Search Results (2,540)

Cancer progression is closely associated with dysregulation of apoptosis, enabling malignant cells to evade programmed cell death and develop resistance to therapy. Among the key regulators of this process, the tumor suppressor protein p53 and the Bcl-2 family of proteins play central and interconnected roles in controlling cell survival and mitochondrial integrity. In recent years, naturally occurring flavonoids have attracted considerable attention as potential modulators of these pathways due to their diverse biological activities and relatively low toxicity. This review provides a focused and integrative overview of how different subclasses of flavonoids modulate the p53–Bcl-2 signaling axis to regulate apoptosis in cancer cells. Particular emphasis is placed on the mechanistic interplay between p53 stabilization, transcriptional regulation of apoptotic targets, mitochondrial outer membrane permeabilization, and caspase activation. In contrast to previous general reviews on flavonoids and cancer, this work provides an integrated overview of evidence across multiple flavonoid subclasses and experimental cancer models, highlighting both shared and pathway-specific apoptotic responses. Experimental findings from in vitro and in vivo studies are discussed, including the effects of quercetin, kaempferol, myricetin, epigallocatechin gallate, and related compounds on cell-cycle arrest, oxidative stress, mitochondrial dysfunction, and intrinsic apoptotic signaling. Furthermore, the review examines the relationship between flavonoid chemical structure and biological activity, with particular attention to bioavailability, metabolic transformation, and strategies aimed at improving therapeutic efficacy, including structural modification and nanocarrier-based delivery systems. Despite promising preclinical findings, significant translational challenges remain, including poor pharmacokinetic properties, variability among experimental models, and limited clinical validation. Overall, flavonoids represent a promising class of bioactive compounds capable of targeting apoptosis through modulation of the p53–Bcl-2 network, and a deeper mechanistic understanding of their activity may support the development of novel targeted and combination anticancer therapies. Full article

Background/Objectives: Cyclotides are plant-derived macrocyclic peptides distinguished by their head-to-tail cyclized backbone and cystine knot motif, which confer remarkable stability against thermal, enzymatic, and chemical degradation. These features, combined with a compact and rigid structure, position cyclotides as promising scaffolds for future antibacterial agents in response to the escalating threat of multidrug-resistant (MDR) pathogens and the stagnation of conventional antibiotic discovery pipelines. This review summarizes the structural features, antibacterial mechanisms, bioengineering strategies, and translational potential of cyclotides against MDR infections. Methods: A narrative review of the literature was conducted using recent original research articles and reviews on cyclotide structure, antibacterial activity, bioengineering, computational modeling, and pharmaceutical applications. Results: Cyclotides exhibit potent antimicrobial activity, primarily through membrane disruption mediated by amphipathic surfaces and affinity for anionic bacterial membranes. Some variants also demonstrate anti-virulence and antibiofilm properties, broadening their therapeutic relevance for difficult-to-treat infections. Bioengineering approaches, including epitope grafting and rational design, have improved selectivity and potency while reducing cytotoxicity. Advances in computational modeling, molecular dynamics, and artificial intelligence have accelerated the prediction and optimization of antimicrobial activity, toxicity, and pharmacokinetic properties. Conclusions: Innovations in synthesis, including recombinant expression and enzymatic ligation, are helping overcome translational barriers related to cost and scalability. Although challenges remain in oral bioavailability and systemic delivery, strategies such as lipidation and scaffold modification support the development of cyclotide-based therapeutics as adaptable platforms for peptide drug discovery. Full article

The pharmacokinetics (PK) and pharmacokinetic–pharmacodynamic (PK/PD) relationships of cefquinome in small ruminants remain incompletely characterized, particularly for long-acting (LA) formulations. This study evaluated cefquinome disposition after intravenous (IV), subcutaneous (SC) and LA subcutaneous (SC-LA) administration in lactating sheep and goats using nonlinear mixed-effects models (NLMEs) and Monte Carlo (MC) simulations. Cefquinome exhibited low volumes of distribution (0.21–0.31 L/kg), with goats showing higher clearance and shorter terminal half-lives than sheep. The SC-LA formulation reduced the absorption rate constant and increased both the mean absorption time and terminal half-life by 4–6-fold, resulting in sustained systemic exposure over 48 h. PK/PD analysis showed higher PK/PD cut-off values for the LA formulation, with values of 0.125 μg/mL for the fT > MIC index and 0.25 μg/mL for the fAUC/MIC index, respectively, whereas IV and SC regimens achieved lower thresholds. MC simulations indicated that only the LA formulation achieved ≥ 90% probability of target attainment (PTA) values at MICs equivalent to tentative epidemiological cut-off values (TECOFF) for respiratory pathogens. Notably, fAUC/MIC provided a more informative descriptor of efficacy for the LA formulation. These findings highlight the advantage of LA formulations and demonstrate improved performance compared with conventional dosing regimens in sheep and goats. Full article

Scorpion venom peptides, with their stable disulfide backbone, compact structural framework, and highly selective regulation of ion channels, have long been regarded as important molecular probes in neuropharmacology. However, recent studies have revealed their potential for regulating oxidative stress, inflammation, and neuroprotection, making them a new research frontier. In this article, we focus on scorpion venom peptides as drugs, constructing an integrated knowledge framework from structural classification to clinical translation. First, scorpion venom peptides are systematically classified based on cysteine arrangement patterns and three-dimensional folding topology, and their structure–activity relationships are summarized. Based on this, the molecular mechanisms by which scorpion venom peptides regulate ion channels are systematically analyzed. We review the emerging pharmacological activities of scorpion venom peptides. Of particular note, the representative molecule SVHRSP has shown multi-target synergistic antioxidant and neuroprotective activity in models of Parkinson’s disease. We also systematically evaluate the application of engineering strategies, including cyclisation modification, nanodelivery, recombinant expression, and AI-assisted optimization, to overcome the translational bottlenecks in the development of scorpion venom peptides. However, it should be noted that most SVHRSP-related findings have been reported by a single research group; independent replication, pharmacokinetic characterization, and human efficacy data are still lacking. Its IND approval permits clinical investigation but does not yet constitute proven therapeutic benefit in patients. By integrating molecular structure, redox regulation mechanisms, and translational medicine perspectives, this review aims at providing a theoretical basis and practical pathways for scorpion venom peptides as precision therapeutic molecules for oxidative stress-related diseases. Full article

Marburg virus (MARV), a highly pathogenic member of the Filoviridae family, causes severe hemorrhagic fever with a high case fatality rate and currently lacks effective therapeutics. The viral entry process, mediated by the interaction between the MARV glycoprotein (GP) and host receptor C-type lectin domain family 4 member M (CLEC4M) (L-SIGN), represents a critical target for early-stage intervention. The active compounds from BindingDB and the decoy from DUDE were used. The RDKit was used for feature engineering. Machine learning models were trained on an initial dataset consisting of 56 active chemicals and 1232 decoys. Among the tested algorithms, the Random Forest model demonstrated superior performance, achieving the highest discriminative ability (AUC = 0.93, MCC = 0.88) on the test set. Virtual screening of 11,032 phytochemicals resulted in 120 predicted actives, of which 42 compounds satisfied drug-likeness criteria. Subsequent molecular docking identified three lead compounds (PubChem IDs: 42608095, 5281601, and 11243993) with moderate-to-promising binding affinities (−6.3 to −6.5 kcal/mol) toward the CLEC4M binding site. ADMET analysis revealed favorable pharmacokinetic and toxicity profiles for the selected lead compounds. DFT calculations of the three compounds highlighted their electronic stability and reactive nature, indicating that PubChem IDs 42608095 and 5281601 possess particularly stable electronic properties conducive to favorable target interactions. Combining machine learning models with molecular docking and Molecular Dynamics (MD) simulations worked well in finding promising phytochemical inhibitors. The MM/GBSA binding free energy calculations further confirmed binding affinities, with values of −10.83 and −11.08 kcal/mol, respectively, suggesting favorable complex stability. These findings provide a pathway for developing new antiviral agents against MARV, pending further experimental validation and optimization. Full article

Background: Dental caries is a chronic disease mediated by biofilm, which is caused by Streptococcus mutans, and enamel genetics modulates susceptibility. The variants of ENAM might alter the adhesion of enamel and bacteria. One important anti-viral target is sortase A (SrtA), which restricts colonization but does not have an impact on bacterial survival. Aim: The aim of this study was to find out the relationship between ENAM rs3796704 and dental caries vulnerability among adult Iraqi Arab females and to assess the antibiofilm capacity of eugenol and cinnamic acid against S. mutans SrtA using molecular docking, ADMET prediction, and molecular dynamics modeling. Methods: A case–control study was done on 240 women (aged 25–30 years; 120 caries, 120 controls). HRM real-time PCR was done to genotype ENAM rs3796704. An analysis of allelic and genotypic distributions was done using chi-square tests and odds ratios (p < 0.05). An in silico docking analysis aimed at SrtA (PDB: 4TQX) was performed in AutoDock Vina, and this was followed by ADMET profiling and a 50 ns molecular dynamics simulation (OPLS4/TIP3P, NPT 300 K/1 atm). Results: The level of the G allele was found to be lower in the cases than in the controls (60% vs. 70; OR = 0.6429; p = 0.02), but the level of the A allele was found to be higher in the cases (40% vs. 30; OR = 1.5556; p = 0.02). Docking showed a minor difference in binding affinities with eugenol (−4.961 kcal/mol) and cinnamic acid (−4.939 kcal/mol) as compared with chlorhexidine (−4.692 kcal/mol). Both compounds showed stable binding for more than 50 ns as well as desirable predicted pharmacokinetics. Conclusions: The caries vulnerability in this sample was associated with ENAM rs3796704. Eugenol and cinnamic acid undergo stable dissociative interactions with SrtA and were found to have favorable safety profiles in silico. Therefore, they may be considered as adjunctive anti-virulence agents in the prevention of caries. Full article

In this study, we assessed the impact of repeated valproate administration on its anticonvulsant effects and side effects in mice. We measured the plasma and brain concentrations of valproate and examined changes in the expression of selected genes in the mouse hippocampus after both acute and chronic treatments. Electroconvulsions were induced using an alternating current (50 Hz, 25 mA, 0.2 s) through ear clip electrodes. Motor impairment and long-term memory deficits were assessed with the chimney test and passive avoidance task. Valproate concentrations in the brain and plasma were measured by a fluorescence polarization immunoassay. mRNA was isolated using a modified Chomczyński and Sacchi method, and RQ-PCR was performed with an Applied Biosystems 7900 using SDS and RQ Study software. The 50% effective dose (ED₅₀) of valproate in the 14 × 2 protocol was significantly lower than the control. Despite no observed memory deficits in chronic protocols, the 50% toxic dose (TD₅₀) for motor impairment was also significantly lower. Chronic valproate treatment did not alter the plasma and brain concentrations. However, the expression levels of three genes (CACNA1G, GAD1, SCN1A) were significantly higher in the chronic protocols with the higher dose of valproate compared to single protocols, suggesting a dose-dependent effect. The repeated administration of valproate resulted in both enhanced efficacy and increased toxicity in terms of motor impairment. The observed effect may be associated with transcriptional adaptations potentially mediated by epigenetic mechanisms rather than with pharmacokinetic events. To enhance the reliability of the results obtained in animal epilepsy models, antiepileptic drugs should be administered chronically. Full article

Background/Objectives: Zastaprazan (JP-1366) is a novel potassium-competitive acid blocker (P-CAB) used for the treatment of gastroesophageal reflux disease (GERD). To date, its metabolic pathways and metabolism-related drug–drug interactions (DDIs) in humans remain incompletely elucidated. This study aimed to determine the relative contributions (f_m) of cytochrome P450 isoforms to JP-1366 elimination and assess its DDI potential. Methods/Results: In vitro metabolic studies using human liver microsomes (HLMs) revealed that JP-1366 was first metabolized to M1, which subsequently underwent further oxidation, glucuronidation, and N-dealkylation. Mono-oxidation was estimated to contribute more than 46% to the overall metabolic clearance of JP-1366. Reaction phenotyping identified CYP3A as the major enzyme (f_m = 96.1%), followed by CYP1A2 (1.49%) and CYP2C9 (2.41%). By integrating in vitro data, clinical pharmacokinetic data and clarithromycin coadministration DDI data, a physiologically based pharmacokinetic (PBPK) model was developed and validated. Simulations predicted significant DDIs with strong CYP3A inhibitor (ketoconazole), with AUC ratios of 3.80. Moderate inhibitors (fluconazole and fluvoxamine) caused mild increases (AUC ratios: 1.14–1.74). Conversely, strong and moderate CYP3A inducers, rifampicin and efavirenz, produced pronounced DDIs, with AUC ratios of 0.22 and 0.50, respectively. Furthermore, simulations predicted that although JP-1366 functions as a CYP enzyme inhibitor, it would not cause clinically meaningful changes in the plasma exposure of corresponding CYP substrate drugs; however, potential interactions with CYP3A substrates still warranted consideration. Conclusions: JP-1366 is predominantly cleared via a CYP3A-dominated metabolic pathway. The PBPK simulations suggest that JP-1366 may be a moderately sensitive CYP3A substrate and a moderate inhibitor of sensitive CYP3A substrates, while its perpetrator DDI risk toward other major CYP pathways appears limited. These findings support caution or monitoring when JP-1366 is co-administered with strong CYP3A modulators or sensitive CYP3A substrates. Full article

Carbapenem-resistant Enterobacterales (CRE) are a major therapeutic challenge because of limited treatment options and high mortality. Despite advances in resistance-targeted therapies and pharmacokinetic (PK) optimization, treatment failure remains common. This review examines how resistance mechanisms and antibiotic exposure at the infection site jointly influence therapeutic outcomes in CRE infections. A mechanistic synthesis of evidence on carbapenem PKs, bacterial resistance, and nanoparticle (NP)-based delivery systems was performed. Based on this analysis, we propose the Pre-Target Interception Model (PTIM), which describes treatment failure as the progressive loss of active antibiotic before reaching penicillin-binding proteins. Unlike conventional approaches that focus primarily on resistance determinants or drug delivery platforms, PTIM emphasizes the factors that limit effective antibiotic exposure within infected tissues. Within this framework, nanocarrier systems are assessed according to their ability to protect antibiotics, enhance tissue penetration, and improve retention under conditions of enzymatic degradation, membrane restriction, efflux activity, and biofilm-associated diffusion barriers. However, clinical translation remains limited by manufacturing challenges, variability in NP performance, and the lack of validation in CRE-specific settings. Future progress will require quantitative measurement of antibiotic exposure at infection sites, standardized evaluation of nanocarrier performance, and validation in clinically relevant models. PTIM provides a framework for the rational development of nanomedicines designed to improve antibiotic delivery in CRE infections. Full article

Alzheimer’s disease (AD) is a complex neurodegenerative disorder with features of amyloid-beta (Aβ) accumulations, tau hyperphosphorylation, oxidative stress, neuroinflammation, and synaptic losses. Despite extensive therapeutic investigations for many decades, the clinical treatment options remained largely symptomatic, while anti-amyloid antibody therapies were expensive and had limited accessibility. A subclass of triterpenoids generated from plants, pentacyclic triterpenic acids (PTAs), exhibited a variety of pharmacological properties. The neuroprotective effects of some important PTAs in AD models were reviewed in this study. These phytochemicals displayed a multimodal neuroprotection by lowering amyloid and tau, improving mitochondrial function, inhibiting inflammation, and improving synaptic plasticity and cognition. However, the neuroprotective mechanisms of several PTAs remained poorly characterized. In addition, most evidence were preclinical, while poor bioavailability and the limited clinical validation hindered the therapeutic translation. Studies were needed to evaluate these phytochemicals in AD, improve their pharmacokinetics, and enhance brain delivery. Their diverse bioactivities and encouraging preclinical findings suggest these compounds may serve as promising lead candidates for future drug development in neurodegenerative diseases. Full article

Background/Objectives: Aztreonam/avibactam is a promising treatment option for serious infections caused by metallo-β-lactamase-producing carbapenem-resistant Enterobacterales (MBL-CRE). However, the labeled regimen is operationally demanding because it requires frequent, prolonged infusions, and the recommended loading dose does not match the commercially available vial strength. This population pharmacokinetic (PopPK)-based Monte Carlo simulation study aimed to optimize aztreonam/avibactam dosing across renal function strata while maintaining pharmacokinetic/pharmacodynamic (PK/PD) target attainment. Methods: Published PopPK models for aztreonam and avibactam were reconstructed and applied in Monte Carlo simulations. Virtual adult patients (body weight 70 kg) were stratified into five renal function groups according to creatinine clearance (CrCL): 101–120, 81–100, 51–80, 31–50, and 15–30 mL/min. Simulated scenarios varied infusion duration, dosing interval, maintenance dose, and loading strategy. Prespecified PK/PD targets were 60% fT > MIC (the percentage of dosing interval that free drug concentration remains above the minimum inhibitory concentration) for aztreonam (MIC 8 mg/L) and 50% fT > CT (the percentage of dosing interval that free drug concentration remains above the critical threshold concentration) for avibactam (CT 2.5 mg/L). A joint probability of target attainment (PTA) ≥ 90% was considered acceptable. Results: Regimen performance differed across renal function strata. For patients with CrCL > 80 mL/min, the labeled q6h regimen infused over 3 h remained the most robust option, whereas shortening the infusion to 1 h or 2 h reduced target attainment. In the CrCL 51–80 and 31–50 mL/min subgroups, both q6h/3 h and q6h/2 h regimens generally achieved acceptable PTA. However, in the CrCL 31–50 mL/min subgroup receiving q6h/2 h administration, omitting a loading dose was associated with reduced early avibactam exposure. In the CrCL 15–30 mL/min subgroup, a simplified half-vial regimen (0.75/0.25 g q8h/2 h) provided PTA comparable to that of the complex labeled reduced-dose regimen. Across loading dose scenarios, omission of the loading dose was best supported in the CrCL 51–80 mL/min subgroup, whereas retaining the labeled loading dose remained the more prudent approach in the CrCL 31–50 mL/min subgroup when a 2 h infusion was used. Conclusions: PopPK-guided, renal function-stratified simplification of aztreonam/avibactam dosing may improve clinical practicality without materially compromising PK/PD target attainment in selected patient subgroups. A 2 h infusion appears a reasonable alternative for patients with CrCL 31–80 mL/min, and a 0.75/0.25 g q8h/2 h half-vial regimen may be considered a plausible exploratory option for patients with CrCL 15–30 mL/min. These findings support more feasible administration strategies, but prospective clinical validation remains necessary. Full article

Background: Cenobamate is a novel antiseizure medication with potential interactions involving cytochrome P450 enzymes, including CYP2C19. Genetic variability in CYP2C19 may influence drug metabolism and tolerability, although its clinical relevance in cenobamate-treated patients remains unclear. Methods: We conducted a single-center retrospective study including 48 adults with drug-resistant epilepsy treated with cenobamate. Patients were stratified by concomitant use of CYP2C19-substrate ASMs (patients with CYP2C19 substrates vs. patients without CYP2C19 substrates). CYP2C19 genotype was classified into metabolizer phenotypes. Adverse events (AEs) were categorized as potentially CYP-mediated or likely unrelated to CYP-mediated pharmacokinetic mechanisms based on clinical assessment, temporal association, and known pharmacological interaction profiles. Associations were explored using descriptive statistics and regression models. Results: Overall, 58.3% of patients received CYP2C19-substrate ASMs. AEs were more frequent among patients with CYP2C19 substrates (71.4% vs. 20.0%; p = 0.001), with potentially CYP-mediated AEs observed only in this group (32.1% vs. 0%; p < 0.001). Intermediate metabolizers showed a higher proportion of potentially CYP-mediated AEs (87.5%; p < 0.001). This pattern was not observed in patients without CYP2C19 substrates. Regression analyses suggested increased risk in intermediate metabolizers, although estimates were imprecise and should be considered exploratory. Conclusions: An exploratory association between CYP2C19 variability and AE occurrence was observed in patients treated with cenobamate combined mainly with clobazam and other CYP2C19-substrate ASMs. Intermediate metabolizers may represent a higher-risk subgroup, but these preliminary findings require prospective confirmation with pharmacokinetic monitoring. Full article

Radiotherapy remains a central component of standard treatment for glioblastoma (GBM), yet recurrence is common because GBM radioresistance is reinforced by enhanced DNA damage repair, glioma stem cells (GSCs), hypoxia, extracellular matrix remodeling, and an immunosuppressive tumor microenvironment. FLASH radiotherapy (FLASH-RT), delivered at ultra-high dose rates, has shown reproducible normal-tissue-sparing effects in preclinical models, including the brain. In GBM models, however, available evidence indicates that FLASH-RT generally preserves tumor control at levels comparable to conventional radiotherapy rather than providing clearly superior eradication of hypoxic or stem-like tumor compartments. In parallel, endoplasmic reticulum (ER)-targeted interventions have emerged as a candidate strategy for disturbing tumor proteostasis, modulating unfolded protein response (UPR) signaling, impairing synthesis of repair-associated proteins, and promoting immunogenic cell death. This narrative review summarizes representative mechanisms of GBM radioresistance, appraises the opportunities and limitations of FLASH-RT in intracranial disease, and explains why ER targeting is discussed here as a lead but unproven biological axis for radiosensitization. We further compare ER-directed approaches with mitochondrial-, lysosomal-, and delivery-enabled radiosensitization strategies, and outline the translational variables that would determine clinical testability, including beam modality, blood–brain barrier heterogeneity, pharmacokinetics, treatment sequencing, and biomarker development. In this review, “physical precision” refers primarily to dose-rate-driven ultra-rapid delivery and the possibility of widening the normal-tissue therapeutic window under FLASH conditions, rather than to a universal depth–dose advantage shared by all FLASH platforms. Direct experimental evidence for combining FLASH-RT with ER-targeted therapy in GBM is currently lacking. We therefore present this model as a hypothesis-generating conceptual and translational framework for future preclinical testing rather than as an established therapeutic advance. Full article

Background: Resveratrol is a plant-derived polyphenol with reported anti-inflammatory activity, and the MCP-1/CCL2 axis is a key mediator of monocyte recruitment and inflammatory tissue remodeling. Although individual preclinical studies have examined resveratrol effects on MCP-1/CCL2-related outcomes, the overall in vivo evidence has not been quantitatively synthesized. This systematic review and meta-analysis evaluated whether resveratrol treatment is associated with reduced MCP-1/CCL2-related inflammatory readouts in animal models. Methods: The protocol was registered in PROSPERO (CRD420261339126), and reporting followed the PRISMA 2020 statement. PubMed was searched from inception to 12 March 2026, with additional reference-list screening. Eligible studies were in vivo animal experiments comparing resveratrol-treated and control groups with extractable quantitative MCP-1/CCL2-related outcomes. Effect sizes were calculated as Hedges’ g with 95% confidence intervals and pooled using random-effects models fitted by restricted maximum likelihood. Subgroup, sensitivity, cumulative, influence, funnel-plot, dose meta-regression, and SYRCLE-based risk-of-bias analyses were conducted. Results: Twenty-seven studies contributing 29 analyzable datasets were included. The overall pooled effect was −3.74 (95% confidence interval, −4.50 to −2.98), indicating lower MCP-1/CCL2-related readouts in resveratrol-treated groups than in controls, with substantial heterogeneity (I2 = 78.9%). The negative association was driven mainly by rat and mouse datasets, whereas the piglet estimate was directionally opposite and the rabbit estimate came from a single dataset. Funnel-plot inspection suggested asymmetry, and dose meta-regression did not significantly explain between-study variation (slope = −0.17, p = 0.482). Leave-one-out and cumulative analyses indicated directional stability but did not resolve the underlying heterogeneity. Conclusions: These preclinical data indicate lower MCP-1/CCL2-related readouts after resveratrol treatment, but high heterogeneity, PubMed-only retrieval, and pharmacokinetic limitations limit direct clinical inference. Full article

Background/Objectives: The rapid growth of the global aging population, projected to reach 2.1 billion older adults by 2050, presents major challenges for pharmacotherapy and drug delivery. Age-related physiological changes affecting pharmacokinetics and pharmacodynamics, widespread polypharmacy, and functional impairments such as dysphagia, cognitive decline, and sensory or motor limitations reduce the effectiveness and safety of conventional “one-size-fits-all” medication approaches. This review aimed to evaluate the major barriers to effective drug delivery in older adults and to assess emerging patient-centered and technology-driven drug delivery systems designed to improve medication adherence, safety, and therapeutic outcomes in geriatric populations. Methods: A comprehensive narrative review of current literature was conducted focusing on geriatric pharmacotherapy, age-related barriers to medication administration, and advanced drug delivery technologies. The review analyzed evidence regarding modified oral formulations, transdermal systems, long-acting injectables, implantable devices, nanotechnology-based platforms, digital health integrations, pharmacogenomics, biomarker-guided therapy, and deprescribing strategies including STOPP/START criteria and Beers Criteria. Studies addressing polypharmacy, medication adherence, and personalized medicine in older adults were also evaluated. Results: Evidence indicates that older adults experience significant medication-related challenges due to multimorbidity, polypharmacy, and functional decline. Dysphagia affects more than half of nursing home residents, while polypharmacy prevalence reaches up to 86.6% in some populations. Emerging drug delivery technologies demonstrated potential to improve adherence, dosing precision, and patient convenience. Personalized approaches incorporating pharmacogenomics, biomarker-guided treatment, and AI-assisted dosing showed promise for optimizing therapy. However, major limitations remain, including underrepresentation of older adults in clinical trials, limited high-quality evidence supporting many polypharmacy interventions, and insufficient implementation of advanced drug delivery systems in routine clinical practice. Conclusions: Current evidence supports a transition from standardized medication approaches toward flexible, individualized, and patient-centered drug delivery strategies for older adults. Advanced delivery technologies and personalized pharmacotherapy may improve medication safety, adherence, and quality of life in aging populations, although stronger clinical evidence and broader implementation are still needed. Future progress will require interdisciplinary care models, improved geriatric representation in clinical research, and regulatory reforms supporting the integration of innovative drug delivery systems into routine healthcare practice. Full article