Search Results (8,303)

Background: Ovarian cancer is frequently diagnosed at an advanced stage and remains one of the most lethal gynecologic malignancies. The development of multidrug resistance (MDR) during repeated chemotherapy is a major cause of treatment failure and is often associated with increased drug efflux mediated by transporters such as P-glycoprotein (P-gp). In this study, D-α-tocopheryl polyethylene glycol succinate (TPGS) and Soluplus^® (SOL) mixed micelles, abbreviated as TS, were developed to co-deliver apatinib (APA), a VEGFR-2 inhibitor, and etoposide (ETP), a topoisomerase II inhibitor, for MDR ovarian cancer models. The formulation was designed to improve the aqueous dispersion, cellular accumulation, and antitumor activity of APA and ETP. Methods: APA/ETP-loaded TS micelles (APA/ETP-mTS) were prepared and characterized in terms of particle size, polydispersity index (PDI), zeta potential, encapsulation efficiency (EE), storage stability, and in vitro drug release. Anticancer efficacy was assessed using MTT assays, cellular uptake assays, and 3D tumor spheroid studies employing HeyA8-MDR cells, followed by in vivo toxicity and antitumor efficacy studies. Micellar formulations were denoted using the cargo–carrier format, where APA/ETP indicates co-loaded APA and ETP, C6 indicates coumarin-6 (C6) used as a fluorescent probe, mTS indicates TPGS/SOL mixed micelles, and mSOL indicates SOL-only micelles. Results: The selected APA/ETP-mTS formulation showed a particle size of 20.0 ± 5.1 nm, a PDI of 0.16 ± 0.05, near-neutral zeta potential, and encapsulation efficiencies exceeding 60% for both drugs. The micelles maintained colloidal stability at 4 °C for 4 weeks, although partial decreases in encapsulation efficiency were observed. Compared with APA/ETP solution, APA/ETP-mTS delayed the release of both drugs. C6-mTS showed higher intracellular fluorescence intensity than C6-mSOL, suggesting enhanced cellular accumulation associated with TPGS incorporation. APA/ETP-mTS showed greater cytotoxicity than free drugs in HeyA8-MDR monolayer cells and produced the strongest spheroid growth inhibition among the tested micellar formulations. In the HeyA8-MDR xenograft model, APA/ETP-mTS suppressed tumor growth and resulted in the lowest final tumor weight without apparent overt toxicity based on body weight and survival observations. Conclusions: These results suggest that APA/ETP-mTS is a promising micellar co-delivery platform for hydrophobic anticancer drugs in MDR ovarian cancer. Full article

Multicomponent antibiotic–anti-inflammatory systems have recently attracted considerable attention, as this combination is becoming a standard therapy for infectious diseases. This study aimed to develop a multicomponent system comprising norfloxacin (NOR), an old fluoroquinolone antibiotic, and niflumic acid (NIF), another old, poorly soluble anti-inflammatory drug, to improve the physicochemical properties, antibiotic potency, and anti-inflammation effect, as well as their safety. First, a phase diagram was constructed to ensure solid-state reaction and to predict its stoichiometry; subsequently, the multicomponent system was prepared by solvent-drop grinding. The product was analyzed by a series of thermal analyses and powder X-ray diffraction (PXRD). Next, Fourier-transform infrared spectroscopy and nuclear magnetic resonance elucidated the molecular interactions, and the final 3D structure was determined by single-crystal X-ray diffraction, followed by Hirshfeld surface analysis. Afterward, the solubility and chemical stability were assessed using high-performance liquid chromatography, and the physical stability of the multicomponent system was evaluated by PXRD. Antimicrobial potency against Gram-negative and Gram-positive bacteria, as well as anti-inflammatory activity in vivo, were also evaluated. The results demonstrated that a newly formed antibiotic–anti-inflammatory multicomponent system, named norfloxacin–niflumate (NORNIF), in a salt dihydrate form, significantly improved the stability and antibiotic potency of NOR, including against the resistant microbe, as well as the solubility and in vivo anti-inflammatory effect of NIF simultaneously. In addition, preliminary in silico studies using Swiss-ADME and ProTox-3 predicted that the salt was well absorbed in the gastrointestinal tract and could be classified as toxicity class 4 (non-toxic). Full article

Background/Objectives: General cardio-oncology guidance describes cardiovascular toxicity from BRAF/MEK inhibitors and immune checkpoint inhibitors (ICIs), but it does not resolve how treatment decisions should change when heart failure (HF) is already present. This critical narrative review separates direct HF-specific evidence from indirect evidence and proposes an HF-centered framework for systemic melanoma. Methods: MEDLINE/PubMed, Embase, and the Cochrane Library were searched for English-language sources published from January 2015 to April 2026, with targeted guideline, prescribing-information, interaction, and geriatric-oncology updates through July 2026. Sources were classified as direct, indirect, or extrapolated. This review follows SANRA principles but does not claim systematic-review conduct, pooled estimates, formal risk-of-bias assessment, or GRADE certainty. Results: Only case-level evidence directly describes systemic melanoma treatment in established HF; most cardiotoxicity rates are derived from selected longitudinal and real-world cohorts. We therefore organize decisions across four domains: HF phenotype and current stability; oncological urgency and alternatives; treatment-specific toxicity phenotype; and detectability, reversibility, and patient priorities. Each domain is graded ordinally and generates its own decision output, and explicit precedence rules resolve situations in which several domains are simultaneously abnormal; the pathway from assessment to documented output is presented as a decision flowchart and applied to illustrative clinical cases. This approach modifies interpretation of symptoms, biomarkers, ventricular function, surveillance, drug interactions, treatment interruption, and rechallenge. Every actionable statement is labeled as guideline-supported or author-proposed, therapy-specific baseline and follow-up monitoring are tabulated separately for each treatment class, and heart failure with preserved ejection fraction is addressed as a phenotype in which clinical deterioration may occur without any change in ejection fraction. Patient-level priorities in older adults—survival, quality of life, avoidance of hospitalization, tolerance of frequent monitoring, oral versus infusion treatment, and functional expectation—are specified as items to be recorded rather than inferred. Conclusions: Stable HF is not an automatic contraindication to effective melanoma therapy, whereas recent or active decompensation requires stabilization or monitored treatment when oncological delay is unsafe. The proposed framework operationalizes guideline principles for an understudied population while making the limits of the evidence explicit. It makes a procedural rather than an empirical claim: it is a transparent structure for documenting a decision that must be made anyway, not an algorithm derived from or validated against outcome data. Full article

Liquid–liquid phase separation (LLPS), especially via coacervation, offers a novel drug delivery strategy by encapsulating therapeutic agents within phase-separated droplets, thereby improving stability, solubility, and controlled release. Polypeptides and polypeptoids are ideal biomaterials for these systems due to their versatility and tunable properties. Polypeptoids are particularly advantageous, offering enhanced enzymatic resistance and greater control over molecular interactions, making them suitable for complexation studies. This research explores the binary complexation of L-, D,L-, and N-substituted (peptoid) poly-lysine with nucleic acids, specifically two lengths of salmon sperm dsDNA and baker’s yeast tRNA, and two nucleotides, adenosine triphosphate (ATP) and cytidine triphosphate (CTP). By adjusting the charge fractions, we studied the morphology of the complexes and tested their salt resistance under different ionic conditions. Results show that dsDNA forms precipitates with lysine polypeptides and polypeptoids, whereas tRNA forms coacervate droplets, likely due to differences in secondary structure. Both nucleotides formed coacervates in all systems. L-homochiral poly-lysine complexes are the most salt-stable, followed by racemic poly-lysine, with N-substituted polymers being the least stable as ionic strength rises. For all dsDNA and tRNA systems, the complexes remained under physiologically relevant salt concentrations. These results highlight the role of salt and polymer structures in modulating complexation. The study offers insights into nucleic acid complexation, with implications for nucleic acid encapsulation and stabilization. Full article

Nickel(II) offers an appealing base for metallodrug design as it is abundant, inexpensive and forms well-defined complexes with N,O-donor ligands. Therefore, five Ni(II) complexes containing two tridentate 2-imine-8-hydroxyquinoline Schiff base ligands, derived from morpholine, piperidine, imidazole or 2-methyl-1H-limidazole, were synthesized and characterized in solution and solid state via analytical and spectroscopic techniques. Single crystals were solved using X-ray diffraction for the complex derived from 4-(2-aminopropyl)morpholine (1). This Ni(II) complex exhibits a distorted octahedrally coordinated Ni(II) center bound to two monodeprotonated NNO-tridentate ligands, adopting a meridional coordination mode, with the two oxygen atoms arranged cis to each other. The stability of the complexes in aqueous media buffered at pH 7.4 was evaluated with UV–Vis spectroscopy and their binding to bovine serum albumin (BSA) was assessed with fluorescence titrations. All complexes show strong reversible binding to BSA (K_SV ~10⁵), which stabilizes the lipophilic complexes in aqueous media. The antiproliferative activity of the complexes was screened against colon cancer cell lines (Colo205 and Colo320). They exhibit moderate anticancer activity (IC₅₀ = 15.1–92.5 μM), with structure–activity relationships favoring imidazole derivatives and maintaining activity against the doxorubicin-resistant cell line (Colo320) with resistance indices (1.3–3.1) comparable to or lower than doxorubicin. Overall, the complexes represent a platform to develop new anticancer Ni-based drugs. Full article

Background/Objectives: Etilefrine is a sympathomimetic agent increasingly used off-label as a rescue therapy for refractory neonatal chylothorax. For continuous intravenous administration in neonates, the commercially available 10 mg/mL formulation requires substantial dilution to a concentration of 4 µg/mL. However, stability data for these highly diluted preparations are currently lacking. Hence, this study aimed to assess the short-term physicochemical stability of etilefrine diluted to 4 µg/mL in 0.9% sodium chloride or 5% dextrose. Methods: Etilefrine was quantified using a high-performance liquid chromatography method coupled with ultraviolet detection. Diluted solutions were prepared in 10 mL polypropylene syringes, maintained at room temperature, and analyzed daily for 96 h. Physicochemical stability assessment included visual inspection for physical changes, assays of drug concentration, pH, osmolality, and subvisible particle counts. Results: Throughout the 96 h, no visible changes, such as precipitation, discoloration, or haze, were observed. Etilefrine concentrations in both isotonic diluents remained within 10% of the initial value. There were no significant variations in pH and osmolality. Subvisible particle counts remained below the limits established by the European Pharmacopoeia. Conclusions: Etilefrine diluted to 4 µg/mL in 0.9% sodium chloride or 5% dextrose in syringes remained physicochemically stable for 96 h at room temperature. These findings provide practical stability data to support the preparation and administration of diluted etilefrine, and may facilitate the standardization of its use in future clinical studies of refractory neonatal chylothorax. Full article

Objective: To develop a lactoferrin-modified sodium alginate nanogel loaded with saikosaponin A (SA-Lf-NG@SAA) and evaluate its potential antidepressant-like effects following intranasal administration. Methods: SA-Lf-NG@SAA nanogels were prepared and optimized using single-factor experiments combined with response surface methodology. The optimized formulation was characterized in terms of particle size, zeta potential, stability, morphology, drug-loading performance, and in vitro release behavior. Male C57BL/6J mice were used to establish a chronic unpredictable mild stress (CUMS) model to evaluate the antidepressant-like effects of SA-Lf-NG@SAA after intranasal administration. Histopathological changes in the hippocampus and striatum were observed by hematoxylin and eosin staining. Western blotting was used to detect the expression of OLFM-1, OLFM-3, and OLFM-4 in olfactory bulb tissues, and immunofluorescence staining was performed to further examine their expression in the hippocampus and striatum. Results: The optimized SA-Lf-NG@SAA nanogels had an average particle size of approximately 85 nm and a zeta potential ranging from 0 mV to −10 mV, and they maintained their basic particle characteristics during a 14-day short-term physical stability study after dispersion in PBS. In vitro release analysis showed that SA-Lf-NG@SAA exhibited a distinct initial lag phase, followed by sustained drug release, with a cumulative release rate of approximately 75% at 72 h. Kinetic fitting using zero-order, first-order, Higuchi, and Korsmeyer–Peppas models showed that the post-lag release profile was best described by the Higuchi model, suggesting a prolonged release pattern under the present in vitro conditions. In CUMS mice, intranasal administration of SA-Lf-NG@SAA effectively improved depression-like behaviors, alleviated pathological damage in the hippocampus and striatum, and enhanced neuronal morphology. Western blotting showed that SA-Lf-NG@SAA increased the expression of OLFM-1, OLFM-3, and OLFM-4 in olfactory bulb tissues. Immunofluorescence staining further confirmed that the expression of these proteins was significantly enhanced in the hippocampus and striatum, especially in the high-dose SA-Lf-NG@SAA group. Conclusions: SA-Lf-NG@SAA nanogels were successfully developed as a potential nanogel-based formulation intranasal administration of saikosaponin A, showing favorable physicochemical properties, short-term stability, and prolonged release behavior. Intranasal administration of SA-Lf-NG@SAA alleviated depression-like behaviors in CUMS mice and improved histopathological alterations in the hippocampus and striatum. The antidepressant-like effects of SA-Lf-NG@SAA may be associated with the regulation of OLFM-family protein expression in depression-related brain regions. These findings suggest that SA-Lf-NG@SAA has potential as a nanogel-based intranasal formulation for the delivery of active components from traditional Chinese medicine in depression therapy. However, the specific contribution of lactoferrin modification requires further validation using unmodified SA-NG@SAA as a control. Full article

Background/Objectives: Electron paramagnetic resonance (EPR) spectroscopy is a direct and highly specific method for detecting paramagnetic species, including free radicals, transition-metal centers, spin labels and spin probes. In pharmaceutical research, it is particularly valuable in systems involving radical chemistry, oxidative degradation, drug–membrane interactions, drug delivery carriers, metallodrugs and oxygen-sensitive microenvironments. This review aims to summarize current applications of and emerging opportunities for EPR spectroscopy in pharmaceutical research, with primary emphasis on continuous-wave (CW) EPR, the mode most widely used for routine pharmaceutical measurements. Methods: This review is organized around the main CW-EPR approaches relevant to pharmaceutical research, including direct detection of paramagnetic species, spin trapping, spin labeling and spin-probe analysis. The discussion emphasizes how spectral parameters such as the g-value, hyperfine splitting, signal intensity and linewidth can provide structural, kinetic and microenvironmental information. Results: CW-EPR supports the study of radical-mediated drug activity and toxicity, antioxidant properties, formulation stability, membrane interactions, carrier structure, metallodrug behavior and oxygenation. Its main strength is the ability to connect molecular-level radicals and paramagnetic processes with broader pharmaceutical questions related to drug efficacy, safety, stability and delivery. Conclusions: CW-EPR is a specialized but versatile analytical tool at the interface of radical chemistry, pharmaceutical technology and biomedical research. Recent developments in compact instrumentation, selective probes and spectral simulation may further expand its use in pharmaceutical development, stability assessment and drug delivery research. Full article

Background: Maintaining hemodynamic stability is crucial during coil embolization of unruptured intracranial aneurysms. Remimazolam has been suggested to exert less cardiovascular depression than propofol and may therefore provide more stable hemodynamic conditions. This study compared the hemodynamic effects of remimazolam and propofol when used for anesthesia induction and maintenance in patients undergoing coil embolization with I-gel airway management. Methods: In this single-center, randomized study, adults undergoing elective coil embolization for unruptured intracranial aneurysms were assigned to remimazolam or propofol induction followed by I-gel insertion. The primary outcome was the peak-to-nadir systolic blood pressure difference during the peri-induction period. Secondary outcomes included the peak-to-nadir mean arterial pressure difference, lowest systolic and mean arterial pressures, the incidence of hypotension, vasoactive drug requirements, and recovery outcomes. Results: Of the 50 patients randomized, 46 were included in the analysis, including 22 in the remimazolam group and 24 in the propofol group. The peri-induction peak-to-nadir systolic blood pressure difference was smaller with remimazolam than with propofol (38.2 ± 13.2 vs. 51.7 ± 13.4 mmHg, p = 0.001). The peak-to-nadir mean arterial pressure difference was also smaller, while the lowest systolic and mean arterial pressures were higher, with remimazolam. The incidence of hypotension was lower with remimazolam (40.9% vs. 87.5%, p = 0.002), with correspondingly lower requirements for ephedrine and norepinephrine. Conclusions: Remimazolam-based anesthesia was associated with a smaller peri-induction peak-to-nadir systolic blood pressure difference, a lower incidence of hypotension, and less frequent vasoactive drug use than propofol during I-gel-facilitated anesthesia for unruptured intracranial aneurysm coil embolization. These findings suggest a favorable hemodynamic profile in this setting and support further evaluation in larger trials. Full article

Resveratrol remains one of the most extensively studied plant-derived polyphenols because of its broad antioxidant, anti-inflammatory, cardioprotective, neuroprotective, and anticancer activities. However, its clinical translation has been substantially limited by its poor aqueous solubility, rapid phase II metabolism, and low systemic bioavailability, despite decades of intensive investigation. Structural modification through methoxylation has emerged as a promising strategy to overcome these pharmacokinetic limitations by enhancing metabolic stability, lipophilicity, membrane permeability, and biological activity. While considerable attention has focused on resveratrol and a limited number of established analogs, emerging methoxylated derivatives remain comparatively underexplored. This review highlights the structural characteristics, biological activities, and molecular mechanisms of two such derivatives, 4,4-(ethane-1,2-diyl)bis(2-methoxyphenol) (EG) and (Z)-3,5,4′-trimethoxystilbene (Z-TMS), and discusses evidence from structurally similar, better-characterized compounds that may aid in understanding their activities. Despite promising experimental findings, the therapeutic relevance of EG and Z-TMS remains insufficiently characterized because the available evidence is predominantly derived from in vitro studies, while data on toxicity, therapeutic index, long-term safety, pharmacodynamics, and clinically relevant systemic exposure remain limited. This review emphasizes the anticancer potential of these emerging methoxylated derivatives, identifies current knowledge gaps, and provides a basis for considering them as lead compounds for anticancer drug development. Full article

Inflammation is a complex biological response involved in the pathophysiology of several chronic diseases. Although conventional anti-inflammatory therapies are effective, their prolonged use can be associated with relevant adverse effects. Although non-steroidal anti-inflammatory drugs and glucocorticoids are widely used, these agents cause gastrointestinal, renal, cardiovascular, hepatic and metabolic adverse effects. Essential oils (EO) exhibit relevant anti-inflammatory potential. However, their pharmaceutical application is limited by volatility, hydrophobicity, physicochemical instability and potentially low bioavailability. This review evaluated EO-loaded lipid nanocarriers for anti-inflammatory applications, with emphasis on physicochemical quality attributes, stability, safety and efficacy. Literature searches were carried out through PubMed/MEDLINE, PubMed Central, ScienceDirect, SciELO, Virtual Health Library, and Google Scholar websites, based on works published between 2021 and 2026. The investigated systems included liposomes, solid lipid nanoparticles, nanostructured lipid carriers and nanoemulsions. Different formulations were found regarding EO nature, nanocarrier type, administration route and biological models used, predominantly involving preclinical assays. Nanoencapsulation was frequently associated with suitable physicochemical properties and release profiles, but direct comparisons with the corresponding free EO and control nanocarriers were not consistently performed. Safety findings were mainly based on cytotoxicity, local tolerability and short-term assays, with limited repeated-dose and long-term toxicological data. Several formulations showed anti-inflammatory activity in acute, subacute, or chronic experimental models. In selected works using the same experimental conditions, some formulations produced responses of similar magnitude to hydrocortisone, diclofenac, or other anti-inflammatory drugs, but these results cannot be directly correlated with therapeutic equivalence. The reported mechanisms involved modulation of the NF-κB, MAPK and Keap1/Nrf2/HO-1 signaling pathways. Overall, lipid-based nanocarriers represent platforms for investigating the stability, delivery and biological performance of EO. However, further standardization and controlled assays are required to determine their therapeutic and translational potential. Full article

Background/Objectives: Diabetic foot ulcers are characterized by persistent inflammation, impaired angiogenesis, and delayed tissue regeneration. Epidermal growth factor (EGF) is an important regulator of wound repair; however, its therapeutic application may be limited by rapid degradation and poor retention within the wound environment. This study investigated the therapeutic efficacy of local administration of EGF and ceftriaxone using autologous red blood cell-derived carriers (RBCDCs) in an experimental model of diabetic wound healing in rats. Methods: Experiments were conducted on 30 albino Wistar rats (250 ± 20 g) with experimentally induced diabetic wounds. In the RBCDC treatment groups, separately prepared drug-loaded RBCDC formulations containing EGF or ceftriaxone were locally administered into the wound. The corresponding comparison groups received the same active agents in free form according to an identical treatment schedule, while an additional control group received topical Levomekol. Results: RBCDC-mediated administration of EGF and ceftriaxone significantly accelerated wound closure and was associated with earlier resolution of inflammation, granulation tissue maturation, re-epithelialization, collagen deposition, and angiogenesis compared with the corresponding free-drug formulations. On day 9, tissue EGF concentration was higher in the RBCDC (EGF + Ctx) group than in the corresponding free-drug group. Additional formulation characterization demonstrated ceftriaxone encapsulation and in vitro release from RBCDCs, as well as in vitro EGF release from EGF-loaded RBCDCs. Conclusions: Autologous RBCDCs represent a promising local drug-carrier platform for the administration of regenerative and antimicrobial agents in experimental diabetic wounds. Further studies are required to establish local pharmacokinetics, systemic exposure, carrier stability, and the mechanisms responsible for the observed therapeutic effects. Full article

Breast cancer remains one of the leading causes of global mortality, which has growing driving interest in dietary natural products for potential chemopreventive and complementary approaches. Cherries (Prunus species) are rich in bioactive phytochemicals, notably anthocyanins, hydroxycinnamic acids, and the flavonols quercetin and kaempferol. This review aims to examine and discuss current research on the molecular targets and mechanisms of action of whole cherry extracts and their primary flavonols quercetin and kaempferol across various breast cancer subtypes. Preclinical studies indicate that these compounds exert multi-targeted effects by inducing apoptosis, inhibiting cell proliferation, and suppressing metastatic pathways. Additionally, these flavonols show potential in reversing multidrug resistance. A whole-food approach highlights the candidate synergistic properties of these phytochemical complexes, but low oral bioavailability and rapid metabolism severely limit their clinical translation. Therefore, utilizing innovative drug delivery systems remains crucial to improving their stability, absorption, and overall therapeutic efficacy. Full article

Monoclonal antibody-based therapies are widely used in chronic immune-mediated diseases, but their periodontal effects, dentoalveolar safety signals, and exposure characteristics remain incompletely characterized. This scoping review mapped periodontal clinical outcomes, biomarkers, microbiological and imaging findings, dentoalveolar safety, administration, treatment exposure, and pharmaceutical-context reporting. PubMed, Scopus, and Web of Science were searched in July 2026 without publication-year or language restrictions. Twenty-one reports representing 20 studies or cohort families were included. Evidence mainly concerned rheumatoid arthritis and therapies targeting tumor necrosis factor, interleukin-6 receptor, and cluster of differentiation 20. Evidence for interleukin-17A inhibition was insufficient and derived from one confounded five-patient case series. Tocilizumab showed the most consistent reductions in gingival inflammation and bleeding on probing, while structural changes were smaller and inconsistent. Tumor necrosis factor-directed findings were heterogeneous. Small rituximab studies showed favorable clinical or biomarker signals, whereas pharmacovigilance identified infectious and destructive dentoalveolar signals. Exposure reporting was incomplete, and no included periodontal study evaluated formulation stability, storage, cold-chain integrity, or handling deviations. This review integrates treatment-effect evidence, safety signals, and exposure variables across antibody targets and identifies a pharmaceutical–periodontal reporting gap requiring prospective investigation. Full article

Polymeric drug carriers have emerged as versatile platforms for improving therapeutic efficacy, drug stability and controlled and sustained release of active pharmaceutical ingredients. Conventional manufacturing techniques often rely on high processing temperatures, utilization of organic solvents and consequent purification procedures that may compromise morphology, encapsulation efficiency and carrier biocompatibility. Supercritical fluid technologies overcome the limitations of conventional methods and emerge as environmentally friendly, sustainable and flexible alternatives to produce advanced polymeric drug carriers. This review provides insights into the most widespread supercritical fluid technologies, encompassing the most recent advancements (2022–2026) made in the field of porous materials, micro- and nanoparticles and microcapsules. Emphasis was placed on carrier characteristics, features and applicative translation; this review aims at evidencing advantages, current limitations and future perspectives of supercritical fluid technologies, aiming at encouraging technological and industrial advancement of next-generation advanced polymeric drug carriers. Full article