Search Results (417)

Sertaconazole nitrate (SN), a broad-spectrum antifungal agent, is clinically employed against diverse dermatophyte infections. Its therapeutic efficacy, however, is constrained by poor aqueous solubility (0.006 mg/mL) and insufficient skin penetration from current commercial formulations. To address these limitations, this research focused on developing, optimizing (using a 3² factorial design), and assessing a topical nanovesicular gel incorporating sertaconazole nitrate-loaded ultraflexible liposomes (SN-UFLs) to enhance antifungal performance. The vesicles exhibited near-spherical morphology, with sizes ranging from 104.40 ± 1.20 to 151.90 ± 2.14 nm, zeta potential (ZP) values between −21.50 ± 1.25 and −51.20 ± 2.25 mV, and entrapment efficiency (EE) values from 77.60 ± 2.50% to 86.04 ± 3.20%. The optimized SN-UFL formulation (OPT-SN-UFL) was then integrated into a carbopol gel base. This SN-UFL-Gel was characterized for pH (6.5 ± 0.20), viscosity (499.66 ± 15 cP), spreadability (205 ± 1.50%), extrudability (154.18 ± 2.48 g/cm²), and drug content (96.7 ± 2.50%), as well as ex vivo skin permeation, skin irritation potential, and in vitro and in vivo antifungal efficacy. Compared with the marketed formulation, higher drug permeation and skin deposition were observed for SN-UFL-Gel. The SN-UFL-Gel exhibited a larger zone of inhibition (25 ± 1.50 mm) against Candida albicans compared to the commercially available formulation (20 ± 1.72 mm). The in vivo animal studies showed that SN-UFL-Gel showed better antifungal activity by efficient inhibition of infection induced in rats with Trichophyton mentagrophytes. The SN-UFL-Gel showed no signs of skin irritation and was stable at 4 ± 1, 25 ± 2, and 40 ± 2 °C for 3 months. Conclusively, the current work divulged successful augmentation of the overall effectiveness of sertaconazole nitrate by using deformable liposomes as a promising nanocarrier. Full article

Background: Tetrabenazine, a VMAT2 inhibitor used for hyperkinetic disorders, shows considerable pharmacokinetic variability due to extensive first-pass metabolism. Standardization of clinical trial conditions, including posture, may reduce variability and improve bioequivalence assessments. Objective: The aim of this study was to determine the impact of postural restriction on the pharmacokinetics of tetrabenazine and its active metabolite, dihydrotetrabenazine (HTBZ), under controlled conditions. Methods: A randomized, open-label, four-period replicate crossover study enrolled 72 healthy fasted adults who received a single 25 mg tetrabenazine dose under two conditions: 4 h semirecumbent posture versus unrestricted movement. Plasma drug concentrations were measured across 36 h using validated LC–MS/MS method. Pharmacokinetic parameters were estimated via non-compartmental analysis and compared with Wilcoxon signed-rank tests. Results: Postural restriction significantly increased tetrabenazine exposure (AUC_0–t: +16.4%, p < 0.0001) and half-life (p = 0.002), with a nonsignificant rise in C_max. For HTBZ, C_max decreased (−16.2%, p = 0.018), whereas AUC was unchanged. Parent-to-metabolite ratios increased by 24–29%. Replicate design analyses showed reduced intra-subject variability for tetrabenazine AUC with posture control (~24% vs. >28%). Simulation suggested that posture restriction could lower sample size requirements by 15–30% in two-period average bioequivalence trials. Conclusions: Maintaining a semirecumbent posture after dosing enhances tetrabenazine’s bioavailability, attenuates early metabolite formation, and reduces pharmacokinetic variability. Incorporating posture control into bioequivalence trial protocols may optimize study design, reduce participant exposure, and align with ICH-GCP ethical principles. Full article

Background: Epigallocatechin-3-gallate (EGCG), a potent green tea polyphenol, possesses significant therapeutic potential, but its clinical application is limited by poor gastrointestinal stability and low oral bioavailability. To address this, a novel herbal nanomedicine-based delivery system was developed utilizing D-α-tocopheryl polyethylene glycol succinate (TPGS) and Poloxamer 407. Objectives: This study aims to develop and characterize EGCG-loaded TPGS/Poloxamer 407 micelles, evaluating their physicochemical properties, storage stability, in vitro drug release profile, in vivo oral bioavailability, and preliminary tolerability observation. Methods: The micelles were prepared using the film hydration method followed by lyophilization. Results: The optimized 2:2 TPGS-to-poloxamer 407 weight ratio yielded EGCG-loaded micelles, displaying a mean particle size of 15.4 nm, a polydispersity index (PDI) of 0.16, a zeta potential of −17.7 mV, an encapsulation efficiency of 82.7%, and a drug loading capacity of 7.6%. The critical micelle concentration (CMC) was determined to be 0.00125% w/v. Transmission electron microscopy (TEM) confirmed the micelles’ uniform spherical morphology. In vitro release studies demonstrated a sustained release profile in both simulated gastric and intestinal fluids. EGCG formulation remained stable for at least six months when stored at 4 °C. No adverse clinical signs were noted during the 28-day tolerability observation. In vivo pharmacokinetic evaluation in mice revealed a significant elevation in oral bioavailability, achieving a 2.27-fold increase in area under the curve (AUC) and a 1.8-fold increase in peak plasma concentration (Cmax) compared to free EGCG. Conclusions: Collectively, these findings underscore the potential of the TPGS/poloxamer 407-based micelle system as a promising oral delivery platform for EGCG, enhancing its stability and pharmacokinetic performance. Full article

Hydrogel microneedles (HMNs) act as non-invasive devices that can effortlessly merge with the human body for drug delivery and diagnostic purposes. Nonetheless, their improvement is limited by intricate and repetitive issues related to material composition, structural geometry, manufacturing accuracy, and performance enhancement. At present, there are only a limited number of studies accessible since artificial intelligence and machine learning (AI/ML) for HMN are just starting to emerge and are in the initial phase. Data is distributed across separate research efforts, spanning different fields. This review aims to tackle the disjointed and narrowly concentrated aspects of current research on AI/ML applications in HMN technologies by offering a cohesive, comprehensive synthesis of interdisciplinary insights, categorized into five thematic areas: (1) material and microneedle design, (2) diagnostics and therapy, (3) drug delivery, (4) drug development, and (5) health and agricultural sensing. For each domain, we detail typical AI methods, integration approaches, proven advantages, and ongoing difficulties. We suggest a systematic five-stage developmental pathway covering material discovery, structural design, manufacturing, biomedical performance, and advanced AI integration, intended to expedite the transition of HMNs from research ideas to clinically and commercially practical systems. The findings of this review indicate that AI/ML can significantly enhance HMN development by addressing design and fabrication constraints via predictive modeling, adaptive control, and process optimization. By synchronizing these abilities with clinical and commercial translation requirements, AI/ML can act as key facilitators in converting HMNs from research ideas into scalable, practical biomedical solutions. Full article

Background/Objectives: Pharmaceutical cocrystallization offers a promising strategy to enhance drug properties while preserving molecular integrity. Ezetimibe, a BCS Class II hypolipidemic agent, faces therapeutic limitations due to poor aqueous solubility. This study aimed to systematically evaluate cocrystallization of ezetimibe with organic acid (benzoic, tartaric, or succinic acid) at varying stoichiometric ratios (1:0.5–1:2) to optimize physicochemical properties and oral bioavailability. Methods: Cocrystals were prepared via solvent evaporation (SEV) and solvent/anti-solvent (SAS) methods. Structural characterization included Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and powder/single-crystal X-ray diffraction (PXRD/SCXRD). Physicochemical performance was assessed through saturation solubility, in vitro dissolution, and in vivo pharmacokinetics in male Sprague Dawley rats (n = 4/group). Results: Benzoic acid cocrystals (1:2 ratio, SEV) showed O−H⋯N hydrogen bonding (FTIR band shifts: 2928 → 3264 cm⁻¹) and novel crystalline phases (12.4°, 16.7°, and 24.9°). SCXRD confirmed monoclinic P2₁/n symmetry (a = 5.42 Å, b = 5.05 Å) for benzoic acid cocrystals. Ezetimibe/benzoic acid cocrystals (1:2) achieved 64-fold solubility enhancement and 2× faster dissolution vs. pure ezetimibe. Pharmacokinetics revealed 3× higher Cmax (18.38 ng/mL) and 4× greater AUC (40.36 h·ng/mL) for optimized cocrystals. Tartaric and succinic acid cocrystals showed moderate improvements, with melting points intermediate between parent compounds. Conclusions: Both stoichiometry and preparation method strongly determined cocrystal performance. Benzoic acid at a 1:2 ratio via SEV demonstrated superior solubility, dissolution, and bioavailability, addressing ezetimibe’s formulation challenges. These findings underscore the potential of rational cocrystal design to overcome solubility barriers in oral dosage development, particularly for hydrophobic therapeutics. Full article

Background/Objectives: As safe, eco-friendly, and legally compliant solutions for the disposal of unwanted medications, drug take-back systems have attracted extensive research attention. However, there is a lack of systematic mapping of global trends, collaborative networks, research themes, and hotspots in this field. This study aimed to conduct a comprehensive bibliometric analysis and review of global academic research on drug take-back programs. Methods: Peer-reviewed research articles on drug take-back programs, published between 2005 and 2025, were retrieved from the Web of Science Core Database. Microsoft Office Excel 2019, VOSviewer (v.1.6.17), and CiteSpace (v.6.1.R3 Advanced) were used to assess publication/citation trends, countries, institutions, authors, journals, disciplines, references, and keywords. Narrative analysis was employed to synthesize data from the included articles and identify core research themes. Results: A total of 149 eligible articles with 4520 citations were included, involving 619 authors, 52 countries/regions, 310 institutions, and 95 journals. Publication/citation counts increased significantly between 2005 and 2025. The United States led in both publication output and collaborative research; Mercer University was the most influential institution, but international and cross-institutional collaboration remained limited. Environmental Sciences ranked first among disciplinary categories in drug take-back research, followed by Pharmacology/Pharmacy. Core research themes underpinning this field included stakeholders’ knowledge–attitude–practice assessment (76 articles), returned medication treatment (37 articles), intervention evaluation (25 articles), policy analysis (7 articles), and the role of drug take-back programs in mitigating environmental and public health hazards caused by medicine wastes (4 articles). Conclusions: Scholarly attention to drug take-back programs has grown steadily. Future research should prioritize cross-sectoral and international cooperation, develop and adopt evidence-based interventions to optimize the safety, sustainability, and accessibility of drug take-back systems on a global scale. Full article

Objectives: The purpose of this study was to analyze the effect of daily intake of cladribine tablets on the course of multiple sclerosis (MS) while monitoring for 1–4 years during and after the course in several neurological clinics from different regions of the Russian Federation. Materials and Methods: Information was collected on 235 patients from 12 neurological clinics and regional centers for MS, who were observed for an average of 3.4 years after starting treatment with cladribine. Results: An independent analysis of cases of prescription of cladribine in tablets showed that the reason for prescription of cladribine was highly active MS (HAMS) in 159 patients (67.7%), rapidly progressive MS (RPMS) in 20 patients (8.5%), active remitting MS in 50 patients (21.3%) and secondary progressive MS (SPMS) with exacerbations in 6 (2.5%). Among them, only 12 patients (5.1%) had not previously received DMTs, i.e., in these cases, the drug was prescribed as the first DMT. In total, 22 patients had previously received natalizumab, 5—ocrelizumab, and in 1 case—fingolimod. The remaining 207 patients were crossed over from the first-line DMTs. In all cases, there was a decrease in the frequency of exacerbations during and after the completion of the course of cladribine. Exacerbations between the first and second courses of cladribine were noted in 36 patients (15.3% of all treated), almost half of the cases—those who previously received natalizumab (17 exacerbations, or 47.2% of all exacerbations between the 1st and 2nd courses of cladribine), and in 3 cases—from ocrelizumab (in 60% of all patients crossed over from ocrelizumab). During 4 years of follow-up after a full course of cladribine, exacerbations were in 14 patients (6% of all patients included in the analysis), of which in 6 cases—after crossover from natalizumab. Discussion and Conclusions: The data obtained are generally consistent with the results of meta-analyses and reviews published recently, but high probability of exacerbations in patients who were crossed over from second-line drugs such as natalizumab and ocrelizumab were seen. The crossover from natalizumab is carried out more often due to the increased risk of developing progressive multifocal encephalopathy (PML). It is likely that the restoration of MS activity after the withdrawal of natalizumab is quite frequent, cladribine tablets were not able to fully prevent this. Such a crossover does not seem to be optimal, unlike the crossover from first-line DMTs. If such a crossover is still planned, it could be performed within 4 weeks after stopping natalizumab. Full article

Background/Objectives: Crohn’s disease (CD) is a chronic immune-mediated disorder with heterogeneous response to biologic therapies. Ustekinumab (UST), an anti-IL-12/23 monoclonal antibody, is effective in CD, but predictive biomarkers of treatment response remain lacking. This study aimed to investigate cytokine dynamics during UST induction and to evaluate their association with clinical and biochemical outcomes in an observational cohort of CD patients. Methods: We prospectively recruited 31 adult patients with moderate-to-severe active CD initiating UST therapy at a tertiary referral center. Peripheral blood and stool samples were collected at baseline and weeks 4, 8, and 16. UST trough concentrations, C-reactive protein (CRP), fecal calprotectin (FC), hemoglobin, albumin, and 13 serum cytokines (including IL-1β, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-17, IL-23, TNF-α, and OSM) were analyzed. Response was defined as a ≥70% reduction in FC at week 16, or, alternatively, CRP < 5 mg/L or a Harvey–Bradshaw Index < 3. Results: Eighteen patients (58%) achieved response at week 16. Responders showed significant reductions in FC, CRP, and disease activity, while non-responders exhibited limited biochemical improvement. Overall, UST induction was associated with a global decrease in proinflammatory cytokines, particularly TNF-α and IL-1β. Responders displayed distinct cytokine patterns, with higher IL-13 levels at week 8 and lower IL-8 concentrations at week 16 compared with non-responders. UST trough levels tended to be higher in responders, and inverse correlations were observed between drug concentrations and several cytokines, including IL-6, IL-8, IL-13, and IL-23. Conclusions: UST induction leads to measurable immunological changes in CD, with differential cytokine dynamics distinguishing responders from non-responders. These findings support the potential of cytokine signatures, in combination with therapeutic drug monitoring, as pharmacodynamic biomarkers to optimize personalized treatment strategies in CD. Full article

Curcumin (Cur), a natural polyphenolic compound with potent antioxidant and anti-inflammatory properties, faces significant challenges in cosmeceutical applications due to its poor aqueous solubility and low bioavailability. Nanotechnology offers a promising approach to overcome these limitations and enhance the functionality of cosmetic formulations. In this work, Cur-loaded nanoemulsions (NEs) were developed using a droplet microfluidics technique to enhance Cur’s stability, bioavailability, and permeability for advanced cosmeceuticals. Various oils were screened for Cur solubility, with coconut oil demonstrating the highest capacity. Optimal oil-to-water flow ratios were determined to produce monodisperse NEs with controlled droplet sizes. Characterization via dynamic light scattering (DLS) revealed stable NEs with Z-potential values exceeding −30 mV at both room temperature and +4 °C for up to 21 days, indicating strong colloidal stability. Antioxidant activity was evaluated through DPPH assays, while in vitro permeability studies of the drug-loaded NEs after incorporation into suitable hydrogels, using Strat-M^® membranes mimicking human skin, demonstrated significantly enhanced penetration of the encapsulated Cur. In sum, this work highlights the potential of droplet microfluidics as a scalable and precise method for producing high-performance Cur NEs tailored for cosmeceutical applications. Full article

Resveratrol (RES), a naturally occurring polyphenolic compound with well-documented anticancer potential, is limited in clinical application due to its poor aqueous solubility and low bioavailability. This study aimed to develop RES-loaded liposomes coated sequentially with chitosan (CS) and hyaluronic acid-chitosan (HA) (RES-HA-CS-Lip) to enhance RES stability, delivery, and anticancer efficacy in breast cancer cells. HA-CS-coated liposomes were prepared using a thin-film hydration technique. Their physicochemical characteristics were thoroughly investigated through dynamic light scattering, transmission electron microscopy, Fourier transform infrared spectroscopy, and differential scanning calorimetry. The optimized RES-HA-CS-Lip exhibited spherical morphology with an average particle size of 212 nm, a narrow polydispersity index (<0.4), a zeta potential of +9.04 ± 1.0 mV, and high entrapment efficiency of 82.16%. Stability studies demonstrated superior retention of size, surface charge, and encapsulation efficiency over 28 days at both 4 °C and 25 °C. In vitro release profiles at physiological and acidic pH revealed sustained drug release, with enhanced release under acidic conditions mimicking the tumor microenvironment. Antioxidant activity, assessed via DPPH and ABTS radical-scavenging assays, indicated that RES retained its radical-scavenging potential upon encapsulation. Cytotoxicity assays demonstrated markedly improved anticancer activity against MCF-7 breast cancer cells, with an IC₅₀ of 13.08 μg/mL at 48 h, while maintaining high biocompatibility toward normal HaCaT keratinocytes. RES-HA-CS-Lip demonstrated excellent stability against degradation and aggregation. Overall, these findings highlight HA-CS-coated liposomes as a promising polysaccharide-based nanocarrier that enhances stability, bioactivity, and therapeutic efficacy of RES, representing a potential strategy for targeted breast cancer therapy. Full article

(1) Background: Pharmacist interventions are key to optimizing medication therapy and improving patient outcomes. The CLEO multidimensional tool assesses the clinical, economic, and organizational impact of these interventions, though its use in Portuguese hospital settings is limited. This study explored the predicted impact of pharmacist interventions in the Oncology Department of a Portuguese hospital, using CLEO to quantify their potential contribution to patient care and healthcare system efficiency;(2) Methods: A retrospective observational study was conducted at the hospital’s Oncology Outpatient Pharmacy between April and December 2024. Data from 144 pharmacist interventions were analyzed, focusing on drug-related problems, corrective actions, and CLEO scores. Descriptive statistics were used for data analysis; (3) Results: The most frequent drug-related problems were incorrect administration frequency (57.6%), drug interactions (22.2%), and incorrect dosing (10.4%). Nearly half of the interventions (47.2%) resulted in prescription corrections. CLEO analysis demonstrated a predicted positive clinical impact (80% of interventions scored 1C–3C), potential economic benefits (40.3% scored 1E), and organizational improvements (79.9% scored 1O), especially in lung, breast, and colorectal cancer treatments; (4) Conclusions: Pharmacist interventions were predicted to be associated with improvements in clinical, economic, and organizational outcomes in oncology care. These findings suggest that systematic documentation and evaluation of interventions using CLEO may enhance patient safety and healthcare efficiency, although further multicenter and prospective studies are needed to confirm these observations. Full article

Background/Objectives: Eosinophilic myocarditis (EM) is a rare, life-threatening inflammatory cardiomyopathy driven by eosinophil cytotoxicity and extracellular trap formation. Interleukin-5 (IL-5) inhibition may disrupt this pathogenic cascade. We reviewed contemporary evidence on IL-5 blockade in EM and contextualized it with an illustrative case. Methods: We searched PubMed through May 2025 for reports of EM treated with mepolizumab or benralizumab. Inclusion criteria were consistent with prior cohorts: acute cardiac symptoms with biomarker elevation plus abnormalities on transthoracic echocardiography and/or cardiac magnetic resonance imaging (CMR), along with documented IL-5-targeted therapy. We extracted clinical, imaging, biopsy, treatment-timing, and outcome data and included one institutional case. Results: Twenty-one episodes were analyzed (median age, 45 years; 10 men). Underlying conditions included eosinophilic granulomatosis with polyangiitis (10 cases; 48%), hypereosinophilic syndrome (5 cases; 24%), drug reaction with eosinophilia and systemic symptoms (DRESS, 3 cases; 14%), and eosinophilic asthma (3 cases; 14%). Treatments involved mepolizumab in 17 cases (81%) and benralizumab in 4 (19%); 4 patients received “early-start” therapy within 14 days of EM diagnosis. Among the 11 episodes with reported left ventricular ejection fraction (LVEF) at baseline and follow-up, the median baseline LVEF was 40% (range, 30–62), with 10 of 11 (91%) <50%. On follow-up, all 11 patients improved: 4 normalized (≥50%) and 7 improved to 40–49%. CMR (n = 18) demonstrated late gadolinium enhancement in 14 cases (78%), edema in 9 (50%), and intracardiac thrombus in 4 (22%). Endomyocardial biopsy confirmed eosinophilic infiltration in 13 of 15 cases (87%). Outcomes included one death (fulminant DRESS), one recovery following veno-arterial extracorporeal membrane oxygenation, and one successful heart transplantation. Illustrative case: A 24-year-old man on a steroid taper received mepolizumab 300 mg on Day 4. His LVEF improved from 47% to 59% by Day 15, accompanied by biomarker decline and successful steroid tapering. Conclusions: Across published cases and our institutional experience, IL-5–targeted therapy appears safe, steroid-sparing, and associated with rapid ventricular recovery, particularly when initiated early. Although limited, these findings support the need for prospective trials to define the optimal agent, dosing, timing, and integration with standard immunosuppression and anticoagulation. Full article

Background/Objectives: Cinnamon leaves, an important source of the functional compound cinnamaldehyde (CA), have been shown to be effective in improving type II diabetes and Parkinson’s disease (PD) in rats following the incorporation of cinnamon leaf extract into a nanoemulsion. However, the effect of a cinnamon leaf extract nanoemulsion (CLEN) on improving Alzheimer’s disease (AD), the most prevalent type of dementia, remains unexplored. The objectives of this study were to determine functional compounds in cinnamon leaves by UPLC-MS/MS, followed by the preparation of a nanoemulsion and its byproducts to study their effects on AD and PD in rats. Methods: Oven-dried (60 °C for 2 h) cinnamon leaf powder and hydrosol, obtained by steam distillation of cinnamon leaf powder, were stored at 4 °C. After determination of basic composition (crude protein, crude fat, carbohydrate, moisture and ash) of cinnamon leaf powder, it was extracted with 80% ethanol with sonication at 60 °C for 2 h and analyzed for bioactive compounds by UPLC-MS/MS. Then, the CLEN was prepared by mixing cinnamon leaf extract rich in CA with lecithin, soybean oil, tween 80 and ethanol in an optimal ratio, followed by evaporation to form thin-film and redissolving in deionized water. For characterization, mean particle size, polydispersity index (PDI), zeta potential, encapsulation efficiency, and surface morphology were determined. Animal experiments were done by dividing 90 male rats into 10 groups (n = 9), with groups 2–8 being subjected to mini-osmotic pump implantation surgery in brain to infuse Amyloid-beta 40 (Aβ40) solution in groups 2–8 for induction of AD, while groups 9 and 10 were pre-fed respectively with cinnamon powder in water (0.5 g/10 mL) and in hydrosol for 4 weeks, followed by induction of AD as shown above. Different treatments for a period of 4 weeks included groups 1–9, with group 1 (control) and group 2 feeding with sterilized water, while groups 3, 4 and 5 were fed respectively with high (90 mg/kg), medium (60 mg/kg) and low (30 mg/kg) doses of cinnamon leaf extracts, groups 6, 7 and 8 fed respectively with high (90 mg/kg), medium (60 mg/kg) and low (30 mg/kg) doses of nanoemulsions, groups 9 and 10 fed respectively with 10 mL/kg of cinnamon powder in water and hydrosol (0.5 g/10 mL). Morris water maze test was conducted to determine short-term memory, long-term memory and space probing of rats. After sacrificing of rats, brain and liver tissues were collected for determination of Aβ40, BACE1 and 8-oxodG in hippocampi, and AchE and malondialdehyde (MDA) in cortices, antioxidant enzymes (SOD, CAT, GSH-Px) and MDA in both cortices and livers, and dopamine in brain striata by using commercial kits. Results: The results showed that the highest level of CA (18,250.7 μg/g) was in the cinnamon leaf powder. The CLEN was prepared successfully, with an average particle size of 17.1 nm, a polydispersity index of 0.236, a zeta potential of −42.68 mV, and high stability over a 90-day storage period at 4 °C. The Morris water maze test revealed that the CLEN treatment was the most effective in improving short-term memory, long-term memory, and spatial probe test results in AD rats, followed by the cinnamon leaf extract (CLE), powder in hydrosol (PH), and powder in water (PW). Additionally, both CLEN and CLE treatments indicated a dose-dependent improvement in AD rats, while PH and PW were effective in preventing AD occurrence. Furthermore, AD occurrence accompanied by PD development was demonstrated in this study. With the exception of the induction group, declines in Aβ40, BACE1, and 8-oxodG in the hippocampi and AchE and MDA in the cortices of rats were observed for all the treatments, with the high-dose CLEN (90 mg/kg bw) exhibiting the highest efficiency. The antioxidant enzyme activity, including that of SOD, CAT, and GSH-Px, in the cortices of rats increased. In addition, dopamine content, a vital index of PD, was increased in the striata of rats, accompanied by elevations in SOD, CAT, and GSH-Px and decreased MDA in rat livers. Conclusions: These outcomes suggest that the CLEN possesses significant potential for formulation into a functional food or botanical drug for the prevention and treatment of AD and/or PD in the future. Full article

Nanogel is administered via various routes to overcome physiological barriers and achieve the desired therapeutic effect in vivo. However, developing a stable nanogel system is required to retain its therapeutic efficacy after storage. Therefore, a nanogel system composed of inorganic material (Laponite) was developed using Quality by Design (QbD) and Design of Experiments (DoE), using curcumin (CUR) as a model drug. Through a comprehensive literature review, single-factor experiments and Box–Behnken Design (BBD) experiments, we identified the CQAs and critical process parameters (CPPs), ultimately obtaining the optimal formulation. The DL, EE, Ps and PDI were determined as the CQAs and the optimal formulation was successfully prepared (LAP:CUR:TPGS = 6:2:36.6; mg;10 mL). FTIR, DSC and TEM analyses confirmed the successful loading of CUR, with a Ps in100nm, exhibiting biphasic drug release characteristics and maintaining stability for 28 days at 4 °C. QbD combined with DOE successfully facilitated stable CUR-TPGS-LAP nanogels. This study helps to better understand the critical factors in the development of nanogels and lays the foundation for the future integration of AI technology to promote a “first-time-right” drug formulation for future AI-promoted ‘one-stop’ drug formulation development model. Full article

Dry powder inhalers (DPIs) are the mainstay in the treatment of obstructive pulmonary diseases. However, the performance of DPI formulations is highly dependent on the used inhaler device and the patient’s inspiratory effort. This study aimed to evaluate and compare the aerosolization behavior of three commercially available capsule-based DPI medications—formoterol (Foradil^®), glycopyrronium (Seebri^® Breezhaler), and tiotropium (Spiriva^®)—delivered using three different capsule-based inhalers (Aerolizer, Breezhaler, and Handihaler), under varying flow conditions. Methods: The aerodynamic performance of each formulation–inhaler combination was assessed using the Next-Generation Impactor (NGI) and Dosage Unit Sampling Apparatus (DUSA) methodology. Fine particle dose (FPD) and aerodynamic particle size distribution (APSD) were determined at fixed flow rates of 15, 30, 60, and 100 L/min, as well as at inhaler-specific flow rates corresponding to a 4 kPa pressure drop. Chromatographic quantification of active ingredients was performed using validated HPLC methods specific to each drug. Results: The FPD values increased consistently with higher flow rates across all tested formulations and inhalers. At a 4 kPa pressure drop, Aerolizer and Breezhaler achieved significantly higher FPDs compared to Handihaler. Notably, in some instances, non-dedicated inhalers produced greater respirable fractions than the originally intended devices. APSD profiles revealed that drug deposition shifted toward smaller NGI stages at higher inspiratory flows, supporting enhanced deep lung delivery potential under optimal conditions. Conclusions: Device resistance, capsule orientation, and piercing mechanics substantially influence drug aerosolization. Although non-dedicated inhalers may offer improved FPDs in vitro, clinical use should adhere to approved drug–device combinations, as these have been validated for efficacy and safety under real-world conditions. Full article