The 2023 iteration of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) estimated prevalence, incidence, and health burden for 375 diseases and injuries, including 12 mental disorders. We assess past, current, and emerging trends in the prevalence and burden of mental disorders across sexes and age groups, for 21 regions, 204 countries and territories, and by Socio-demographic Index (SDI) quintile, from 1990 to 2023. Mental disorders included in GBD 2023 were anxiety disorders, major depressive disorder, dysthymia, bipolar disorder, schizophrenia, autism spectrum disorders, conduct disorder, attention-deficit hyperactivity disorder, anorexia nervosa, bulimia nervosa, idiopathic developmental intellectual disability, and a residual category of other mental disorders. A literature review identified epidemiological data for each disorder. These were analysed via a Bayesian meta-regression to estimate prevalence by disorder, sex, age, location, and year. Disorder-specific prevalence was multiplied by disability weights representing the severity of health loss associated with each disorder to estimate years lived with disability (YLDs). Deaths due to anorexia nervosa were assessed with a Cause of Death Ensemble modelling strategy to estimate deaths by sex, age, location, and year, and then multiplied by the standard life expectancy at age of death to estimate years of life lost (YLLs). YLDs equalled disability-adjusted life-years (DALYs) for all mental disorders except anorexia nervosa (the only mental disorder considered as an underlying cause of death in GBD), for which DALYs represented the sum of YLDs and YLLs. We presented prevalence, deaths, YLDs, YLLs, and DALYs as counts, age-specific rates per 100 000 population, and age-standardised rates per 100 000 population. We estimated 1·17 billion (95% uncertainty interval 1·06-1·31) prevalent cases of mental disorders globally in 2023, equivalent to an age-standardised prevalence rate of 14 210·7 cases (12 849·5-15 940·1) per 100 000 population. These estimates represented a 95·5% (75·0-121·2) increase in prevalent cases and 24·2% (11·4-41·4) increase in age-standardised prevalence rate between 1990 and 2023. All mental disorders showed increases in prevalent cases between 1990 and 2023, while notable increases were seen in age-standardised prevalence rates for anxiety disorders, major depressive disorder, dysthymia, anorexia nervosa, bulimia nervosa, schizophrenia, and conduct disorder. There were an estimated 171 million (127-228) DALYs due to mental disorders globally across sex and age in 2023, equivalent to an age-standardised DALY rate of 2070·5 DALYs (1519·1-2750·5) per 100 000 population. Mental disorders contributed to 6·1% (4·8-7·6) of all-cause DALYs in 2023, making them the fifth leading cause of global DALYs (up from 12th in 1990). DALYs were almost entirely composed of YLDs. Mental disorders were the leading cause of YLDs in 2023 (up from second in 1990), explaining 17·3% (14·8-20·6) of all-cause global YLDs. Leading causes of mental disorder DALYs were anxiety disorders (ranked 11th among the 304 diseases and injuries at Level 4 of the GBD cause hierarchy), major depressive disorder (15th), and schizophrenia (41st). Globally in 2023, mental disorder age-standardised DALY rates were higher among females (2239·6 [1643·7-3014·1] per 100 000) than among males (1900·2 [1399·8-2510·8] per 100 000), and peaked in the 15-19 years age group (2617·3 [1850·6-3696·8] per 100 000). All locations showed increased mental disorder DALY rates in 2023 compared with 1990, ranging across countries and territories from 1302·4 (952·7-1683·7) per 100 000 in Viet Nam to 3555·8 (2661·9-4715·0) per 100 000 in the Netherlands. Across SDI quintiles, DALY rates ranged from 1853·0 (1352·1-2469·3) per 100 000 for middle SDI to 2184·1 (1606·1-2890·3) per 100 000 for high SDI. A significant health burden was imposed by mental disorders in all countries and territories in 2023, irrespective of the health resources available. In some instances, this burden has increased over time and is unevenly distributed across populations. Stronger surveillance systems, particularly in low-income and middle-income countries, are required. Additionally, we need more coordinated and inclusive policies to reduce the burden through early treatment and prevention, tailored to sex and age differences across locations. Responding to the mental health needs of our global population, especially those most vulnerable, is an obligation, not a choice. Gates Foundation, Queensland Health, and University of Queensland.
Nacubactam (OP0595) is a newly developed diazabicyclooctane β-lactamase inhibitor used in combination with cefepime or aztreonam. We assessed the efficacy and safety of cefepime-nacubactam and aztreonam-nacubactam versus imipenem-cilastatin in complicated urinary tract infection (cUTI) or acute uncomplicated pyelonephritis. The Integral-1 global, phase 3, multicentre, randomised, double-blind study recruited adults (aged ≥18 years) with cUTI or acute uncomplicated pyelonephritis at 79 sites in Bulgaria, China, Czech Republic, Estonia, Georgia, Japan, Latvia, Lithuania, and Slovakia. Patients were randomly assigned (2:1:1) to receive intravenous cefepime (2 g) plus nacubactam (1 g), aztreonam (2 g) plus nacubactam (1 g), or imipenem (1 g) plus cilastatin (1 g) every 8 h for 5-14 days. Randomisation was stratified by diagnosis and geographical region. The primary endpoint was the proportion of patients achieving composite clinical and microbiological success at test of cure in the microbiological modified intention-to-treat population-all patients who were randomly assigned, received any amount of the study drug, and had a baseline qualifying pathogen that was susceptible to imipenem and meropenem. The prespecified non-inferiority margin was more than 15 percentage points difference; the superiority margin was more than zero percentage points difference, for the lower bound of the two-sided 95% CI for imipenem-cilastatin. Safety was assessed in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, NCT05887908. Between May 22, 2023, and Nov 26, 2024, 614 patients were randomly assigned and 431 were included in the primary efficacy analysis (cefepime-nacubactam [n=214], aztreonam-nacubactam [n=112], or imipenem-cilastatin [n=105]); 228 patients (53%) were male and 203 (47%) were female. The primary endpoint was achieved by 176 (82%) of 214, 81 (72%) of 112, and 64 (61%) of 105 patients in the cefepime-nacubactam, aztreonam-nacubactam, and imipenem-cilastatin groups, respectively. The percentage difference in the success rate versus imipenem-cilastatin was 21·3% (95% CI 10·9 to 32·0) for cefepime-nacubactam (non-inferior and superior), and 11·4% (-1·2 to 23·7) for aztreonam-nacubactam (non-inferior). Treatment-emergent adverse events were reported in 100 (33%) of 306, 45 (30%) of 152, and 65 (43%) of 150 patients in the cefepime-nacubactam, aztreonam-nacubactam, and imipenem-cilastatin groups, respectively. No treatment-related deaths occurred. Cefepime-nacubactam and aztreonam-nacubactam are potential treatment options for Gram-negative cUTI and acute uncomplicated pyelonephritis, including infections caused by antimicrobial-resistant strains. Meiji Seika Pharma and Japan Agency for Medical Research and Development.
This study aimed to develop and optimize nanostructured lipid carriers (NLCs) to deliver venlafaxine (VLF) intranasally to optimize its brain bioavailability. The present study explores the development of an intranasal nanostructured lipid carrier-based drug delivery system for brain targeting of venlafaxine. Intranasal administration provides a noninvasive pathway for direct drug transport to the brain through the olfactory and trigeminal pathways, potentially bypassing the blood-brain barrier. Designing venlafaxine-loaded NLCs will help to increase the stability of drugs, increase the nasal residence time and provide an efficient method of delivering drugs to the brain, which is one of the promising measures toward the better treatment of depressive disorders. VLF-loaded NLCs were prepared via high-pressure homogenization and optimized using the Box-Behnken design. Glycerol monostearate and olive oil were used as lipid matrices, and Tween 80 was used as a surfactant. The physicochemical properties (particle size 112.99 nm, zeta potential -20.85 ± 2.27 mV, entrapment efficiency 94.89 ± 0.27%, drug loading 5.76 ± 0.12%) of the nanoparticles, including particle size, zeta potential, and entrapment efficiency were evaluated. In vitro release studies were conducted, followed by in vivo assessments of brain-targeting efficiency using drug-concentration analysis in brain tissues. The optimized VLF-loaded NLCs showed a particle size of 112.99 nm, zeta potential of 15.21 + 3.11 mV as well as drug entrapment efficiency of 94.89%. In vitro release showed a biphasic release profile (an initial burst release (39.7 + 0.01% in 2 h)) and a sustained release (94.56 + 1.2% in 24 h). The results of the in vivo experiments showed a significant increase in VLF concentrations in the brain tissues following administration through the intranasal route compared to administration through the oral route, and a 2.15-fold increase in Cmax, 22.5-fold larger Area Under Curve (AUC 0-), and a 9.2-h delay in Tmax (p < 0.05), indicating improved brain-targeting. The intranasal NLC system developed was able to increase the bioavailability and brain delivery of VLF with the drawback of the oral route avoided. The biphasic release profile favors the lasting therapeutic activity. This method opens a good platform of CNS drug delivery that should be pursued by additional pharmacokinetic and clinical research.
This review systematically summarizes the mechanisms and applications of friction as both endogenous and exogenous stimuli in drug delivery systems (DDSs). Intelligent DDS can respond to endogenous or exogenous stimuli to achieve accurate drug delivery, so it has become a hot spot in pharmaceutical research. Therefore, friction, as a novel physical stimulus, offers unique potential to overcome physiological barriers and improve targeted therapy, providing new strategies for DDS design. This article systematically reviews the two forms of stimulation of friction in drug delivery and its mechanism. In terms of endogenous effects, the focus was on exploring the regulatory effects of physiological friction, such as biological friction shear, cellular micro friction, eyelid corneal friction, and joint friction on drug delivery, revealing how frictional stimulation triggers drug release or enhances targeting through mechanical signals. In terms of exogenous effects, the promoting mechanism of mechanical friction on transdermal DDSs and the intracellular drug delivery technology driven by frictional nanogenerators were analyzed. This review outlines friction-triggered drug release mechanisms and their therapeutic potential, highlighting superior spatiotemporal precision for dynamic tissues over traditional systems, yet notes key translational challenges including parameter standardization and drug-device integration. Friction, as a unique endogenous/exogenous stimulus, enables highly precise drug delivery. Advancing clinical translation requires establishing biotribological quantitative models, developing responsive biomimetic materials, and promoting integrated 'drug‑device' development through multidisciplinary collaboration.
Acne is a common inflammatory disease of the hair follicles and sebaceous glands, but most of the current treatments have side effects or drug resistance problems. This study developed a stable, self-emulsifying composite Microemulsion (PHS-ME) co-loaded with paeonol, honokiol and Salix alba (white willow) bark extract. The formulation was optimized using Box-Behnken design. Physicochemical properties, centrifugation and storage stability (35 days at 4 °C, 25 °C, and 40 °C), in vitro drug release, cytotoxicity (HaCaT cells), cellular uptake, anti-inflammatory activity (LPS-stimulated RAW264.7 cells), and antibacterial efficacy against Cutibacterium acnes and Staphylococcus aureus were evaluated. PHS-ME exhibited a uniform spherical morphology with a mean droplet size of 13.54 ± 0.35 nm, high encapsulation efficiency, and excellent physical stability. It showed sustained drug release, good biocompatibility (safe up to 8 µg/mL). Finally, PHS-ME significantly enhanced the cellular uptake of HaCaT and effectively inhibited the production of key inflammatory mediators in RAW264.7. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of the composite Microemulsion against Cutibacterium acnes and Staphylococcus aureus for acne were the same, which were 0.5 mg/mL and 2 mg/mL respectively. This study proposes a simple and stable strategy for preparing composite Microemulsion. Due to its synergistic anti-inflammatory and antibacterial properties, these Microemulsions have great industrial potential as a natural local anti-acne product.
Prednisolone's poor aqueous solubility limits its oral bioavailability, necessitating the development of innovative formulation strategies. This study aimed to extract AX from ispaghula husk and develop AX-based spray-dried microspheres to improve prednisolone dissolution. AX was extracted from ispaghula husk, and its molecular weight was determined using gel permeation chromatography. Prednisolone-loaded AX microspheres (F1-F4) were prepared by spray drying and evaluated for drug loading, entrapment efficiency, and product yield. Structural and physicochemical characterization was performed using NMR, FTIR, SEM, and DSC. In vitro dissolution studies were conducted over 60 min. Initial and relative dissolution rates, along with similarity factor (f2) analysis, were used to compare formulations. Drug loading ranged from 3.7 to 15.63% w/w, with the highest values observed for F3 and F4. Entrapment efficiency increased with drug loading, ranging from 15.85% (F1) to 36.43% (F4), while product yield ranged from 52.4 to 63.1% w/w. NMR confirmed drug stability following spray drying. SEM revealed irregular, rough-surfaced microspheres and reduced drug particle size. FTIR demonstrated drug-polymer compatibility, and DSC indicated drug amorphization. Formulations F3 and F4 achieved >72% dissolution within 60 min, exceeding pure prednisolone (26.8%) and the commercial tablet (49.9%). Similarity factor analysis indicated that F1 was closest to the marketed product, whereas F3 and F4 exhibited superior dissolution rates. Spray-dried AX microspheres significantly enhanced prednisolone dissolution, highlighting AX as a biocompatible, scalable, and promising excipient for poorly water-soluble drugs.
The objective of this review is to critically evaluate the potential of co-amorphous solid dispersions (CASDs) in improving the performance of poorly soluble active pharmaceutical ingredients (APIs). CASDs are being scoped in this review because limited aqueous solubility remains a persistent challenge in drug development, particularly for Biopharmaceutics Classification System (BCS) Class II and IV drugs, where poor solubility restricts oral bioavailability and clinical translation. This review highlights the mechanistic aspects underlying enhanced bioavailability, phase behavior, and key molecular interactions that support the effectiveness of CASDs. Evidence from case studies demonstrates the use of diverse co-formers, including amino acids, organic acids, other APIs, and novel systems such as poly (amino acids) and flavonoids. Preparation methods, with emphasis on green and continuous manufacturing approaches such as spray drying, thermal, and mechanical activation, are discussed alongside advanced spectroscopic and computational characterization techniques. Reported outcomes consistently show improvements in solubility, dissolution, and pharmacokinetic properties, while regulatory perspectives and the application of Process Analytical Technology (PAT) illustrate pathways toward clinical adoption. CASDs represent a versatile platform with implications for personalized medicine, artificial intelligence (AI)-driven formulation design, and multifunctional co-formers though challenges in stability, scalability, and regulatory navigation remain priorities for future research.
The review aims to systematically explore the transformative impact of artificial intelligence (AI) on pharmaceutical sciences. It addresses key research questions regarding how AI accelerates drug development, enhances clinical trial design, optimizes manufacturing, and drives advances in personalized and precision medicine. A comprehensive literature review was conducted. It synthesized recent studies, industry reports, and regulatory guidelines on AI adoption. Covered drug discovery, clinical trials, pharmacovigilance, manufacturing, supply chain management, and pharmacy education. It also critically examined barriers such as data quality, privacy, explainability, and the evolving regulatory landscape. AI accelerates pharmaceutical R&D, identification, lead optimization, ADMET (absorption, distribution, metabolism, excretion, toxicity) prediction, drug repurposing, and clinical trial analytics. It enables faster and more cost-effective development. Advancements in personalized medicine and individualized patient data are driving better patient outcomes. The students still ace continuing challenges in data interpretation, privacy, and regulatory issues. Ongoing AI advancements and evolving regulations are set to revolutionize pharmaceutical science. They will enable efficient, predictive, and patient-centered healthcare. Success will depend on integrating multi-omics, adopting explainable AI, and fostering collaboration among all stakeholders. Ultimately, AI promises safer, faster, and more precise drug delivery system. It benefits clinicians, researchers, and students.
To systematically review the structural characteristics, release mechanisms, and stability challenges of solid dispersions (SDs), identifying key determinants of physical instability and summarizing emerging stabilization strategies. This review compares various stabilization approaches, highlighting their optimal applications and limitations to support broader SD market translation. The generational evolution, structural features, and characterization techniques of SDs are outlined, along with the spring-parachute dissolution mechanism. Four major drivers of physical instability are identified: preparation-related parameters, humidity-induced phase separation, kinetic factors, and thermodynamic factors. Recent stabilization strategies-including ternary SD systems, drug loading control, and in vivo performance enhancement-are discussed. Emerging physicochemical descriptors and predictive models for rational formulation design are also summarized. SD technology remains critical for improving bioavailability of poorly water-soluble drugs, but broader translation is limited by system-dependent stability, inefficient excipient screening, high-dose formulation challenges, and limited predictive dissolution models. Future progress requires integrating formulation design, process engineering, and predictive modeling, including multifunctional polymers, advanced manufacturing (e.g. hot-melt extrusion), and digital tools based on molecular simulation and AI. Establishing biorelevant evaluation systems and robust in vitro-in vivo correlation (IVIVC) models is essential to bridge laboratory research and clinical application.
Allergic conjunctivitis is one of the most prevalent conditions affecting the eyes, and various medications are used in its treatment. In this study, olopatadine and verbascoside were used in combination. A factorial design was employed to evaluate the effects of Poloxamer 407 and sodium alginate. The impact of polymer concentration on parameters such as viscosity, gelation time, mucoadhesion, pH, and gelation temperature - considered indicators of ideal formulations - was assessed. The optimal formulation, determined through the factorial design, included 0.5% sodium alginate and 20% poloxamer 407. The obtained values were viscosity at 25 °C = 7451.8 cP, viscosity at 35 °C = 11367.3 cP, pH = 7.12, gelation temperature = 30 °C, gelation time = 52 s, and mucoadhesion = 0.301 N. Cytotoxicity tests on ARPE-19 and L929 cells, along with irritation studies, indicated acceptable safety profiles. In vitro release tests demonstrated an initial burst release of verbascoside and olopatadine during the first 2 h, followed by a controlled release over the subsequent 8 h. Mathematical analysis of the release kinetics revealed a good fit with the Weibull model. No adverse effects were observed in rats during Draize's in vivo test. Consequently, the drug-loaded in situ gel formulation may be a promising option for treating allergic conjunctivitis.
To analyze the extensive literature underlying the concept of using and formulating Orodispersible tablets (ODTs) for managing psychiatric and mood disorders. Psychiatric and mood disorders represent a major global health burden across all age groups, significantly impairing quality of life and daily functioning. Emotional distress associated with these conditions often leads to poor medication adherence and difficulty swallowing, particularly in vulnerable populations. Thus, an increased emergency intervention is required during acute panic or agitation states. ODTs have emerged as a patient-oriented, rapidly disintegrating oral drug delivery system. It enhances treatment adherence and facilitates faster therapeutic action, especially during acute psychiatric episodes. ODTs offer distinct advantages for antipsychotics, antidepressants, anxiolytics, and mood stabilizers by modulating pharmacokinetic and pharmacodynamic profiles based on the drug's Biopharmaceutics Classification System (BCS). Recent advances in three-dimensional (3D) printing, nanotechnology, and smart polymer systems have expanded the potential of ODTs. These technologies can effectively address key formulation challenges such as dose loading, poor solubility, moisture sensitivity, and taste masking, and ensure personalized dosing strategies. In parallel, the application of Quality by Design (QbD) and systematic optimization approaches allows the development of robust ODT formulations with adequate mechanical strength, rapid disintegration, and consistent performance. The rational development and clinical translation of tailored psychiatric ODTs for patients require adherence to established regulatory frameworks to ensure product quality, safety, efficacy, and patient acceptability.
Asparagus stipularis Forssk decoction (ASD) has shown potential metabolic and antioxidant benefits, yet its effects on pancreatic dysfunction associated with metabolic syndrome remain insufficiently explored. The aim of this work was to assess the pancreatic protective properties of ASD in high-fructose diet (HFrD)-fed rats and to characterize ASD-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) as a delivery system to enhance its therapeutic potential. Rats were fed an HFrD and treated with ASD at two dose levels. Serum α-amylase and lipase activities were measured to assess digestive enzyme modulation. Pancreatic lipid peroxidation was quantified using thiobarbituric acid reactive substances (TBARS), while antioxidant enzyme activities, including superoxide dismutase, catalase, and glutathione peroxidase, were determined. Histopathological examination was performed to evaluate structural alterations in pancreatic tissues. ASD was encapsulated into PLGA NPs, and particle size, polydispersity index (PdI), zeta potential (ZP), and encapsulation efficiency (EE) were analyzed. ASD significantly reduced serum α-amylase activity to 2285.3 ± 256.6 U/L (low dose) and 1846.4 ± 82.8 U/L (high dose) compared to HFrD controls. Serum lipase activity decreased by 13% and 18% at the respective doses. TBARS levels were markedly reduced, and antioxidant enzyme activities were restored to near-control levels. Histological analysis revealed improved β-cell morphology and reduced acinar degeneration. ASD-loaded PLGA NPs exhibited a mean size of 248 ± 5 nm, PdI of 0.13 ± 0.01, ZP of -24.7 ± 1.3 mV, and an EE of 75.5 ± 3.2%. ASD demonstrates significant pancreatic protective effects, and nanoencapsulation enhances its therapeutic promise for metabolic disorders.
Carbon nanotubes (CNTs) have emerged as non-viral gene delivery vectors, due to their physicochemical properties, high surface area, anisotropic needlelike geometry, tunable surface chemistry, and unique optical and thermal characteristics. This review synthesizes mechanistic understanding of CNT-mediated gene delivery: cellular uptake, receptor-mediated targeting through surface functionalization, and the challenge of endosomal escape. Understanding how CNTs enter cells, behave intracellularly, and what determines functional therapeutic outcomes is essential for advancing their clinical development. We detail four primary endosomal escape mechanisms: direct cell membrane translocation through intrinsic needlelike property or with cell-penetrating peptide (CPP) facilitation, the proton sponge effect from polyamine coatings, and photothermal/photochemical internalization. We also compare their efficiency against lipid nanoparticle (LNP) and polymeric vector. We further examine CNT's intracellular fate, covering protein corona formation, complement pathway activation and its immune consequences, macrophage recognition, and biodegradation. Intracellular fate trajectories are linked to measurable functional outcomes. Lysosomal sequestration governs their silencing potency, tumor tissue pharmacokinetics determine knockdown duration, and CNS biopersistence coincides with sustained microglial activation. An immunotoxicological evaluation framework adapted from established NCL and regulatory guidelines (ISO/TS 10993-20, ISO/TR 10993-22, ICH S8) is outlined, encompassing complement split product quantification, PBMC cytokine profiling, inflammasome activation assays, and in vivo immunophenotyping. Translational obstacles remain. Including biopersistence, unpredictable protein corona composition, cytotoxicity, and the absence of standardized manufacturing and characterization protocols. Emerging stimuli-responsive hybrid nanostructures and AI-assisted design offer promising pathways forward, contingent on coordinated progress in reproducible manufacturing, longitudinal fate monitoring, and rigorous immunotoxicological assessment.
Odontalgia (Tooth pain) involves inflammation and infection, requiring anti-inflammatory and antibacterial agents to manage pain. Conventional gels containing NSAIDs, topical anesthetics, and antibacterial agents, individually or in combination, are not very effective due to rapid saliva washout, thereby necessitating frequent re-dosing. As there are no oral in-situ gels containing anti-inflammatory and antibacterial agents available in the market for odontalgia, an in-situ gel containing meloxicam (prostaglandin inhibitor), thereby providing an anti-inflammatory effect, and chlorhexidine (antibacterial) was formulated for localized dual-action and prolonged contact at the targeted area. As there are no reported HPLC methods for the simultaneous estimation of meloxicam and chlorhexidine, an analytical quality-by-design-based reverse-phase high-performance liquid chromatography method was developed for the simultaneous quantification of both drugs in the formulated in-situ gel. Taguchi screening design analyses the influence of key chromatographic parameters on method performance. A Box-Behnken design was used to generate the trial runs. The final method utilized a Cosmosil 5 C18-MS-II column with an isocratic mobile phase consisting of an aqueous phase containing 0.025% orthophosphoric acid and acetonitrile in 20:80% v/v ratio, flow rate (1.0 mL/min), injection volume (10 μL) at a detection wavelength of 289 nm. The developed method was validated as per ICH Q2(R1) guidelines. The assay value was calculated and found to be 98.53% for MLX and 99.02% for CHX. The validated method applied for the quantitative analysis of meloxicam and chlorhexidine in the formulated in-situ gel.
To formulate and evaluate a pregabalin-loaded transferosomal gel for transdermal delivery aimed at, improving skin penetration, sustaining drug release, and increasing patient compliance in the management of peripheral neuropathy. Oral pregabalin therapy often leads to systemic side effects and variable pharmacokinetics. A transferosome-based gel offers a novel approach to improve dermal penetration, prolong drug release, and reduce systemic exposure, potentially enhancing therapeutic outcomes in neuropathic pain. Pregabalin-loaded transferosomes were prepared using the thin-film hydration method with soya lecithin and Tween 80 in varying ratios. Formulations were evaluated for particle size, polydispersity index, zeta potential, entrapment efficiency, and morphology. The optimized formulation was incorporated into a gel and assessed for pH, drug content, in vitro drug release, ex vivo permeation through goat ear skin, irritancy using the hen's egg test on the chorioallantoic membrane, and stability for 90 days. The vesicles displayed particle sizes of 378.9-1471 nm, a PDI of 0.3-0.8, and a zeta potential from -17.2 to -31.6 mV. Entrapment efficiency[ee] ranged from 40.35% to 89.2%. Scanning electron microscopy confirmed smooth, spherical vesicles. The transferosomal gel showed pH 5.2-6.1 and drug content of 93.4%-98.8%. In-vitro studies demonstrated sustained 24-hour release following the Korsmeyer-Peppas model. Ex-vivo permeation showed 92.2% permeation, a flux of 467.18 µg/cm2/h, and a lag time of 0.99 h. The gel was nonirritant and stable for 90 days. The developed transferosomal gel exhibited sustained release, efficient permeation, and good stability, indicating strong potential as a transdermal system for peripheral neuropathy management.
To study the synergistic anticancer efficacy of Andrographolide (AG), a bioactive phytochemical with immunomodulator properties, and paclitaxel (PTX), a frontline chemotherapeutic agent, when administered as co-loaded nanoemulsion, to enhance therapeutic outcome with minimal adverse effect. The proposed nanoemulsion is expected to achieve synergistic anticancer effects, and minimize systemic toxicity. Cytotoxic potential of AG and PTX at various molar concentrations using Chou-Talalay method were determined. A synergistic ratio (1:1) was identified and used as coloaded nanoemulsion. The system was optimized for particle size, zeta potential and encapsulation efficiency. Thermal and spectral characterization techniques were employed to evaluate drug identity and compatibility, while HPLC-based analytical method was developed for simultaneous quantification of AG and PTX in % entrapment and drug release samples. Further evaluated for MTT test, cell uptake study, scratch migration test, apoptosis and cell cycle arrest. Tumor regression test confirmed therapeutic efficacy and acute toxicity test ensure the safety of developed formulation. The AG-PTX nanoemulsion exhibited enhanced cellular uptake, cell apoptosis, and cell-cycle arrest in vitro compared to monotherapies. In vivo studies using a syngeneic tumor (invasive mammary carcinoma) bearing mouse model demonstrated significant tumor regression (10-fold), improved and reduced systemic toxicity, as shown by stable body weight and histopathological assays. Co-delivery of AG and PTX via targeted nanocarrier offers a promising dose reduction strategy to circumvent the dose limiting toxicity of PTX while maintaining/enhancing its anticancer efficacy. Further, the findings suggest a translational potential for AG as a chemosensitizer in combination therapy regimens.
Restrictions on antibiotic growth promoters in poultry production have driven the search for safe, natural alternatives. Organic acids, herbal additives and spirulina are promising options due to their antimicrobial, antioxidant and growth-enhancing effects. The purpose of this experiment was to evaluate the effects of formic acid (FAc), herbal mixture (HMX) and spirulina powder (SPI) as potential antibiotic alternatives in broiler diets, specifically examining their impact on growth, carcass characteristics, blood biochemistry and intestinal microbial count. Six replicates of ten unsexed chicks per group comprised the eight experimental groups to which 480 one-day-old Ross 308 broiler chicks were randomly assigned. The treatments were as follows: T1 (control); T2 (0.5 g Colistin antibiotic/kg diet); T3 (2 cm3 FAc/kg diet); T4 (4 cm3 FAc/kg diet); T5 (2 g HMX/kg diet); T6 (3 g HMX/kg diet); T7 (0.5 g SPI/kg diet); and T8 (1 g SPI/kg diet). Significant differences were detected in daily body weight gain (DBWG) and live body weight (LBW), with the spirulina-treated groups (T7 and T8) showing the highest values. Also, significant influences on feed intake (FI), feed conversion ratio (FCR) and performance index (PI), with the HMX groups showing the most favourable FCR and the highest PI. Blood biochemistry and antioxidant markers were influenced by the HMX and SPI treatments. The SPI groups showed reduced liver enzyme levels, while the HMX groups demonstrated improved protein profiles and enhanced antioxidant enzyme activity. Microbial analysis revealed that FAc and HMX treatments led to a reduction in pathogenic bacteria, with T3, T4 and T5 showing the lowest levels of Escherichia coli and Salmonella. These results suggest that FAc, HMX and SPI are promising dietary supplements for enhancing both the broiler chickens' growth rates and general health.
The increasing anthropogenic burden, driven by population growth and intensified industrial and agricultural practices, has led to the widespread release of endocrine-disrupting chemicals (EDCs) into aquatic ecosystems, with significant implications for both environmental and human health. Many studies have reported the concentrations and toxicological effects of EDCs in aquatic environments, but few have addressed detection methods and remediation techniques. This review aims to highlight the sources, dynamics, and bioaccumulation of EDCs in aquatic ecosystems, along with their toxic effects on aquatic species and associated health risks in humans. Additionally, we provide an overview of advanced detection and remediation techniques. Our review found that EDCs, particularly phthalates and bisphenols, included in industrial effluents, domestic waste, and agricultural runoff, are frequently discharged into aquatic bodies through human activities. EDCs are associated with various toxic effects in aquatic organisms, such as bioaccumulation, transgenerational effects, reduced growth, immunotoxicity, DNA damage, and abnormal hormonal release, which impair reproductive development. Among the detection methods, biosensors, surface-enhanced Raman spectroscopy (SERS), and nuclear magnetic resonance (NMR) spectroscopy are promising tools for EDC detection relative to conventional analytical methods in aquatic systems. Emerging remediation techniques, such as hybrid activated carbon systems and N-doped carbon-based adsorbents, are recommended for their high removal efficiency. This review serves as a valuable resource for advancing research on EDC toxicity, detection, and remediation technologies. 在人口增长及工农业生产加剧的推动下，日益增加的人类活动促使内分泌干扰物（EDCs）被广泛释放到水生态系统中，对环境和人类健康产生了重大影响。已有诸多研究报道了EDCs在水环境中的浓度及其毒理学效应，但关于其检测方法和修复技术的研究仍然较少。本综述旨在系统阐述水生态系统中EDCs的来源、动力学和生物累积特征，并分析其对水生物种和人类健康的毒理学影响。此外，本综述还概述了先进的检测和修复技术。结果发现，EDCs（特别是邻苯二甲酸盐和双酚）常跟随工业废水、生活垃圾和农业径流经人类活动被排放到水体中。EDCs与水生生物的各种毒性效应密切相关，包括生物累积、跨代效应、生长减缓、免疫毒性、DNA损伤和异常激素释放，进而损害水生生物的生殖和发育功能。在检测技术方面，相比于传统方法，生物传感器、表面增强拉曼光谱和核磁共振光谱被认为是水环境中EDCs检测最具前景的三种技术。在新兴修复技术中，混合活性炭系统和氮掺杂碳吸附剂因其高效的去除能力而备受青睐。总之，本综述为促进水生态系统中EDCs的毒性机制研究，以及推动检测和修复技术发展提供了宝贵的参考资料。.
This study focused on improving the delivery of tectoridin, an anti-alcoholic compound from Pueraria flower, which suffers from poor solubility and low bioavailability when taken orally. To address this, we designed a biomimetic liposome system that targets the liver by harnessing the body's natural bile acid transport pathways. Successful clinical translation of many insoluble natural products, including tectoridin, is limited by their unfavorable pharmacokinetics. A liver-targeted strategy utilizing physiological transporters offers a promising means to enhance hepatic delivery and therapeutic efficacy, thereby addressing a critical hurdle in the development of plant-derived pharmaceuticals. Following bioactivity-guided isolation and identification of tectoridin, cholic acid-functionalized liposomes (LPs-tectoridin) were designed to actively target hepatocyte-specific transporters (NTCP/OATPs). The formulation was optimized and characterized for particle size, encapsulation efficiency, and in vitro dissolution. Pharmacokinetic, tissue distribution, and pharmacodynamic evaluations were performed in a rat model of ethanol-induced intoxication and liver injury. The optimized liposomes exhibited a mean particle size of 157.55 ± 0.23 nm, a high encapsulation efficiency (>85%), and significantly improved the dissolution rate of tectoridin. In vivo, LPs-tectoridin increased the oral bioavailability (AUC0-24) by 2.11-fold and enhanced hepatic accumulation by 3-fold compared to free tectoridin. The formulation demonstrated superior anti-intoxication and hepatoprotective effects, notably reducing serum ALT and AST levels by 49.95% and 35.20%, respectively, and elevating hepatic SOD activity by 2.04-fold. This study not only confirms tectoridin as a principal anti-alcoholic constituent but also establishes a robust liver-targeted liposomal platform that harnesses intrinsic bile acid transport pathways. The strategy significantly improves the solubility, bioavailability, and therapeutic performance of tectoridin, offering a viable approach for enhancing the delivery of poorly soluble natural products in drug development.
This study aims to develop and assess Naringenin-loaded niosomal vaginal in situ gel for the effective management of Polycystic Ovary Syndrome. The objectives include enhancing drug permeation, ensuring sustained release and mitigating the oral side effects associated with naringenin. Naringenin-loaded niosomes were formulated by ethanol injection method and a 33Box-Behnken design (DESIGN EXPERT® Software) with five center points was generated, yielding 17 experimental runs. They were characterized for globule size, percent entrapment efficiency, zeta potential, and polydispersity index. The optimized batch was incorporated into the in situ gel. Vaginal irritancy and in vivo studies were conducted in female Wistar rats to evaluate the therapeutic efficacy of the prepared formulation in the treatment of Polycystic Ovary Syndrome. An 18% concentration of Pluronic F-127 was identified as optimal for gel formulation, and various evaluations, including in vitro drug release, diffusion studies, in vivo vaginal irritancy, histopathological analysis and short-term stability studies, were performed. The optimized niosomal formulation exhibited a vesicle size of 158.1 nm, an entrapment efficiency of 71.68%, a zeta potential of -28.6 mV and a drug content of 70.79 ± 1.95%. Transmission Electron Microscopy confirmed the nanoscale globule size, while the in vitro drug release rate for the niosomal formulation was 74.104%. The gel showed a viscosity range from 192.71 ± 1.23 cps to 1756.43 ± 7.46 cps as the temperature increased from 25 ± 2.0 °C to 38 ± 2.0 °C. In vitro diffusion studies showed 84.67% drug release. In vivo administration of the Naringenin loaded niosomal vaginal gel markedly lowered body weight and fasting blood glucose (p < 0.001) and reestablished hormonal, lipid, and antioxidant homeostasis by decreasing serum testosterone, triglycerides, total cholesterol, and low-density lipoprotein, while elevating progesterone, high-density lipoprotein, superoxide dismutase, catalase, and glutathione levels along with a concurrent decline in malondialdehyde (p < 0.001). Histopathological findings demonstrated fewer cystic follicles, restored folliculogenesis, and normalized adipocyte structure, and vaginal irritancy assessments verified the formulation's safety and therapeutic effectiveness against mifepristone-induced Polycystic Ovary Syndrome. Short-term stability studies demonstrated the optimized formulation's stability at 4 °C. The Naringenin-loaded niosomal vaginal in situ gel offers significant potential in managing PCOS with enhanced drug delivery and safety profiles.