Search Results (67)

Artificial intelligence (AI) is increasingly influencing nanopharmaceutical development by supporting the transition from empirical formulation screening toward predictive, data-driven, and translationally oriented design. Nanocarrier-based therapeutics are governed by nonlinear relationships among material composition, physicochemical attributes, manufacturing parameters, biological identity, pharmacokinetics, toxicity, and therapeutic performance. In this review, we examine how AI can contribute to nanopharmaceutical development from predictive formulation design to clinical translation. We synthesize current applications of machine learning, deep learning, physics-informed modeling, hybrid mechanistic–AI approaches, and automated optimization workflows, with emphasis on critical quality attribute modeling, multi-objective optimization, design of experiments, quality-by-design, process analytical technology, digital twins, and continuous manufacturing. We also discuss applications involving nano–bio interactions, pharmacokinetics, toxicity, immunogenicity, and precision nanomedicine. AI-based approaches can support rational nanocarrier design, identify nonlinear formulation–property relationships, guide optimization, improve process understanding, and integrate heterogeneous experimental, biological, and manufacturing datasets across diverse nanopharmaceutical platforms. These methods are particularly relevant for modeling protein corona formation, cellular uptake, intracellular trafficking, biodistribution, pharmacokinetics, toxicity, immunogenicity, and patient-specific responses. However, translational implementation remains limited by fragmented datasets, inconsistent reporting standards, limited interpretability, insufficient external validation, uncertain predictions, poorly defined applicability domains, and evolving regulatory expectations for adaptive computational models. Overall, AI should be viewed not only as an optimization tool, but also as a translational framework connecting formulation science, biological prediction, manufacturing control, and clinical implementation. Future progress will depend on standardized data infrastructures, explainable and externally validated models, uncertainty quantification, applicability-domain definition, hybrid mechanistic–AI frameworks, regulatory-ready documentation, and clinically relevant case studies. Full article

Background: Uveal melanoma is the most common intraocular malignancy in adults with a poor prognosis. Although local therapies are effective, treatment options for advanced disease remain limited. Combination strategies using chemotherapeutic agents and natural compounds, such as quercetin, are in focus for their potential to enhance antitumor efficiency and overcome resistance. Methods: The effects of doxorubicin, quercetin, and their combination were investigated in uveal melanoma cell lines. Cell viability was determined by an MTT assay, and apoptosis and cell cycle distribution by flow cytometry. Invasion assays were performed to evaluate metastatic potential, while modifications in signaling pathways were analyzed by Western blotting and qPCR. Results: Both doxorubicin and quercetin significantly reduced cell viability and induced apoptotic and necrotic cell death. The combination treatment demonstrated additional inhibitory effects in both cell lines, shown by increased SubG1 populations, reduced invasive capacity, and modulation of signaling pathways. Cell cycle analysis indicated treatment-induced growth inhibition. Notably, pathway modifications varied between cell lines, suggesting heterogeneous responses. Conclusions: Quercetin may potentiate certain antitumor effects of doxorubicin in uveal melanoma, particularly by reducing post-treatment invasiveness and modulating certain PI3K/AKT pathway-related proteins. These results support the possibility of quercetin-based combination therapies, although further molecular and in vivo studies are required. Full article

The rational design of mixed micellar systems has emerged as a cornerstone of modern nanomedicine, offering unprecedented control over the solubility and bioavailability of challenging therapeutic agents. This review provides a comprehensive analysis of the physicochemical principles governing the assembly of amphiphilic drugs and surfactants into synergistic nanostructures. By articulating the transition from traditional guest/host solubilization to “drug-as-component” models, we highlight the critical role of molecular interactions in achieving therapeutic precision. It further outlines the experimental methodologies used to investigate these systems and elucidates how they enhance the solubility, stability, and bioavailability of poorly water-soluble drugs. Special emphasis is placed on the practical applications of synergy in reducing systemic toxicity and optimizing drug release kinetics, providing a roadmap for the development of next-generation nano-pharmaceuticals. The functionality of these systems is significantly influenced by the molecular interactions among their constituents; thus, quantitative analysis of these interactions might enhance the formulation of more effective pharmaceuticals. This review outlines the key physicochemical principles of mixed micelle formation, including thermodynamics and synergistic interactions of amphiphiles, while emphasizing their relevance in current research and practical pharmaceutical applications. Various experimental methods, such as surface tension measurement, conductometric and calorimetric tests, and spectroscopic techniques, are compared in terms of their conditions of application and performance in understanding micelle formation and micelle structure. We clearly point out that the interpretation and evaluation of the properties of colloidal systems containing drug molecules solubilized by mixed micelles and an amphiphilic drug incorporated into micelles must be discussed and evaluated separately. Understanding the limitations and characteristics of the physical/chemical principles applied is essential for the rational design of mixed micelle carriers tailored to specific therapeutic needs. Full article

Background/Objectives: Intracellular delivery of RNA molecules is challenging. To solve this problem, many carrier systems are available, which are based on liposomes or polymers. Cyclodextrins are widely used excipients to increase the solubility of small molecules, but their polymer derivatives are able to deliver macromolecules. In the present study, we aimed to investigate and compare the siRNA and mRNA carrying capacity of a cationic quaternary ammonium β-cyclodextrin polymer (QABCDPS) and polyethylenimine (PEI). Methods: Cytotoxicity of the polymers was tested by the MTT method. Polyplexes were formulated with different nitrogen/phosphate ratios (NP), and their physicochemical properties were examined using dynamic light scattering and zeta potential measurements. Cellular internalization and intracellular effects of the polyplexes were investigated by confocal microscopy and flow cytometry. Results: QABCDPS exhibited lower toxicity compared to PEI, effectively binding both siRNA and mRNA and delivering them into vesicles in the cytoplasm, but showing different internalization patterns. Polyplexes formed with PEI showed stronger biological effect than those with QABCDPS, which can be attributed to the strength of interactions facilitated by the polymers. Conclusions: In summary, QABCDPS is a low-toxicity carrier that shows some promise for mRNA delivery but is ineffective for siRNA silencing under the tested conditions and requires further structural optimization. Full article

Lab-on-a-Chip (LoC) and microfluidic technologies are rapidly reshaping the development pipeline for nano drug delivery systems (DDSs) by enabling precise control of physicochemical properties, high-throughput screening, and integrated biological evaluation within miniaturized platforms. This review synthesizes recent advances in microfluidic principles, fabrication strategies, and sensing modalities that facilitate continuous flow synthesis, real-time characterization, and adaptive formulation of nanoparticles. We highlight how LoC-enabled systems improve monodispersity, reproducibility, and tunability of liposomes, polymeric nanoparticles, and metallic nanocarriers, while providing powerful tools for assessing pharmacokinetics, drug release, and systemic responses using organ-on-chip (OoC) models. Emerging trends, including AI-driven autonomous optimization, stimuli-responsive materials, 3D-printed hybrid architectures, and self-powered portable devices, are discussed in the context of future integrated nano-pharmaceutics platforms. Despite existing challenges related to biocompatibility, standardization, data integration, and translation to industrial and clinical applications, the synergistic evolution of LoC engineering and nanomedicine holds transformative potential for personalized and next-generation therapeutic strategies. Full article

Background: Menopause is characterised by a decline in oestrogen levels, leading to physical and psychological symptoms that significantly affect quality of life. Current parenteral oestradiol ester therapies, while effective, are often associated with side effects due to their oil-based formulations, including injection-site reactions and immune responses. Methods: In this study, we developed a water-soluble, polyethylene glycol cross-linked β-cyclodextrin (PEG–β-CD) polymer-based system for parenteral oestradiol delivery and evaluated its biocompatibility, solubility enhancement, immune compatibility, and pharmacokinetics. Results: Cytotoxicity assays using NIH-3T3 fibroblasts and RAW 264.7 macrophages showed minimal toxicity up to 10% (w/w). Phase-solubility studies demonstrated a significant increase in oestradiol solubility with the PEG–β-CD polymer, surpassing that of β-cyclodextrin or PEG alone. Dynamic light scattering and FTIR analyses confirmed successful complex formation, with submicron particles averaging 271 nm and physical incorporation of oestradiol into the polymer matrix. Macrophage activation assays and RT-qPCR analyses indicated an absence of immunogenic responses or pro-inflammatory cytokine induction. In vivo toxicity testing in Galleria mellonella larvae confirmed safety, while pharmacokinetic studies in Wistar rats revealed rapid initial absorption followed by stable, low-level serum concentrations comparable to those of commercially used oestradiol esters. Conclusions: These findings indicate that the PEG–β-CD polymer–oestradiol complex provides a safe, water-based alternative to traditional oil-based injections, with the potential to reduce side effects and improve patient compliance in postmenopausal hormone therapy. Full article

Quantitative analyses in drug-delivery research are frequently distributed across multiple tools, which increases manual handling and the risk of transcription errors. NanoEDW 1.0 is an open source Python application that integrates calibration-curve generation, encapsulation-efficiency (EE%) calculation, and release kinetics modeling in a single, streamlined workflow. This study aims to validate the performance of NanoEDW 1.0 by benchmarking it against spreadsheet/OriginLab^® OriginPro 2025 analyses on experimental datasets from polymeric nanocarrier systems commonly used in drug encapsulation. The software performs linear regression to convert absorbance into concentration, computes EE% from raw experimental values, and fits drug-release profiles to classical models (including zero/first-order, Higuchi, Korsmeyer–Peppas, Weibull, and Modified Gompertz) using non-linear least squares with standard goodness-of-fit metrics (R², RMSE). Results show close agreement with reference workflows for calibration parameters and EE%, as well as statistically comparable release-model fits, while reducing manual steps and analysis time. In conclusion, the validation confirms that NanoEDW 1.0 can streamline routine analyses and enhance reproducibility and accessibility in nanopharmaceutical research; source code and example datasets are provided to foster adoption. Full article

Flavonoids play an important role in preventive and therapeutic research due to their significant antioxidant properties. However, their application is limited by several pharmacokinetic drawbacks, such as poor water solubility and low bioavailability. Cyclodextrin-based delivery systems offer an opportunity to overcome these disadvantages. Cyclodextrins are able to form stable, water-soluble inclusion complexes with flavonoids, thereby improving their solubility, chemical stability, and antioxidant activity. This review summarizes the structural characteristics and complexation mechanisms of various flavonoid–cyclodextrin complexes and examines how these interactions influence biological activity. Special attention is given to nanotechnological formulations—such as liposomes, nanofibers, and nanosponges—that enable targeted drug delivery and enhanced therapeutic efficacy. The aim of this review is to provide a comprehensive overview of the role of cyclodextrin-based carriers in the formulation of flavonoids and to highlight the future potential of these systems in modern therapeutics and functional product development. Full article

Nanodrugs hold great promise for targeted therapies, but their potential for cytotoxicity remains a major area of concern, threatening both patient safety and clinical translation. In this systematic review, we conducted a systematic investigation of nanotoxicity studies—identified through an AI-assisted screening procedure using Scopus, PubMed, and Elicit AI—to establish the molecular determinants of nanodrug-induced cytotoxicity. Our findings reveal three dominant and linked mechanisms that consistently act in a range of nanomaterials: oxidative stress, inflammatory signaling, and lysosomal disruption. Key nanomaterial properties like chemical structure, size, shape, surface charge, tendency to aggregate, and biocorona formation control these pathways, modulating cellular uptake, reactive oxygen species generation, cytokine release, and subcellular injury. Notably, the most frequent mechanism was oxidative stress, which often initiated downstream inflammatory and apoptotic signaling. By linking these toxicity pathways with particular nanoparticle characteristics, our review presents necessary guidelines for safer, more biocompatible nanodrug formulation design. This extensive framework acknowledges the imperative necessity for mechanistic toxicity assessment in nanopharmaceutical design and underscores the strength of AI tools in driving systematic toxicology studies. Full article

Background/Objectives: Continuous manufacturing is gaining importance in the nanopharmaceutical field, offering improved process efficiency and product consistency. To fully leverage its potential, the integration of Process Analytical Technology (PAT) tools is essential for real-time quality control and robust process monitoring. Among the critical quality attributes (CQAs) of nanosystems, particle size plays a key role in ensuring product consistency and performance. However, real-time size monitoring remains challenging due to complex process dynamics and nanosystem heterogeneity. Methods: This study evaluates the applicability of conventional Dynamic Light Scattering (DLS) and spatially resolved DLS (SR-DLS) using the NanoFlowSizer (NFS) as PAT tools in a temperature-regulated top-down nano-production line. Various lipid-based nanosystems, including solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC), and nanoemulsions (NEs), were investigated. To ensure reliable implementation, key factors such as sample dilution, viscosity, focus position, measurement angle and temperature effects were systematically assessed for offline and at-line DLS using the Litesizer 500, as well as for offline, inline, and online SR-DLS using the NFS. Results: Offline screening confirmed that selecting the appropriate dilution medium and rate ensures measurement reliability. At-line methods provided an efficient alternative by enabling rapid final product control with minimal manual intervention. Inline and online monitoring further enhanced process efficiency by enabling real-time tracking of size, reducing waste, and allowing immediate process adjustments. Conclusions: This study demonstrates that integrating offline, at-line, in-line, and online DLS techniques allows for comprehensive product monitoring throughout the entire production line. This approach ensures a streamlined process, enables real-time adjustments, and facilitates reliable quality control after production and during storage. Full article

Nanoparticles (NPs) represent a unique class of structures in the modern world. In comparison to macro- and microparticles, NPs exhibit advantages due to their physicochemical properties. This has resulted in their extensive application not only in technical and engineering sciences, but also in pharmacy and medicine. A recent analysis of the scientific literature revealed that the number of articles related to the search term “nanoparticle drugs” has exceeded 65,000 in the last decade alone, according to PubMed. The growth of scientific publications on NPs and nanomaterials (NMs) in pharmacy demonstrates the rapidly developing interest of scientists in exploring alternative ways to deliver drugs, thereby improving their pharmacokinetic and pharmacodynamic properties, and the increased biocompatibility of many nanopharmaceuticals is a unique key to two mandatory pharmaceutical requirements—drug efficacy and safety. A comprehensive review of the literature indicates that the modern pharmaceutical industry is increasingly employing nanostructures. The exploration of their physicochemical properties with a subsequent modern approach to quality control remains the main task of modern pharmaceutical chemistry. The primary objective of this review is to provide a comprehensive overview of data on NPs, their physicochemical properties, and modern approaches to their synthesis, modification of their surface, and application in pharmacy. Full article

Colorectal cancer (CRC) represents one of the most serious health issues and the third most commonly diagnosed cancer worldwide. However, the treatment options for CRC are associated with adverse reactions, and in some cases, resistance can develop. Flavonoids have emerged as promising alternatives for CRC prevention and therapy due to their multitude of biological properties and ability to target distinct processes involved in CRC pathogenesis. Their innate disadvantageous properties (e.g., low solubility and stability, reduced bioavailability, and lack of tumor specificity) have delayed the potential inclusion of flavonoids in CRC treatment regimens but have hastened the design of nanopharmaceuticals comprising a flavonoid agent entrapped in a nanosized delivery platform that not only counteract these inconveniences but also provide an augmented therapeutic effect and an elevated safety profile by conferring a targeted action. Starting with a brief presentation of the pathological features of CRC and an overview of flavonoid classes, the present study comprehensively reviews the anti-CRC activity of different flavonoids from a mechanistic perspective while also portraying the latest discoveries made in the area of flavonoid-containing nanocarriers that have proved efficient in CRC management. This review concludes by showcasing future perspectives for the advancement of flavonoids and flavonoid-based nanopharmaceuticals in CRC research. Full article

Background: The excessive accumulation of Aβ plays a critical role in the development of Alzheimer’s disease. However, the therapeutic potential of drugs like curcumin is often limited by low biocompatibility and BBB permeability. In this study, we developed a nanomaterial, BP-PEG-Tar@Cur, which was designed to enhance the biocompatibility of (curcumin) Cur, target Aβ, and augment BBB permeability through near-infrared (NIR) photothermal effects. Methods: Soluble Aβ, ThT fluorescence, and Aβ depolymerization fluorescence experiments were conducted to evaluate the ability of BP-PEG-Tar@Cur to inhibit Aβ aggregation and dissociate Aβ fibrils. Cell uptake assays were performed to confirm the targeting ability of BP-PEG-Tar@Cur towards Aβ. In vitro mitochondrial ROS clearance and in vivo detection of inflammatory factors were used to assess the anti-inflammatory and antioxidant properties of the nanodrug. Water maze behavioral experiments were conducted to evaluate the effect of BP-PEG-Tar@Cur on spatial memory, learning ability, and behavioral disorders in AD mice. Results: The nanodrug effectively inhibited Aβ aggregation and dissociated Aβ fibrils in vitro. BP-PEG-Tar@Cur demonstrated efficiency in curbing ROS overproduction in mitochondria and dampening the activation of microglia and astrocytes triggered by Aβ aggregation. Water maze behavioral experiments revealed that BP-PEG-Tar@Cur enhanced spatial memory, learning ability, and alleviated behavioral disorders in AD mice. Conclusions: Collectively, these findings demonstrate that BP-PEG-Tar@Cur has the potential to be an effective targeted drug for inhibiting Aβ aggregation and improving cognitive impairment in AD mice. Full article

Genitourinary syndrome of menopause (GSM) affects a significant percentage of postmenopausal women and manifests as vaginal dryness, irritation, and urinary discomfort, typically treated with vaginal estrogens. Hydrogels are preferred over creams due to their superior comfort and mucoadhesive properties. This study introduces a novel vaginal gel formulation containing hydroxyethyl cellulose (HEC) and estriol-hydroxypropyl-β-cyclodextrin complex (E3-HPBCD) for the treatment of GSM. The estriol (E3) release profile of the gel was evaluated using a Franz diffusion cell system, and its permeability was tested on reconstructed human vaginal epithelium. Biocompatibility was assessed using (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) (MTT), lactate dehydrogenase (LDH) assays, and real-time cell analysis (RTCA) on human skin keratinocyte (HaCaT) cells, which showed increased cell viability and no obvious cytotoxicity. The results indicated that efficient E3 release and satisfactory epithelial permeability with HPBCD provide the bioavailability of E3. These results suggest the potential of the gel as a biocompatible and effective alternative for the treatment of GSM. Further studies are required to assess the long-term safety and clinical efficacy. Full article

Hyaluronic acid (HA) is a naturally occurring, long, unbranched polysaccharide that plays a critical role in maintaining skin structure and hydration. Its unique properties make it a valuable component in the field of nanopharmaceuticals. The combination of HA into nanopharmaceuticals enhances its ability to interact with various therapeutic agents, improving the delivery and efficacy of drugs. HA-based nanoparticles, including solid lipid nanoparticles, and polymeric nanogels, offer controlled release, enhanced stability, and targeted delivery of therapeutic agents. These innovations significantly improve therapeutic outcomes and reduce side effects, making HA an essential tool in modern medicine. In general, HA-modified liposomes enhance drug encapsulation and targeting, while HA-modified solid lipid nanoparticles (SLNs) provide a solid lipid core for drug encapsulation, offering controlled release and stability. This article provides an overview of the potential applications and recent advancements of HA in nanopharmaceuticals, emphasizing its significant impact on the evolving field of targeted drug delivery and advanced therapeutic strategies. By delving into the unique properties of HA and its compatibility with various therapeutic agents, this review underscores the promising potential of HA in revolutionizing nanopharmaceuticals. Full article