Background: Silver nanoparticles (AgNPs) trigger apoptosis in cancer cells, while albumin nanoparticles enable effective drug delivery. This study compares the antitumor and cytotoxic effects of albumin-coated AgNPs (AgNPs-Alb) versus AgNPs on human prostate cancer cell lines. Method: AgNPs-Alb were synthesized and tested against PC3 and LNCaP prostate cancer cell lines. Characterization via Transmission Electron Microscopy (TEM), Dynamic Light Scattering (DLS), and Ultraviolet-Visible (UV-Vis) spectroscopy confirmed their properties. IC50 values were determined using MTT assay, with apoptosis assessed by Annexin-V/PI staining. DNA cell cycle was analyzed by PI staining. Migration, proliferation, and nuclear morphology were evaluated through scratch-wound, colony-forming, and Hoechst staining assays. Gene expression of Snail, E-cadherin, VEGF-C, VEGF-A, Bcl2, Bax, and P53 was analyzed using real-time PCR. Results: The IC50 values for AgNPs and AgNPs-Alb were 48 μM and 32 μM in PC3 cells, and 110 μM and 95 μM in LNCaP cells, respectively. AgNPs-Alb significantly inhibited PC3 cell migration compared to AgNPs (p < 0.001) and Bicalutamide (p < 0.0001). In both cell lines, AgNPs-Alb significantly reduced colony formation compared to AgNPs and Bicalutamide (p < 0.05). Flow cytometry revealed a higher percentage of apoptotic cells in PC3 with AgNPs-Alb treatment compared to AgNPs and Bicalutamide. In LNCaP cells, AgNPs-Alb induced a significantly higher percentage of Sub-G1 cells. AgNPs-Alb treatment caused greater mRNA suppression of VEGF-A and a higher Bax/Bcl2 ratio in PC3 and LNCaP cells (p < 0.05). Additionally, a significant increase in P53 and E-cadherin, alongside a decrease in VEGF-C expression in LnCAP cells, was observed (p < 0.05). Conclusions: This study suggests that AgNPs-Alb have stronger anticancer and cytotoxic effects compared to AgNPs alone against PCa cell lines and higher effects were observed on PC3 cells compared to LnCAP cells.

Background/Objectives: Antimicrobial peptides (AMPs) represent a promising class of therapeutics with diverse biological functions, including antibacterial, anti-fungal, anti-parasitic and anti-tumoral activities. Previous works demonstrated the successful repurposing of the two synthetic AMPs 19-2.5 and 19-4LF for cutaneous leishmaniasis, when the compounds were administered in solution on skin lesions caused by Leishmania major in a BALB/c mouse model. In this research project, we assessed the activity of 19-4LF, 19-2.5, and their hybrid 19-2.5LF derivative when formulated as a cream for topical administration in the same animal model. Methods: The peptides were formulated in DAC cream and applied to the wound of BALB/C mice for 30 days. Lesion progression was monitored using a digital caliper. Parasite burden was measured by qPCR. Parasite viability was assessed using MTT and microscopy imaging assays. Results: The three peptides in cream formulation succeeded in reducing the skin lesion. Peptide 19-4LF was the most potent, followed by 19-2.5LF and then 19-2.5. In addition, 19-4LF was able to significantly reduce the parasite burden in the skin lesions of infected mice, as measured by quantifying L. major Lm18S ribosomal gene mRNA levels using qPCR. Moreover, when combined, the peptides exhibited synergistic effects on L. major promastigotes and significantly reduced the number of amastigotes in infected macrophages. Conclusions: These studies support the approach of repurposing these AMPs as antileishmanial drugs and identify 19-4LF as a lead candidate for further studies. While historical barriers to peptide therapeutics included high production costs, recent advancements in biological fermentation and synthesis strategies have significantly improved their economic viability. Furthermore, the use of nanotechnology delivery systems can reduce the required dosage, further making peptide therapy a sustainable option for neglected diseases, including leishmaniasis.

Background/Objectives: Selection of polymer carriers for targeted drug delivery is typically guided by material availability or trigger responsiveness rather than disease-specific evidence. However, successful preclinical formulations may already encode implicit design rules linking polymer composition to particular pathological environments. This study aimed to identify reproducible material-disease associations across biodegradable polymer systems and to derive formulation-oriented guidance for disease-calibrated carrier selection. Methods: A structured synthesis of 65 preclinical in vivo studies (2020-2025) covering inflammatory bowel disease, arthritis, cardiovascular inflammation, and solid tumors was performed. Extracted variables included polymer family, backbone chemistry, stimulus responsiveness, disease model, and reported therapeutic benefit relative to controls. Associations between polymer composition, trigger mechanisms, and disease categories were analyzed using cross-tabulation, chi-square statistics, Cramér's V, and direction-of-effect synthesis. Results: Distinct material-disease clustering patterns emerged. Ionizable polysaccharide and methacrylate systems (e.g., alginate, chitosan, Eudragit) were strongly associated with intestinal inflammatory models, reflecting reliance on pH- and ion-mediated mechanisms. Enzyme-degradable hyaluronic acid matrices were concentrated in joint and cartilage disorders characterized by protease overexpression. Oxidation-sensitive polyether systems (e.g., PEG-PPS) and redox-active hybrid platforms predominated in atherosclerosis and tumor models, where oxidative stress is a defining pathological feature. Composite and multi-responsive systems were disproportionately represented in tumors, consistent with microenvironmental heterogeneity. Across studies, therapeutic improvement was consistently reported when polymer functional motifs aligned with dominant biochemical drivers of the disease. Conclusions: Successful biodegradable polymer carriers exhibit disease-specific compatibility patterns rather than universal applicability. These recurring associations suggest that polymer selection can be guided by pathological context even in the absence of direct outcome comparisons. The resulting formulation-oriented framework supports rational carrier choice for personalized drug delivery based on disease-specific microenvironment signatures.

Background/Objectives: Alzheimer's disease (AD) is a progressive neurodegenerative disorder for which no disease-modifying therapy that halts or substantially slows disease progression is currently available. Although antibody therapies targeting amyloid β (Aβ) have recently received FDA approval, their high cost, limited efficacy, and potential adverse effects highlight the need for alternative solutions. Therefore, the development of low-molecular-weight compounds capable of reducing toxic Aβ aggregates is of considerable interest. In this study, we investigated the effects of 2,3,4-trihydroxybenzophenone (THB) on the inhibition and disassembly of Aβ1-42 aggregates through in vitro and in vivo experiments. Methods: In vitro assays were performed to evaluate the effects of THB on Aβ1-42 aggregation and fibril disassembly. Cell viability assays and hippocampal slice electrophysiology were conducted to assess neurotoxicity and synaptic function. In vivo effects were examined in Aβ1-42 aggregate-injected mice and in 5 Familial AD mutations (5XFAD) mice using behavioral, histological, and electrophysiological analyses. Results: THB inhibited Aβ1-42 aggregation in a concentration-dependent manner and promoted the disassembly of preformed fibrils. THB attenuated Aβ1-42-induced Neuro2a cell death and restored Aβ1-42 aggregate-associated long-term potentiation (LTP) deficits in hippocampal slices. In Aβ1-42 aggregate-injected and 5XFAD mice, THB reduced amyloid pathology and neuroinflammatory markers and improved synaptic function and memory performance. Conclusions: These findings suggest that THB modulates pathogenic Aβ1-42 assemblies and provides a structural basis for the development of small-molecule modulators of Aβ1-42 aggregation with potential preventive or disease-modifying applications in AD.

Background: Although conventional magnetic functional agents provide a material basis for magnetically mediated tumor therapy, they have long been restricted by the application framework of magnetic resonance imaging (MRI) or magnetic thermal ablation. Methods: This study proposed a repurposing strategy of two mature magnetic functional agents, Fe3O4 nanoparticles and gadopentetic acid (GA), by applying their unique magnetic response properties to enhance magnetic field therapy for glioma. Results: Both magnetic materials, when combined with an external magnetic field (MF), showed a synergistic effect to amplify the therapeutic effect. In the CT-2A glioma-bearing mice model, it resulted in marked suppression of tumor growth, with the growth inhibition (TGI) rate increasing from ~27% after MF therapy alone to 64% and 55% after the Fe3O4- and GA-potentiated MF therapy, respectively. It was proposed that the MF effect on impairing tumor angiogenesis was enhanced, as evidenced by significant reductions in CD31 expression and microvessel density. It disrupted nutrient supply to the tumor, augmenting the tumor suppression efficiency. The reduced infiltration of CD4+ and CD8+ T cells into tumors further confirmed the effective blockade of tumor perfusion. Conclusions: This study established a new paradigm of conventional magnetic materials to enhance the non-thermal physical effects and biological regulatory effects of magnetic field for glioma therapy, instead of only as the imaging agents or magnetic hyperthermia agents.

Background: Bone-seeking radiopharmaceuticals based on bisphosphonates enable targeted therapy of skeletal metastases. They are suitable carriers for therapeutic radionuclides such as terbium-161 (161Tb), a β- emitter that additionally releases short-range conversion and Auger electrons, which may enhance radiation dose delivery to small lesions. This study explored the potential of the well-established DOTA conjugated bisphosphonate BPAMD (4-{[(bis(phosphonomethyl))carbamoyl]methyl}-7,10-bis(carboxymethyl)-1,4,7,10 tetraazacyclododec-1-yl)acetic acid) radiolabeled with 161Tb as a bone-targeted radiopharmaceutical, focusing on the theranostic and radiophysical advantages conferred by the radionuclide. Methods: BPAMD was radiolabeled with 161Tb and 177Lu under mild conditions (pH 4.5, 95 °C, 30 min); subsequently, the radiochemical purity was assessed by radio-TLC. Physicochemical properties (charge, lipophilicity, protein binding), in vitro stability (saline and human serum, 48 h), and hydroxyapatite (HAP) binding were evaluated for [161Tb]Tb-BPAMD. Biodistribution was investigated in healthy Wistar rats (n = 3 per time point) at 2 h, 24 h, and 7 days post-injection. Computational density functional theory (DFT) analyses were performed to explore the coordination chemistry of Tb3+ and Lu3+ with BPAMD. Results: Both complexes achieved a radiochemical yield of greater than 98%. [161Tb]Tb-BPAMD exhibited negative charge, high hydrophilicity (logP = -3.92 ± 0.13), low protein binding (19.07 ± 1.01%), excellent radiochemical stability under simulated physiological conditions (>97% at 48 h), and strong hydroxyapatite affinity (>98% with ≥10 mg HAP). Biodistribution showed high, stable bone uptake (8.06% ID/g at 2 h; 6.70% ID/g at 24 h; 5.31% ID/g at 7 d) with rapid blood clearance (<0.001% ID/g at 24 h) and low non-target retention. To contextualize its performance, [161Tb]Tb-BPAMD was compared with [177Lu]Lu-BPAMD, which demonstrated similarly strong skeletal retention (8.74% ID/g at 2 h; 8.08% ID/g at 24 h; 5.25% ID/g at 7 d) but comparatively higher non-target organ uptake. DFT calculations indicate that both Tb3+ and Lu3+ favor octa-coordinated BPAMD complexes. Conclusions: [161Tb]Tb-BPAMD exhibits excellent radiochemical and pharmacokinetic properties, with enhanced biodistribution selectivity over [177Lu]Lu-BPAMD. Combined with the radiobiological advantages of 161Tb, it represents a promising theranostic candidate for targeted therapy of bone metastases.

The solubilization of poorly water-soluble drugs remains a critical challenge in pharmaceutical research. The formulation of solid dispersions employing mesoporous silica nanoparticles (MSN) constitutes a key strategy for enhancing the hydrophilicity and oral bioavailability of Biopharmaceutics Classification System (BCS) Class II drugs. Although several commercial mesoporous silica excipients have been approved for pharmaceutical use, there remains room for improvement regarding drug loading capacity, stability, and controllability of drug release. Methods: for this purpose, dendritic mesoporous silica nanoparticles (DMSN) with a radial dendritic structure and pH-responsive degradation properties were designed and synthesized using celecoxib (CEL) as the model drug, featuring a pore size of 21.51 nm. CEL was loaded onto DMSN and seven commercial solid dispersion excipients using the solvent evaporation method. Results: owing to its high surface area, pore volume, and radial structure, DMSN achieved 39.72% drug loading in an amorphous state, markedly improving wettability, dissolution, and physical stability. Accelerated stability tests showed that DMSN inhibited recrystallization, outperforming traditional solid dispersions. Pharmacokinetic studies in rats demonstrated that the oral bioavailability of CEL-DMSN was 1.29-fold higher than that of commercial celecoxib capsules. Conclusions: in conclusion, these results confirmed the potential of DMSN in enhancing the stability, promoting oral absorption, and reducing gastrointestinal irritation of poorly soluble drugs.

Local analgesia is a prevalent and cost-effective pain management strategy with minimal systemic side effects. At the same time, nanotechnology has been employed to achieve the sustained release of drugs to prolong the duration of local anesthetics (LAs). However, these traditional nanoformulations lack responsiveness and thus cannot achieve precise pain relief through on-demand administration. The emergence of "intelligent" nanosystems with stimulus-response capabilities has opened up new prospects in pain control. This review summarizes recent advancements in the design and application of triggerable LAs nanoformulations that can be activated by external stimuli such as light, ultrasound, or heat. These systems facilitate precise, patient-specific pain management, transforming the clinical approach from long-term suppression to controllable and on-demand relief. Finally, we discussed the current challenges and future prospects. A deeper understanding of this field will facilitate the development of superior analgesic solutions and ultimately improve the treatment outcomes for patients.

Background/Objectives: For successful wound management, dressings must be maintained in a moist environment to optimally enhance the microenvironment of the wound and efficiently deliver bioactive agents. Sodium humate has demonstrated potential wound-healing activity, although its topical delivery is still a challenge. This study aimed to develop and optimize polysaccharide-based dermal patches incorporating sodium-humate-loaded transferosomes and to assess their physicochemical and wound-healing properties. Methods: Transferosomes were obtained via thin-film hydration and prepared utilizing the Taguchi experimental design based on the impact of lipid content, lipid-to-surfactant ratio, and lipid-to-drug ratio on vesicle size, ζ-potential, and drug entrapment efficiency. The optimized transferosomes were loaded into alginate/HPMC composite dermal patches prepared through solvent evaporation. Results: The optimized transferosome formulation had an average size of 250.9 ± 2.3 nm, a ζ-potential of -3.57 ± 0.25, a high deformability of 93.01 ± 2.41%, and an effective drug-entrapment efficiency of 30.13 ± 1.04%. The use of transferosomes greatly affected patch thickness, moisture content, and surface morphology. A biphasic drug release profile of sodium humate was demonstrated via an in vitro release study, showing an initial burst followed by sustained drug release within 6 h. In vivo evaluation of transferosome-loaded patches showed that the formulations were able to effectively promote wound healing compared with the control. Conclusions: The developed transferosome-embedded alginate/HPMC dermal patches constitute a promising platform for the controlled topical administration of sodium humate and show promising enhancement of wound healing.

Background/Objectives: Dapagliflozin is an SGLT2 inhibitor prescribed for the management of type 2 diabetes mellitus. The drug lowers blood glucose levels by increasing urinary glucose excretion (UGE). Despite established efficacy, dapagliflozin demonstrates significant inter-individual variability in pharmacokinetics (PK) and pharmacodynamics (PD), with potential impact on treatment outcomes. Methods: To evaluate the sources of variability and to support patient stratification and model-informed individualized therapy, we developed a physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) model of dapagliflozin using curated data from 28 clinical studies. This framework integrates absorption, distribution, metabolism, excretion, and pharmacodynamics, and accounts for key determinants of variability including renal and hepatic function, and food effects. Results: The simulations reproduced dose-dependent pharmacokinetics with predicted Cmax and AUC values typically within 10-15% of observed data. Renal impairment reduced UGE by 40-60% despite modest changes in plasma exposure, while hepatic impairment produced only small shifts in PK and PD. The model also reproduced the fed-state reduction of peak concentrations, consistent with the 30-50% decrease reported clinically. Conclusions: All model files, code, and curated datasets are openly available in line with FAIR standards and Open Science practices, enabling transparent and reproducible analyses and providing a mechanistic basis for individualized therapy in type 2 diabetes.