Search Results (591)

Background/Objective: The primary cilium is the sensory organelle of a cell and a dynamic membrane protrusion during the cell cycle. It originates from the centriole at G₀/G₁ and undergoes disassembly to release centrioles for spindle formation before a cell enters mitosis, thereby serving as a cell cycle checkpoint. Cancer cells that undergo rapid cell cycle and replication have a low ciliation rate. In this study, we aimed to identify cilia-promoting drugs that can accelerate ciliation and decelerate replication of cancer cells. Methods: To perform a comprehensive and efficient literature search on drugs that can promote ciliation, we developed an intelligent process that integrates either the GPT 4 Turbo, Gemini 1.5 Pro, or Claude 3.5 Haiku application programming interfaces (APIs) into a PubMed scraper that we coded, enabling the large language models (LLMs) to directly query articles for predefined user questions. We evaluated the performance of this intelligent literature search based on metrics and tested the effect of two candidate drugs on ciliation and proliferation of medulloblastoma cells. Results: Gemini was the best model overall, as it balanced high accuracy with solid precision and recall scores. Among the top candidate drugs identified are Alvocidib and Alisertib, small-molecule inhibitors of CILK1 and AURKA, respectively. Here, we show that both kinase inhibitors can effectively increase cilia frequency and significantly decrease the replication of medulloblastoma cells. Conclusions: The results demonstrated the potential of using cilia-promoting drugs, such as Alvocidib and Alisertib, to suppress cancer cell replication. Additionally, it shows the massive benefits of integrating accessible large language models to conduct sweeping, rapid, and accurate literature searches. Full article

Inflammation is strongly related to the development of multiple chronic diseases, such as cardiovascular and autoimmune diseases, and is considered a crucial target for new therapeutic approaches, since it significantly impacts public health, contributes to high mortality rates, and decreases the quality of life. Conventional anti-inflammatory approaches are commonly used, but they present multiple limitations, such as undesirable side effects and low target-specificity. Medicinal plants and their bioactive phytochemical compounds have been studied in recent years and are considered promising alternatives to classical therapies. They are widely recognized for their capacity to modulate inflammatory pathways, regulate inflammatory responses, and consequently reduce inflammation and related symptoms. Although they are considered a good therapeutic alternative, their application in the human body is limited by certain characteristics, such as low solubility, which leads to rapid metabolism and excretion by the organism, significantly reducing bioavailability; for these reasons, the use of medicinal plants remains a biopharmaceutical challenge. Nanotechnology represents a promising tool in this context, since it can improve several characteristics of these compounds. By incorporating plant-derived compounds in nanosystems, considerable advantages, including sustained release, protection from degradation, an increase in the specificity to target tissues, and consequent reduction in toxicity, can be achieved. Thus, nanosystems promote more favorable therapeutic outcomes. This work aims to compile scientific evidence supporting the use of medicinal plants and their bioactive phytochemical compounds, incorporated in nanosystems, in inflammatory disorders. This review enlarges knowledge by integrating both in vitro and in vivo studies involving multiple medicinal plants and bioactive phytochemical compounds, describing their mechanisms of action and the nanosystems employed for drug delivery. In the future, the need for deeper mechanistic studies, the development of targeted and stimuli-responsive systems, and advancement toward clinically translatable, sustainable, and cost-effective plant-based nanotherapies is required. Full article

Background: Solid organ transplantation (SOT) is a life-saving treatment for patients with end-stage diseases and/or organ failure. However, access to healthy organs is often limited by challenges in organ preservation. Furthermore, upon transplantation, ischemia–reperfusion injury (IRI) can lead to increased organ rejection or graft failures. The work presented aims to address both challenges using an innovative nanomedicine platform for simultaneous drug and oxygen delivery. In recent studies, resveratrol (RSV), a natural antioxidant, anti-inflammatory, and reactive oxygen species (ROS) scavenging agent, has been reported to protect against IRI by inhibiting ferroptosis. Here, we report the design, development, and scalable manufacturing of the first-in-class dual-function perfluorocarbon-nanoemulsion (PFC-NE) perfusate for simultaneous oxygen and antioxidant delivery, equipped with a near-infrared fluorescence (NIRF) reporter, longitudinal, non-invasive NIRF imaging of perfusate flow through organs/tissues during machine perfusion. Methods: A Quality-by-Design (QbD)-guided optimization was used to formulate a triphasic PFC-NE with 30% w/v perfluorooctyl bromide (PFOB). Drug-free perfluorocarbon nanoemulsions (DF-NEs) and RSV-loaded nanoemulsions (RSV-NEs) were produced at 250–1000 mL scales using M110S, LM20, and M110P microfluidizers. Colloidal attributes, fluorescence stability, drug loading, and RSV release were evaluated using DLS, NIRF imaging, and HPLC, respectively. PFC-NE oxygen loading and release kinetics were evaluated during perfusion through the BMI OrganBank^® machine with the MEDOS HILITE^® oxygenator and by controlled flow of oxygen. The in vitro antioxidant activity of RSV-NE was measured using the oxygen radical scavenging antioxidant capacity (ORAC) assay. The cytotoxicity and ferroptosis inhibition of RSV-NE were evaluated in RAW 264.7 macrophages. Results: PFC-NE batches maintained a consistent droplet size (90–110 nm) and low polydispersity index (<0.3) across all scales, with high reproducibility and >80% PFOB loading. Both DF-NE and RSV-NE maintained colloidal and fluorescence stability under centrifugation, serum exposure at body temperature, filtration, 3-month storage, and oxygenation. Furthermore, RSV-NE showed high drug loading and sustained release (63.37 ± 2.48% at day 5) compared with the rapid release observed in free RSV solution. In perfusion studies, the oxygenation capacity of PFC-NE consistently exceeded that of University of Wisconsin (UW) solution and demonstrated stable, linear gas responsiveness across flow rates and FiO₂ (fraction of inspired oxygen) inputs. RSV-NE displayed strong antioxidant activity and concentration-dependent inhibition of free radicals. RSV-NE maintained higher cell viability and prevented RAS-selective lethal compound 3 (RSL3)-induced ferroptosis in murine macrophages (macrophage cell line RAW 264.7), compared to the free RSV solution. Morphological and functional protection against RSL3-induced ferroptosis was confirmed microscopically. Conclusions: This study establishes a robust and scalable PFC-NE platform integrating antioxidant and oxygen delivery, along with NIRF-based non-invasive live monitoring of organ perfusion during machine-supported preservation. These combined features position PFC-NE as a promising next-generation acellular perfusate for preventing IRI and improving graft viability during ex vivo machine perfusion. Full article

Background: Solid microneedles (MNs) are effective transdermal delivery devices but are commonly fabricated from metallic or non-biodegradable materials, raising concerns related to sustainability, waste management, and processing constraints. This study aimed to evaluate the suitability of the biodegradable biopolyester poly(3-hydroxybutyrate-co-3-hydroxyvalerate-co-3-hydroxyhexanoate) (PHBHVHHx) as a structuring material for solvent-free fabrication of solid MN arrays and to assess their mechanical performance, insertion capability, and drug delivery potential. Methods: PHBHVHHx MN arrays were fabricated by solvent-free micromolding at 200 °C. The resulting MNs were morphologically characterized by scanning electron microscopy. Mechanical properties were assessed by axial compression testing, and insertion performance was evaluated using a multilayer Parafilm skin simulant model. Diclofenac sodium was used as a model drug and applied via surface coating using a FucoPol-based formulation. In vitro drug release was assessed in phosphate-buffered saline under sink conditions and quantified by UV–Vis spectroscopy. Results: PHBHVHHx MN arrays consisted of sharp, well-defined conical needles (681 ± 45 µm length; 330 µm base diameter) with micro-textured surfaces. The MNs withstood compressive forces up to 0.25 ± 0.03 N/needle and achieved insertion depths of approximately 396 µm in the Parafilm model. Drug-coated MNs retained adequate mechanical integrity and exhibited a rapid release profile, with approximately 73% of diclofenac sodium released within 10 min. Conclusions: The results demonstrate that PHBHVHHx is a suitable biodegradable thermoplastic for the fabrication of solid MN arrays via a solvent-free process. PHBHVHHx MNs combine adequate mechanical performance, reliable insertion capability, and compatibility with coated drug delivery, supporting their potential as sustainable alternatives to conventional solid MN systems. Full article

This study aimed to control rapid localized corrosion and inflammation of biodegradable magnesium implants by developing a pH-responsive mPEG-PLGA coating loaded with dexamethasone (Dex). The mPEG-PLGA layer was designed to selectively degrade in alkaline conditions, thereby moderating pH elevation at the implant surface while enabling controlled Dex release. By varying the molecular weight of mPEG and PLGA, the degradation rate and microsphere size were tunable, allowing adjustment of the drug release profile. Among the tested coating solution concentrations (1.5–7.5 mg/mL), the formulation with 3 mg/mL Dex yielded a final cumulative release concentration of 0.02 mg/mL over a two-week period, which suppressed inflammatory responses in RAW 264.7 macrophages with minimal cytotoxicity, while enhancing BMP-2 and RUNX2 expression in mesenchymal stem cells. In a rat femur defect model, Mg implants coated with mPEG-PLGA containing 3 mg/mL Dex significantly increased bone volume and bone mineral density and reduced early TNF-α expression, accompanied by continuous new bone formation and strong BSP-positive osseointegration. These findings suggest that the proposed pH-responsive mPEG-PLGA/Dex coating provides a promising strategy to simultaneously regulate corrosion, attenuate inflammation, and promote bone regeneration around magnesium implants. Full article

Bleeding and thromboembolism are among the leading causes of mortality worldwide. Thrombosis encompasses both arterial forms—primarily associated with atherosclerosis and leading to heart attacks or strokes—and venous forms. Microvascular thrombosis typically arises in the context of sepsis or systemic inflammation, and it became particularly prominent during the COVID-19 pandemic, substantially contributing to increased mortality. Given this burden, the rapid development of new therapies using advanced techniques and materials to prevent and treat these conditions is essential. This review summarizes recent advances in the design of antithrombotic polymers, discussing mechanisms of action, surface-modification strategies, and current clinical and preclinical applications. It also outlines criteria for evaluating hemocompatibility, describes in vitro and in vivo testing methods, and highlights key barriers to translating these materials into clinical practice. The review concludes by identifying promising directions for future research, including multifunctional approaches that combine antifouling properties, controlled drug release, and bioresistance strategies with the greatest potential to reduce thromboembolic complications associated with medical materials. It further evaluates the progress made to date in combating thrombotic diseases and identifies remaining gaps in the development and clinical implementation of new antithrombotic materials. Full article

The naturally occurring, biocompatible and biodegradable biopolymer dextran is a versatile material for the formulation of hydrogels with desirable properties for use in medicine, drug delivery, and tissue engineering applications. The distinctive structural and physicochemical characteristics, such as polymeric nature, gelling ability and excellent swelling properties, present it as an excellent biomaterial for drug delivery. This study explores the synthesis and characterization of dextran hydrogel for the encapsulation of clindamycin as an innovative approach for controlled drug delivery. The dextran hydrogel was synthesized through a simple and cost-effective method, and its swelling behavior, temperature and pH dependence, and surface morphology were investigated. The maximum equilibrium swelling ratio (73 ± 1%) of the hydrogel was observed in water at 25 °C within 120 min, and the hydrogel was found to be pH- and temperature-dependent for more precise and targeted drug delivery. Moreover, the dextran hydrogel was found to retain water for up to 18 h and remain stable for 8 days. The presence of a roughened surface with large openings/pores on the surface illustrated the high swelling capability of the synthesized hydrogel. In addition, the dextran hydrogel loaded with clindamycin demonstrated high drug loading capacity (70 ± 2%), rapid (65 ± 2%) in vitro drug release potential and pathogen-inhibitory activity against Staphylococcus gallinarium and Bacillus subtilis. Full article

Quercetin’s therapeutic potential is limited by its poor water solubility and rapid degradation. Natural clay minerals such as kaolinite present sustainable platforms for drug delivery, yet the molecular mechanisms of drug encapsulation are not fully understood. Specifically, the role of kaolinite’s structural polarity, its hydrophilic aluminol (001) and hydrophobic siloxane (00-1) basal surfaces, in selective drug adsorption remains unexplored. This study combines Monte Carlo sampling and Density Functional Theory (DFT) to provide the first quantitative, atomistic comparison of quercetin adsorption on both kaolinite surfaces. The results demonstrate a pronounced polarity-driven selectivity. Strong, exothermic adsorption (−206.65 kJ mol⁻¹) occurs on the hydrophilic (001) surface, stabilized by a network of five hydrogen bonds. In contrast, the hydrophobic (00-1) surface exhibits significantly weaker sorption (−147.16 kJ mol⁻¹), dominated by van der Waals interactions. Charge-transfer analysis shows that the hydrophilic (001) surface exhibits a net charge transfer of −0.198 e, approximately 2.4 times greater than that of the hydrophobic (00-1) surface (−0.083 e), consistent with differential electron density maps and partial density of states. By linking hydrogen bonding and charge transfer to adsorption energy, these results elucidate how surface polarity dictates drug encapsulation. This work establishes a predictive framework for designing kaolinite-based nanocarriers with optimized stability, bioavailability, and controlled release, guiding the development of sustainable drug delivery systems. It is noted that this DFT study models adsorption at 0 K using periodic slab models in a vacuum. Full article

Polymeric micelles have the potential to improve the efficacy and safety of drug delivery by improving drug solubility, enhancing bioaccumulation and reducing off-target toxicity. Despite excellent safety profiles, a major limitation with polymeric micelles is their inability to rapidly release their payload once they have reached their target, leading to the inadequate delivery of therapeutic doses. To address this limitation, we have developed a novel strategy to impart pH-responsiveness in non-responsive micelles through the co-encapsulation of oligoelectrolytes with drugs. Herein, we investigate the influence of copolymer composition and drug identity in combination with oligoelectrolyte—oligo(2-vinyl pyridine) (OVP)—loading on pH-triggered drug release from micelles and their cytotoxicity. A library of OVP-loaded micelles was prepared using conventional and well-established non-responsive block copolymers. Dynamic light scattering (DLS) was used to monitor the changes in the micelles as a function of pH. Regardless of the copolymer composition, an abrupt decrease in the hydrodynamic diameter (D_h) was observed as the pH was reduced due to OVP expulsion from the core, which was also confirmed by release studies. In general, co-encapsulation of OVP and model drugs (doxorubicin (DOX), gossypol (GP), paclitaxel (PX), and 7-ethyl-10-hydroxycamptothecin (SN38)) in the micelles provided good to excellent encapsulation efficiency percentage (EE%) values. In vitro studies revealed the pH triggered release of drugs from the OVP-loaded micelles regardless of the drug identity, which increased as the OVP loading increased. This general behaviour was observed in all cases, largely independent of the copolymer composition, albeit with subtle differences in the release profile for different drugs. Compared to their blank counterparts, the drug-loaded micelles displayed a slight increase in cytotoxicity against a panel of cancer cell lines, in a dose dependent manner. However, drug- and OVP-loaded micelles displayed a significant increase in cytotoxicity (up to 8-fold increase) that was independent of the copolymer composition. These results demonstrate the versatility of the oligoelectrolyte-mediated approach to furnish non-responsive micelles with a pH-trigger that allows the rapid release of drugs, regardless of the micelle composition or the drug identity. Full article

Background/Objectives: Small-cell lung cancer (SCLC) is an aggressive neuroendocrine malignancy characterized by rapid proliferation, early metastasis, and near-universal relapse after initial therapy. While chemo-immunotherapy modestly improves first-line outcomes, survival after progression remains poor and highlights the urgent need for biomarker-directed strategies. Methods: A comprehensive literature search was conducted using major medical databases looking at key relevant studies on SCLC antibody studies. All authors reviewed the literature, assessed study quality, and interpreted the results from each study. Results: Recent advances in antibody–drug conjugates (ADCs) and T-cell engagers (TCEs) have transformed therapeutic development by targeting antigens selectively expressed on SCLC cells, enabling more precise and potentially durable tumor control. DLL3 has emerged as the most clinically relevant target to date, with the bispecific TCE tarlatamab demonstrating meaningful and durable response, manageable cytokine-release toxicity, and ultimately achieving accelerated FDA approval for previously treated extensive-stage SCLC. Concurrently, DLL3-directed ADCs have shown variable efficacy, underscoring the importance of payload selection, linker chemistry, and antigen density. Beyond DLL3, next-generation ADCs targeting TROP2, B7-H3, and SEZ6 have reported encouraging early-phase activity, including response rates exceeding those of existing second-line cytotoxic options, though myelosuppression, interstitial lung disease, and hepatic toxicity remain key considerations. Conclusions: Collectively, these emerging immunotherapies illustrate a shift toward antigen-specific targeting in a disease historically defined by limited therapeutic innovation. Continued optimization of antigen selection, payload and linker engineering, and biomarker-driven trial design will be critical for translating early promise into durable clinical benefit and reshaping the treatment landscape for SCLC. Full article

Background: Lewisite, a potent chemical warfare agent, induces rapid and progressive cutaneous damage, necessitating treatment strategies that offer both immediate decontamination and prolonged therapeutic action. This study aimed to develop and evaluate a composite topical formulation comprising 4-phenylbutyric acid (4-PBA)-loaded emulsomes embedded within a foam vehicle to address both aspects of vesicant-induced skin injury intervention. Methods: Emulsomes composed of a stearic acid–cholesterol solid lipid core stabilized by a lecithin shell were prepared via thin film hydration and optimized by varying lipid ratios and drug loading parameters. Formulations were characterized for drug loading, particle size, and zeta potential. Physicochemical compatibility was assessed using Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) analyses. Stability was evaluated under accelerated refrigerated (25 °C/60% RH) and room temperature (40 °C/75% RH) conditions. The optimized formulation was incorporated into a foam base and evaluated for decontamination efficiency, drug release kinetics, in vitro permeation, and in vivo efficacy. Results: The selected formulation (E2) exhibited high drug loading (17.01 ± 0.00%), monodisperse particle size (PDI = 0.3 ± 0.07), and stable zeta potential (−40 ± 1.24 mV). FTIR and DSC confirmed successful encapsulation with amorphous drug dispersion. The emulsome-foam demonstrated dual functionality: enhanced decontamination (66.84 ± 1.27%) and sustained release (~30% over 24 h), fitting a Korsmeyer–Peppas model. In vitro permeation showed significantly lower 4-PBA delivery from E2 versus free drug, confirming sustained release, while in vivo studies demonstrated therapeutic efficacy. Conclusions: This emulsome-foam system offers a promising platform for topical treatment of vesicant-induced skin injury by enabling both immediate detoxification and prolonged anti-inflammatory drug delivery. Full article

This study reports the development of paclitaxel (PTX)-loaded human serum albumin (HSA) nanoparticles (NPs), surface-decorated with trastuzumab (TMAB), with potential applicability in HER2-oriented delivery. The NPs were obtained via thermally driven self-assembly followed by non-covalent antibody adsorption and they were characterized using Fourier transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), and ζ-potential analysis. The drug association efficiency (%DAE), defined exclusively for PTX, was high for both HSA-PTX and HSA-PTX-TMAB NPs (96.4% and 98.2% w/w, respectively), with loading capacities (%LC) of 8.9% and 7.4%, respectively. TMAB decoration led to a modest increase in mean diameter and a reduction in surface charge, consistent with successful surface modification. Both formulations exhibited rapid early-phase PTX release followed by an apparent stabilization phase, with distinct kinetic behavior between HSA–PTX and HSA–PTX–TMAB NPs. Cytotoxicity in A549 cells after 18 h of exposure showed modest, non-differential effects consistent with controlled release and short-term assessment of non-specific toxicity. Overall, this thermally assembled albumin-based system provides a promising foundation for further evaluation of HER2-oriented PTX delivery. Full article

Background: The R21 malaria vaccine is a next-generation, WHO-prequalified vaccine that was introduced to reduce the burden of clinical malaria. In alignment with WHO recommendations, multi-dose vaccine presentations are preferred for large-scale immunization and inclusion in the Expanded Programme on Immunization (EPI). Accurate protein quantification is a critical quality control parameter for lot release, but it remains challenging when the antigen is present at low protein concentrations or formulated with complex matrices, including adjuvants, stabilizers, and preservatives. Methods: In this study, multiple protein estimation methods including Micro-BCA, BCA, and Bradford assays were evaluated to determine their suitability for quantifying the R21 antigen formulated with Matrix-M1 adjuvant and 2-PE preservative. The Bradford assay was selected as the most appropriate method, based on a comparative assessment of precision, accuracy, and linearity. Further optimization was undertaken to identify suitable buffer systems, and the method was validated in accordance with ICH Q2(R2) guidelines. Results: Validation results demonstrated that the assay is specific, accurate, precise, and repeatable, with a limit of quantitation (LOQ) of 2 µg/mL. The method demonstrated comparable performance to ELISA and was found to be sensitive enough to detect changes in antigen concentration resulting from unintended adsorption of R21 to vial surfaces. The assay offers a rapid, high-throughput, and cost-effective solution for protein quantitation in commercial manufacturing, lot release, and stability studies. The protein content of the drug product, quantified using the Bradford method, demonstrated robust in vivo immunogenicity in both release and stability studies. Conclusions: The robustness and reproducibility of the assay establish a new benchmark in quality control for virus-like particle (VLP)-based vaccines with complex formulations, thereby supporting the precision and reliability required for global malaria prevention efforts. Full article

In physiological environments, several metallic alloys, including titanium, stainless steel, cobalt–chromium, and emerging biodegradable systems such as magnesium (Mg), zinc (Zn), and iron (Fe), offer mechanical properties and biocompatibility suitable for load-bearing implants. With the rapid advancement of 3D printing technologies, these alloys can now be fabricated into patient-specific, complex geometries that enhance both structural performance and functional integration. Beyond serving as structural supports, 3D-printed alloys are increasingly engineered as localized drug-delivery platforms to release anti-inflammatory, antibacterial, anticancer, and osteogenic agents at the implant–tissue interface, addressing the dual clinical needs of site-specific therapy and mechanical stabilization. Nevertheless, this field remains underexplored because studies differ widely in alloy chemistry, surface topography, porosity, coating strategy, drug-loading methods, and release profiles, as well as in how material degradation or passivation interacts with pharmacokinetics. For the first time, this review consolidates drug-loading and elution strategies across 3D-printed alloy platforms, compares therapeutic categories in relation to alloy and coating types, and critically evaluates how the surface microstructure or alloy geometry influences release behavior. Full article

Potassium (K⁺) channel blockers are promising anticancer agents but suffer from off-target toxicities. We designed cross-linked poly-2-Hydroxyethyl methacrylate (HEMA)–pectin nanogels (HPN) to deliver two model blockers—dofetilide (Dof) and azimilide (Azi)—and evaluated their physicochemical properties, release behavior, and in vitro anticancer activity. HPN was synthesized by surfactant-assisted aqueous nanogel polymerization and comprehensively characterized (FTIR, DLS, TEM/SEM, XRD, BET). The particles were monodispersed with a mean diameter ~230 nm, compatible with tumor accumulation via the Enhanced Permeability and Retention (EPR) effect, and exhibited a microporous matrix suitable for controlled release. Drug loading was higher for Dof than for Azi, with DL% values of 82.30 ± 3.1% and 17.84 ± 2.9%, respectively. Release kinetics diverged: Azi-HPN followed primarily first-order diffusion with a rapid burst, whereas Dof-HPN showed mixed zero/first-order behavior. Cytotoxicity was assessed in A549 lung cancer and BEAS-2B bronchial epithelial cells. Both free and nano-formulated blockers were selectively toxic to A549 with minimal effects on BEAS-2B. Notably, a hormesis-like pattern (low-dose stimulation/high-dose inhibition in MTT) was evident for free Dof and Azi; encapsulation attenuated this effect for Dof but not for Azi. Co-administration with paclitaxel (Ptx) potentiated Dof-HPN cytotoxicity in A549 but did not enhance Azi-HPN, suggesting mechanism-dependent drug-drug interactions. Overall, HPN provides a biocompatible platform that improves K⁺ blocker delivery. Full article