and pannexin-1 unchanged. Remarkably, both compounds achieved equivalent disruption of NEK7/Ripk1/FADD/NLRP3 inflammasome complex and pyroptotic machinery, including pro-caspas1 activation and subsequent gasdermin-D cleavage. These findings suggest that Kv1.3 may serve as a contributory node where downstream channel modulation can deliver neuroprotection equivalent to the upstream pathway intervention. By modulating this potential checkpoint, Kv1.3-targeted therapy may reduce collateral effects associated with pan-purinergic blockade, offering a potential streamlined therapeutic corridor for demyelinating neuroinflammation with enhanced specificity and reduced systemic burden.

This research focuses on creating a novel Brijaluronic-based terpesomal system capable of transporting quercetin (QER) efficiently to the brain. The vesicles were fabricated through an ethanol-injection method and then refined using a structured optimization approach in Design-Expert® software. The influence of three main formulation parameters: terpene-to-drug ratio, surfactant type, and hyaluronic acid amount were evaluated. The optimization process was designed to maximize EE%, minimize VS, and maintain ZP within an acceptable stability range. The optimal formula hit a desirability target of 0.957. It achieved an 88.66% EE%, featured nano-carriers sized at 72.09 nm, and had a stable charge of - 26.5 mV. Physicochemical characterization studies revealed a spherical morphology, an in-vitro release defined by a biphasic profile, and a secure structural integrity which was validated using FTIR analysis. Moreover, over the course of three months, the formulation did not degrade or change significantly, demonstrating its high degree of stability. Notably, terpesomes demonstrated a ~ 3.5-fold enhancement in antioxidant activity, reducing the IC₅₀ from 12.98 ± 0.82 µg/mL to 3.68 ± 0.20 µg/mL, representing a statistically and pharmacologically significant improvement. Radio-kinetic assessments further supported its potential for precise brain targeting. The brain/blood was highest for the optimized formulation at all-time points. Compared with the nasal QER solution, Technetium-99m ([Tc]Tc)-QER-loaded terpesomes exhibited superior brain-targeting efficiency, as evidenced by higher AUC, shorter T, and greater C values in the brain. Taken together, the Brijaluronic terpesomes represent a highly promising, innovative nano-platform. This engineered system appears poised to boost the effectiveness of QER in neurotherapeutic applications.