Search Results (1,805)

Background/Objectives: Hepatocellular carcinoma, or liver cancer, is the sixth most common cancer worldwide and the third leading cause of cancer-related mortality. Therefore, this study aimed to develop and optimise etodolac-loaded sodium deoxycholate-stabilised shellac-based polymeric nanoparticles (ETD-SDS-SHNPs) to improve the pharmacokinetic profile of etodolac (ETD) in HepG2 human hepatocellular carcinoma (HCC) cells. Methods: The nanoprecipitation method was used to prepare ETD-SDS-SHNPs, which were then optimised using a Box–Behnken design and evaluated for particle size (PS), zeta potential (ZP), entrapment efficiency (EE), solid-state characterization, and in vitro drug dissolution. Furthermore, in vivo oral bioavailability, cytotoxicity, cellular uptake, and cell cycle progression were assessed. Results: The optimised ETD-SDS-SHNPs formulation showed an average PS of 192 ± 1.50 nm, ZP of −20.2 ± 0.4 mV, and EE of 81.6 ± 1.42%. Differential scanning calorimetry and X-ray diffraction confirmed the reduced crystallinity of ETD-SDS-SHNPs, indicating partial amorphisation of the drug in the formulation. Field-emission scanning electron microscopy revealed predominantly spherical nanoparticles with relatively smooth surfaces. The peak plasma concentration (C_max) of ETD-SDS-SHNPs (11.86 ± 0.12 µg/mL) was significantly higher than that of the pure ETD (7.15 ± 0.14 µg/mL). Similarly, the AUC_0–t for ETD-SDS-SHNPs (351.63 ± 4.59 µg·h/mL) was approximately 1.48-fold greater than that of the pure drug (236.09 ± 4.60 µg·h/mL), indicating enhanced bioavailability. ETD-SDS-SHNPs demonstrated dose-dependent enhancement of cytotoxicity against HepG2 cells, accompanied by S-phase cell cycle arrest and increased cellular uptake. Conclusions: ETD-SDS-SHNPs formulation offers an enhanced passive, efficient, and safer nanocarrier platform for repurposing etodolac in liver cancer therapy, showing significant promise for improving clinical outcomes in HCC treatment. Full article

Objectives: Fluorescence-guided surgery (FGS) targeting prostate-specific membrane antigen (PSMA) holds promise for improving surgical precision in prostate cancer. Since conjugation of fluorescent dyes to targeting vectors can substantially alter pharmacokinetic properties, we systematically evaluated a library of fluorescent dyes conjugated to a PSMA-617-derived scaffold incorporating sarcosine-based spacers to identify candidates with favorable biodistribution and optical profiles for clinical translation. Methods: Nineteen fluorescent dyes spanning NIR, large Stokes shift, and STED-compatible categories were conjugated to a dual-labeled PSMA-617-derived precursor (Glu-urea-Lys-2Nal-TXA-Sar₁₀-Lys(DOTA)-Sar₅-βAla; hereafter DP). Compounds were radiolabeled with ⁶⁸Ga or ¹⁷⁷Lu and characterized for serum stability, lipophilicity, binding affinity, and internalization in LNCaP^PSMA+ cells. In vivo pharmacokinetics were assessed in LNCaP xenograft-bearing BALB/c nu/nu mice by µPET/MRI (1 and 2 h p.i., 500 pmol ⁶⁸Ga), organ distribution (0.5, 1, and 2 h p.i., 60 pmol ¹⁷⁷Lu), and clinical-grade endoscopic fluorescence imaging. Results: All conjugates retained hydrophilic character (logD: −3.72 to −1.79), low nanomolar binding affinity (K_i: 18–87 nM), and high serum stability (94–100% intact at 24 h). Despite comparable in vitro properties, dye conjugation markedly influenced in vivo pharmacokinetics: tumor uptake at 2 h p.i. ranged from 1 to 23%ID/g and kidney accumulation from 3 to 82%ID/g. Visible-range dyes exhibited faster renal washout within the imaging window and higher tumor-to-background contrast than NIR fluorophores. Fluorescence signal intensity did not correlate with radiotracer-derived uptake, underscoring the importance of dye-specific photophysical properties. Conclusions: DP-12 (SulfoCy5), DP-15 (Alexa Fluor 647), and DP-18 (Tide Fluor 5WS) were identified as lead candidates combining favorable pharmacokinetics with strong fluorescence contrast, warranting further evaluation toward fluorescence-guided prostate cancer surgery. Full article

Olive pomace (OP), the main by-product of olive oil production, is a rich source of phenolic compounds, among which hydroxytyrosol (HT) has received considerable attention because of its biological activity. This review examines the occurrence of HT in OP and the factors that influence its formation during processing, with particular attention to the intrinsic compositional variability arising from cultivar differences, irrigation regimes, fruit maturity, and extraction systems, which collectively challenge industrial reproducibility. Current strategies for HT extraction and purification are reviewed, and the technological readiness of each method is evaluated. The biological activities of HT, particularly its antioxidant, anti-inflammatory, and cardioprotective effects, are summarized alongside a critical assessment of in vivo bioavailability data. Key research gaps are identified throughout: no pilot-scale integrated purification train has been validated, life cycle assessments comparing different recovery routes are absent, and most delivery systems lack in vivo pharmacokinetic evaluation. By bringing together studies on HT recovery and its functional properties, this review highlights the promising yet underdeveloped potential of OP as a sustainable feedstock for HT recovery and identifies the critical steps needed to advance from laboratory research to industrial application. Full article

Background: Calcium formulations are important nutritional interventions for improving insufficient calcium intake and assisting in the prevention and treatment of osteoporosis. In vitro and in vivo performance may be influenced by dosage form, calcium source, and formulation composition. In this study, an integrated approach combining in vitro dissolution, pharmacokinetic, and pharmacodynamic evaluations was used to compare the comprehensive performance of nine calcium formulations and related functional components. Methods: The nine samples were coded as CS-1 to CS-9 according to a predefined order. Calcium release characteristics were determined under simulated gastrointestinal pH conditions using a flow-through cell system. Calcium concentrations in rat plasma, feces, and urine were measured by inductively coupled plasma optical emission spectrometry (ICP-OES) to evaluate calcium exposure, excretion, and retention. Meanwhile, the bone-protective effects of different calcium preparations were assessed in a retinoic acid-induced osteoporotic ICR mouse model, and the pharmacodynamic performance of calcium citrate and various bone-derived peptide preparations was investigated in a calcium-deficient female Sprague–Dawley (SD) rat model. Results: CS-1 exhibited rapid and nearly complete calcium release in simulated gastric fluid and showed a relatively favorable dissolution profile under sequential gastrointestinal pH conditions. Calcium balance analysis indicated that calcium retention in rats was relatively higher after administration of CS-1. Animal experiments showed that different calcium sources and bone-derived peptide preparations improved bone-related parameters to varying degrees, among which CS-1 produced relatively consistent improvements in bone microarchitecture and biomechanical properties. As a functional component of the CS-1 formulation, salmon bone-derived ingredients showed activity in the comparative pharmacodynamic evaluation, suggesting that they may contribute to the overall bone-protective effect. Conclusions: Different calcium formulations showed distinct profiles in dissolution behavior, calcium retention, and bone-protective effects. Among the tested samples, CS-1 demonstrated relatively favorable overall performance, which may be related to its liquid dosage form and salmon bone-derived functional components. Full article

Imperatorin (IPT) is a naturally occurring coumarin with recognized antioxidant and anti-aging properties; unfortunately, its poor water solubility and low oral bioavailability severely limit its practical use. To get around these issues, we formulated IPT-loaded NLCs using grape seed oil and glyceryl monostearate—both food-grade excipients—with the goal of enhancing oral absorption. Optimized IPT@NLCs were prepared by high-pressure homogenization, featuring uniform spherical morphology, an average particle size of 186.63 ± 1.65 nm, a PDI of 0.188 ± 0.008, an encapsulation efficiency of 99.54 ± 0.10%, and a drug loading capacity of 9.08 ± 0.23%. IPT@NLCs remained stable in SGF, while their cumulative in vitro release over 48 h reached 90.56 ± 3.12% in SIF. We established a Caco-2/HT29-MTX-E12 co-culture monolayer to examine mucus penetration, cellular uptake, and transcellular transport routes. In parallel, oxidative stress experiments using 3T3-L1 cells, along with in vivo pharmacokinetic and gastrointestinal safety evaluations, were conducted to provide complementary evidence. Our results indicate that NLC encapsulation significantly improves both the dissolution and intestinal uptake of IPT, primarily by shifting the absorption mechanism from passive diffusion to energy-dependent active transport. In addition, IPT@NLCs effectively reduce intracellular oxidative damage through modulation of endogenous antioxidant enzyme activities. Animal studies further reveal an approximately 9-fold increase in relative oral bioavailability, with no notable irritation to gastrointestinal tissues. Overall, GSO-based NLCs offer safe and efficient oral delivery, enhancing IPT bioavailability and antioxidant activity, providing a strategy for developing natural-product-based formulations. Full article

Alzheimer’s disease (AD) is a complex neurodegenerative disorder with limited effective therapies. In this study, a series of 2-(arylamino)thiazol-4(5H)-one derivatives was synthesized using an efficient microwave-assisted protocol, and evaluated for neuroprotective effects against 6-hydroxydopamine (6-OHDA)-induced oxidative stress (OS) in SH-SY5Y neuronal cells and an Aβ42-expressing Drosophila melanogaster model of AD. Among the synthesized compounds, 3n, 3i, and 3b exhibited low cytotoxicity and significant neuroprotection, as evidenced by increased cell viability, reduced reactive oxygen species (ROS) production, and preserved mitochondrial membrane potential. Notably, compound 3n demonstrated the highest activity and effectively ameliorated Aβ42-induced behavioral deficits in vivo. Molecular docking studies predicted favorable binding affinity within the acetylcholinesterase (AChE) active site, with the thiazol scaffold and aryl substituents stabilizing ligand binding through π–π stacking and hydrophobic interactions; compound 3n also formed additional hydrogen bonds enhancing its affinity. Consistent with the docking predictions, in vitro AChE inhibition studies demonstrated that compounds 3n, 3i, and 3b inhibited AChE in a concentration-dependent manner. Network pharmacology predicted seven potential core targets implicated in AD pathogenesis and related pathways, including OS, neuroinflammation, and synaptic dysfunction. Furthermore, in silico pharmacokinetic analysis indicated compliance with Lipinski’s and Veber’s rules, supporting favorable drug-like properties. While further experimental validation is essential, these findings highlight 2-(arylamino)thiazol-4(5H)-one derivatives, particularly compound 3n, as promising multifunctional candidates for further preclinical development against AD. Full article

Background/Objectives: The chemokine receptor CXCR4 plays a pivotal role in tumor progression, metastasis, and therapy resistance and is frequently overexpressed in hematologic malignancies, including multiple myeloma and lymphoma. This study investigates a CXCR4-targeted theranostic platform comprising a PET imaging agent and two therapeutic radioconjugates derived from the high-affinity CXCR4 antagonist LY2510924. Methods: The PET tracer [¹⁸F]AlF-NOTA-SC and therapeutic radioconjugates [¹⁷⁷Lu]Lu-BL02 and [¹⁶¹Tb]Tb-BL02 were synthesized and evaluated. Radiolabeling efficiency, molar activity, and in vitro binding affinity were assessed. Specificity and uptake were evaluated in CXCR4-expressing U87.CD4.CXCR4 and MM.1S cells, with cytotoxic potential being analyzed via clonogenic survival assays. In vivo biodistribution and pharmacokinetics were evaluated in MM.1S xenograft mouse models, supported by longitudinal SPECT imaging. Results: All radioconjugates were obtained with high radiochemical purity (>98%). The constructs showed nanomolar affinity for human CXCR4; in vitro assays confirmed specific uptake in CXCR4-positive cells, and both therapeutic agents demonstrated dose-dependent cytotoxicity. In vivo, all compounds displayed comparable tumor uptake with low off-target accumulation. Co-injection studies confirmed consistent pharmacokinetics across agents, while SPECT/CT imaging demonstrated gradual tumor clearance of [¹⁷⁷Lu]Lu-BL02 over seven days. Conclusions: The radiopharmaceutical trio [¹⁸F]AlF-NOTA-SC, [¹⁷⁷Lu]Lu-BL02, and [¹⁶¹Tb]Tb-BL02 demonstrates the feasibility of a CXCR4-targeted theranostic approach for imaging and treating hematologic malignancies. The observed tumor washout highlights the need for further structural optimization to enhance tumor retention and therapeutic efficacy, providing a clear direction for future development toward clinical translation. Full article

Background/Objectives: 2-(2-Benzofuranyl)-2-imidazoline (2-BFI) is a selective imidazoline I₂-site ligand that has shown neuroprotective and neuromodulatory effects in preclinical central nervous system (CNS) studies. However, the primary preclinical literature remains fragmented across disease models, outcome types, mechanistic endpoints, and cellular targets, making it difficult to define where its therapeutic-development potential is strongest and how disease- or model-specific functional effects relate to molecular, cellular, tissue, and blood–brain barrier/neurovascular unit (BBB/NVU)-related findings. Methods: This systematic review integrated preclinical evidence from 36 original studies identified in the PubMed, Web of Science, Embase, and Scopus databases through searches last updated on May 19, 2026, to evaluate the strength of evidence for 2-BFI across CNS-related models and to connect functional, molecular, cellular, and neurovascular findings. The evidence categories included ischemic stroke/neurovascular outcomes (n = 13), traumatic CNS injury (n = 2), neuroinflammatory/neurodegeneration-related models (n = 9), behavioral pharmacology (n = 8), and cellular mechanisms (n = 4). Eligible studies were original CNS-related animal, cellular, or behavioral/pharmacological studies that directly evaluated 2-BFI and reported neuroprotective, neurological, cellular, molecular, vascular, inflammatory, neurotransmitter-related, or behavioral outcomes. Findings were synthesized qualitatively, and risk of bias in in vivo animal studies was assessed using SYRCLE’s risk-of-bias tool. Results: The most extensive preclinical evidence was found in ischemic stroke and neurovascular injury models, in which 2-BFI attenuated infarct size, neurological deficits, and edema, and suppressed apoptosis-related injury and blood–brain barrier/neurovascular unit (BBB/NVU) disruption. Across models, these effects are best interpreted as modulation of interconnected secondary injury processes involving N-methyl-D-aspartate receptor (NMDAR)/Ca²⁺-dependent excitotoxicity, oxidative and mitochondrial stress, inflammatory amplification, regulated cell death, and neurovascular destabilization. Evidence from traumatic CNS injury, autoimmune neuroinflammation, Alzheimer’s disease-related models, chronic epilepsy, and cellular stress models broadened the CNS relevance of 2-BFI but remained less replicated or more mechanistically indirect than the stroke/neurovascular evidence. Behavioral and pharmacological studies additionally indicated that 2-BFI modulates neurotransmitter-related systems associated with pain-, affective-, addiction-, opioid-, and compulsivity-related outcomes, although these findings should be distinguished from disease-modifying neuroprotective evidence. Conclusions: Meta-analysis was not conducted because of heterogeneity in models, dosing regimens, treatment timing, and outcomes. Overall, the current evidence does not yet support definitive dosing, treatment timing, or clinical development recommendations for 2-BFI. The strongest preclinical therapeutic rationale is currently found in ischemic stroke and neurovascular injury settings, whereas other CNS indications require further validation. Future studies should define dose–response relationships, therapeutic windows, pharmacokinetic and safety profiles, sex- and age-related effects, and efficacy in clinically relevant comorbid models before clinical translation is considered. The review was not prospectively registered. Funding was provided by a National Research Foundation of Korea grant funded by the Korean government. Full article

Drug delivery systems (DDS) may improve the therapeutic performance of chemotherapy in lung cancer, but their preclinical efficacy has not been quantitatively synthesized. We conducted a systematic review and meta-analysis of controlled in vivo mouse studies evaluating DDS-based chemotherapeutic formulations for lung cancer. Databases were searched from inception to 15 February 2025, and methodological quality was assessed using the SYRCLE risk-of-bias tool. Thirty studies comprising 47 experiments were included. Compared with corresponding free-drug treatments, DDS-based chemotherapy significantly reduced tumor volume (WMD −310.67 mm³; 95% CI: −375.51 to −245.83; p < 0.001), although substantial heterogeneity was observed. Both targeted and non-targeted DDS were associated with tumor growth inhibition, and targeted formulations showed a larger average reduction; however, this finding should be interpreted in light of differences in formulation properties, tumor models, and treatment protocols. Nanoparticle, liposomal, and micellar platforms all demonstrated significant antitumor effects, while combination DDS and docetaxel- or cisplatin-based systems showed large effects in subgroup analyses with variable sample sizes. These findings support the continued development of DDS-based chemotherapy for lung cancer, but standardized reporting of nanocarrier characterization, pharmacokinetics, biodistribution, toxicity, and rigorous animal-study design is required to improve reproducibility and translational relevance. Full article

Background: Assessment of antimicrobial exposure at the site of infection is essential for pharmacokinetic/pharmacodynamic (PK/PD)-guided antimicrobial therapy, yet plasma concentrations may not adequately reflect extracellular target-site exposure. This study characterized the pharmacokinetics of enrofloxacin and its active metabolite ciprofloxacin in plasma and interstitial fluid (ISF) following high-dose oral enrofloxacin administration in dogs and evaluated PK/PD target attainment using nonlinear mixed-effects (NLME) modeling and Monte Carlo simulation. Methods: Nine healthy Beagle dogs were enrolled and received a single oral dose of enrofloxacin (target dose 20 mg/kg). Following exclusion of one dog after vomiting, pharmacokinetic analyses included plasma data from eight dogs and interstitial fluid (ISF) data from six dogs. Serial plasma samples and protein-free ISF samples collected over 24 h by in vivo ultrafiltration were analyzed using LC–MS/MS. Non-compartmental and population pharmacokinetic analyses were performed separately for plasma and ISF data. Final population models were used to simulate 5000 virtual individuals for probability of target attainment (PTA) analyses across a range of minimum inhibitory concentrations (MICs) using established AUC_0–24/MIC and C_max/MIC targets. Results: Both enrofloxacin and ciprofloxacin exhibited delayed peak concentrations and greater overall exposure in ISF than in plasma. For enrofloxacin, mean AUC_0–24 was higher in ISF than in plasma (44.9 vs. 21.6 µg × h/mL). Exploratory population pharmacokinetic models adequately described the plasma and ISF concentration-time data. Monte Carlo simulations showed consistently higher PTA in ISF than in plasma. For the more conservative AUC_0–24/MIC targets (≥100 and ≥125), the MIC associated with ≥90% PTA for enrofloxacin was four-fold higher in ISF than in plasma (0.125 vs. 0.03 µg/mL). Conclusions: High-dose oral enrofloxacin produced sustained extracellular exposure, resulting in more favorable PK/PD target attainment in ISF than in plasma. These findings indicate that plasma pharmacokinetics alone may not accurately reflect target-site antimicrobial exposure and support further evaluation of ISF-based pharmacokinetic data for PK/PD-guided optimization of fluoroquinolone therapy in dogs. Full article

Background/Objectives: Given the potential for achieving high concentrations at the target site while limiting systemic exposure, delivering drugs directly to the female reproductive tract (FRT) is emerging as a promising strategy for enhancing women’s reproductive health. However, quantitative data describing matrix-specific solubility, matrix-specific binding, and permeability across FRT tissues remain limited, constraining development of physiologically based pharmacokinetic (PBPK) models for intravaginal and intrauterine therapies. Methods: Our work was conducted to help fill this critical gap, evaluating four model drugs with diverse physicochemical and transporter profiles, dapivirine (DPV), levonorgestrel (LNG), MK-2048, and 4′-ethynyl-2-fluoro-2′-deoxyadenosine (EFdA; also known as islatravir or MK-8591) in in vitro and ex vivo human models. Plasma solubility, matrix-specific binding in plasma, cervicovaginal fluid, and FRT tissues, and bidirectional permeability across FRT tissues were quantified. Results: Our results demonstrated that the plasma solubility varied markedly across compounds, following lipophilicity trends, with DPV (34.14 ± 1.04 µg/mL) and EFdA (1808.02 ± 67.36 µg/mL) exhibiting the lowest and highest solubility, respectively. Hydrophobicity-dependent solubility enhancement by plasma proteins (~2× to >30× higher comparing to aqueous solubility in the literature) was observed for all four model drugs. Apparent binding in plasma, cervicovaginal fluid, and FRT tissues was highly correlated with the model compounds’ lipophilicity, with DPV having the most highly matrix-specific binding (97–99%) and EFdA having the least matrix-specific binding with the greatest variability (15–62%). Regional permeability differed significantly across FRT tissues: the human ectocervix, myometrium, endometrium, and fallopian tubes demonstrated distinct transport patterns consistent with epithelial architecture and the transporter-substrate status of the model compounds. Efflux transporter involvement was evident for MK-2048 and EFdA in Caco-2 models (efflux ratios 2.59 and 7.14, respectively), but was less pronounced in the 3D vaginal model and ex vivo tissues. Across all datasets, permeability and binding were strongly influenced by drug lipophilicity and ionization characteristics. Conclusions: Collectively, these findings demonstrate the interplay among solubility, matrix-specific binding, and tissue permeability in governing local drug distribution within the FRT. The experimentally derived parameters provide quantitative inputs for FRT PBPK model development, and are expected to inform design of safe and effective localized therapies for women’s reproductive health. Full article

The demand for sustainable nutrients and bioactive compounds has increased interest in underutilized wild plants. Forestiera tomentosa, a Mexican drupe-bearing species, is largely unexplored. This study evaluated the proximate composition, physicochemical and functional properties, phenolic profile, antioxidant capacity, and toxicological safety of F. tomentosa fruit. The fruit showed high carbohydrate content [71.94% dry weight (DW)], with notable crude fiber (7.90% DW), protein (7.39% DW), and lipid (4.30% DW) contents. Analysis revealed a mildly acidic pH (5.66), titratable acidity of 0.32%, and total soluble solids of 2.33 °Brix. The fruit powder had a low water activity (0.42) and a favorable water solubility index (56.10%), oil absorption (4.54%), and foaming capacity (19.71%). The fruit contained high levels of soluble phenols (280.42 mg GAE/g DW), flavonoids (98.89 mg CE/g DW), anthocyanins (54.53 mg C3G/g DW), and condensed tannins (94.05 mg CE/g DW). High-performance liquid chromatography identified 20 phenolic compounds, with 3-(4-hydroxyphenyl) propionic acid, syringic acid, catechin, epicatechin, and gallocatechin being predominant. The fruit showed significant radical scavenging and reducing potential (DPPH, ABTS, and FRAP). Toxicological evaluation using the Artemia salina bioassay showed a 100% survival rate across all concentrations, indicating no acute toxicity. In silico ADMET predictions revealed favorable pharmacokinetic properties, including high intestinal absorption and compliance with Lipinski’s rule of five. These findings position F. tomentosa as a promising, non-toxic source of functional ingredients for the food, nutraceutical, and pharmaceutical industries, supporting biodiversity conservation and sustainable resource utilization. Further studies are needed to evaluate the potential health benefits of this fruit in vitro and in vivo. Full article

Toxoplasmosis remains a major global health concern, particularly in immunocompromised individuals and pregnant women, while currently available therapies are associated with significant toxicity and limited efficacy against chronic infection. Drug repurposing represents an attractive strategy for the identification of safer and more effective anti-Toxoplasma gondii agents. This study investigated the antiparasitic potential of loratadine, a second-generation antihistamine, using an integrated in silico, in vitro, and in vivo approach. The anti-T. gondii activity of loratadine was evaluated through β-galactosidase-based proliferation assays, reversibility assays, and experiments using pretreated tachyzoites. In vivo efficacy was assessed in murine models of acute and chronic toxoplasmosis. Disease progression, survival, parasite burden, and cerebral cyst formation were analyzed following treatment. Loratadine inhibited the intracellular proliferation of T. gondii tachyzoites in a concentration-dependent manner and induced partially irreversible effects on parasite viability after drug withdrawal. Pretreatment of extracellular tachyzoites produced limited effects, suggesting that loratadine predominantly acts during the intracellular stage of infection. In the acute toxoplasmosis model, loratadine treatment delayed disease progression, prolonged animal survival, and significantly reduced the number of tachyzoites recovered from the peritoneal cavity. In the chronic infection model, treatment significantly decreased both the number and size of cerebral cysts, although these findings do not demonstrate cyst eradication or direct bradyzoite killing. Despite its measurable biological activity, loratadine exhibited a relatively low in vitro selectivity index, highlighting the need for further optimization. These exploratory findings identify loratadine as a promising lead compound (hit) for further optimization rather than an immediately translatable therapeutic candidate. Additional medicinal chemistry, pharmacokinetic, mechanistic, and confirmatory preclinical studies will be required to determine its potential for anti-T. gondii drug development. Full article

Anthracycline agents, principally doxorubicin and daunorubicin, are widely used in oncology yet carry a narrow therapeutic index and pronounced interindividual pharmacokinetic variability that exposes patients simultaneously to the risk of subtherapeutic dosing and cumulative cardiotoxicity. Conventional therapeutic drug monitoring (TDM) based on periodic venous sampling and offline high-performance liquid chromatography cannot resolve the sub-minute concentration dynamics that determine organ-specific drug exposure. Electrochemical aptamer-based (EAB) sensors couple nucleic-acid aptamers, self-assembled monolayers, and methylene blue redox reporters on gold microelectrodes to convert binding-induced conformational changes into real-time, reagent-free electrochemical signals. Recent advances in this field fall into five areas: signal interrogation strategies, from kinetic differential measurement to calibration-free Fourier-transform impedance spectroscopy (FFT-EIS); interface engineering including nanostructured electrodes and AI-guided aptamer design; in vivo multi-compartment pharmacokinetic monitoring and closed-loop feedback drug delivery; the mechanisms of in vivo signal drift alongside antifouling countermeasures spanning hydrogel barriers, zwitterionic brushes, and xenonucleic acid backbone substitution; and FDA premarket pathways and clinical translation, including Premarket Approval requirements and the emerging Real-Time Clinical Trial (RTCT) framework. In live rodents, dual-compartment monitoring has resolved a reproducible 30–60 min plasma-to-ISF lag for doxorubicin at 12 s temporal resolution; calibration-free FFT-EIS interrogation achieves inter-animal coefficients of variation below 12% without individual pre-calibration; and xenonucleic acid backbone substitution has extended continuous in vivo operation to seven consecutive days. Unlike prior EAB reviews that survey general molecular targets or benchtop aptasensors, this review uniquely integrates anthracycline-specific in vivo pharmacokinetics, multi-compartment plasma–ISF monitoring, calibration-free interrogation, XNA-enabled long-term stability, and FDA/RTCT regulatory translation into a single clinical roadmap. Three gaps still separate rodent proof-of-concept work from chemotherapy patients: clinical-context validation, tumor microenvironment calibration, and anthracycline-specific XNA aptamer design. Full article

Background/Objectives: Geranylgeraniol (GGOH), an isoprenoid intermediate of the mevalonate pathway, regulates bone cell viability and function, particularly by mitigating cellular toxicity induced by nitrogen-containing bisphosphonates (N-BPs). Despite this, its role in osteoporosis remains underexplored. This scoping review synthesises evidence on the effects of GGOH in in vitro and in vivo models of osteoporosis. Methods: PubMed, Scopus, and Ovid were searched using GGOH- and osteoporosis-related terms. Primary studies evaluating GGOH exposure in cellular or animal osteoporosis models were eligible. Twenty-nine studies met the inclusion criteria. Results: In vitro findings demonstrate that GGOH reverses N-BP-induced depletion of geranylgeranyl pyrophosphate, restoring protein prenylation which is essential for osteoclast and osteoblast survival, cytoskeletal organisation, and differentiation. GGOH reduced osteoclast apoptosis, restored nuclear factor of activated T-cells 1 and carbonic anhydrase II expression, and prevented N-BP-associated suppression of bone resorption. In osteoblasts and mesenchymal stem cells, GGOH improved viability, upregulated osteogenic markers including runt-related transcription factor 2, alkaline phosphatase, collagen type I, and bone morphogenetic proteins, and rescued mineralisation impaired by alendronate or zoledronate. Independent of N-BPs, GGOH exerted divergent effects on osteoclasts, by inhibiting osteoclastogenesis or promoting retinoic acid receptor-mediated bone resorption and attenuating zoledronate protection in vascular calcification settings in a model-specific manner. In vivo, dietary GGOH supplementation improved trabecular and cortical bone parameters and reduced serum C-terminal telopeptide of type I collagen in obese mice, indicating suppression of bone resorption. Conclusions: Overall, although GGOH shows osteoprotective potential, its capacity to antagonise N-BP efficacy limits systemic co-administration. Current evidence suggests that local delivery may warrant future investigation as a strategy to mitigate N-BP-induced skeletal toxicity. However, studies evaluating bone tissue exposure, pharmacokinetics, and clinically achievable concentrations are required before this approach can be translated. Full article