Search Results (2,049)

Poly(organo)phosphazenes (PPZs) are increasingly recognized as versatile biomaterials for drug delivery applications in nanomedicine. Their unique hybrid structure—featuring an inorganic backbone and highly tunable organic side chains—confers exceptional biocompatibility and adaptability. Through precise synthetic methodologies, PPZs can be engineered to exhibit a wide spectrum of functional properties, including the formation of multifunctional nanostructures tailored for specific therapeutic needs. These attributes enable PPZs to address several critical challenges associated with conventional drug delivery systems, such as poor pharmacokinetics and pharmacodynamics. By modulating solubility profiles, enhancing drug stability, enabling targeted delivery, and supporting controlled release, PPZs offer a robust platform for improving therapeutic efficacy and patient outcomes. This review explores the fundamental chemistry, biopharmaceutical characteristics, and biomedical applications of PPZs, particularly emphasizing their role in zero-dimensional nanotherapeutic systems, including various nanoparticle formulations. PPZ-based nanotherapeutics are further examined based on their drug-loading mechanisms, which include electrostatic complexation in polyelectrolytic systems, self-assembly in amphiphilic constructs, and covalent conjugation with active pharmaceutical agents. Together, these strategies underscore the potential of PPZs as a next-generation material for advanced drug delivery platforms. Full article

The pharmaceutical industry faces significant challenges when promising drug candidates fail during development due to suboptimal ADME (absorption, distribution, metabolism, excretion) properties or toxicity concerns. Natural compounds are subject to the same pharmacokinetic considerations. In silico approaches offer a compelling advantage—they eliminate the need for physical samples and laboratory facilities, while providing rapid and cost-effective alternatives to expensive and time-consuming experimental testing. Computational methods can often effectively address common challenges associated with natural compounds, such as chemical instability and poor solubility. Through a review of the relevant scientific literature, we present a comprehensive analysis of in silico methods and tools used for ADME prediction, specifically examining their application to natural compounds. Whereas we focus on identifying the predominant computational approaches applicable to natural compounds, these tools were developed for conventional drug discovery and are of general use. We examine an array of computational approaches for evaluating natural compounds, including fundamental methods like quantum mechanics calculations, molecular docking, and pharmacophore modeling, as well as more complex techniques such as QSAR analysis, molecular dynamics simulations, and PBPK modeling. Full article

Background/Objectives: Hepatocellular carcinoma (HCC) is the predominant form of liver cancer and currently is the second-leading cause of cancer-related mortality globally. Current front-line systemic therapies for advanced HCC offer only modest improvements in patient overall survival. HCC is a sexually dimorphic disease, and cancer progression is driven in part by AR activity. Here, we present novel niclosamide pro-drugs for use in advanced HCC based upon niclosamide’s known anti-AR activity and additional anti-cancer pathway efficacy. Methods: Niclosamide analogs were evaluated for their impacts on the AR protein in two HCC cell lines with different AR phenotypes. Amino acid conjugates of niclosamide were developed, and pharmacokinetic (PK) analyses were conducted to determine improvements in clearance and oral exposure. Finally, niclosamide analogs and amino acid conjugates were evaluated in an in vivo model of HCC. Results: Niclosamide analogs maintained anti-AR properties in HCC. Valine-conjugated niclosamide showed improved oral exposure, positioning it as a potential therapeutic in advanced HCC. Conclusions: Valine–niclosamide improves upon niclosamide’s poor solubility and oral bioavailability, increasing its utility for a variety of therapeutic uses. Further study of valine–niclosamide in advanced HCC and in other cancers or diseases is warranted. Full article

Background/Objectives: Holy basil (Ocimum tenuiflorum L.) essential oil exhibits antioxidant, antimicrobial, and anesthetic activities, mainly due to eugenol, methyl eugenol, and β-caryophyllene. However, its clinical application is limited by poor water solubility, instability, and low bioavailability. This study developed and compared two delivery systems, self-nanoemulsifying drug delivery systems (SNEDDS) and microemulsions (ME), to enhance their stability and fish anesthetic efficacy. Methods: The optimized SNEDDS (25% basil oil, 8.33% coconut oil, 54.76% Tween 80, 11.91% PEG 400) and ME (12% basil oil, 32% Tween 80, 4% sorbitol, 12% ethanol, 40% water) were characterized for droplet size, PDI, zeta potential, pH, and viscosity. Stability was evaluated by monitoring droplet size and PDI over time and by determining the retention of eugenol, methyl eugenol, and β-caryophyllene after storage at 45 °C. Fish anesthetic efficacy was tested in koi carp (Cyprinus carpio var. koi). Results: SNEDDS maintained a small droplet size (~22.78 ± 1.99 nm) and low PDI (0.188 ± 0.088 at day 60), while ME showed significant size enlargement (up to 177.10 ± 47.50 nm) and high PDI (>0.5). After 90 days at 45 °C, SNEDDS retained 94.45% eugenol, 94.08% methyl eugenol, and 88.55% β-caryophyllene, while ME preserved 104.76%, 103.53%, and 94.47%, respectively. In vivo testing showed that SNEDDS achieved faster anesthesia (114.70 ± 24.80 s at 120 ppm) and shorter recovery (379.60 ± 15.61 s) than ME (134.90 ± 4.70 s; 473.80 ± 16.94 s). Ethanol failed to induce anesthesia at 40 ppm and performed poorly compared to SNEDDS and ME at other concentrations (p < 0.0001). Conclusions: SNEDDS demonstrated superior physical stability and fish anesthetic performance compared to ME. These findings support SNEDDS as a promising formulation for delivering holy basil essential oil in biomedical and aquaculture applications. Full article

Oral delivery of hydrophobic compounds remains challenging due to their poor aqueous solubility and the potential toxicity associated with conventional surfactant-based emulsions. To address these issues, we present a surfactant-free encapsulation strategy using electrosprayed alginate hydrogel beads for the stable and controlled delivery of hydrophobic oils. Hydrophobic compounds were dispersed in high-viscosity alginate solutions without surfactants via ultrasonication, forming kinetically stable oil-in-water dispersions. These mixtures were electrosprayed into calcium chloride baths, yielding monodisperse hydrogel beads. Higher alginate concentrations improved droplet sphericity and suppressed phase separation by enhancing matrix viscosity. The resulting beads exhibited stimuli-responsive degradation and controlled release behavior in response to physiological ionic strength. Dense alginate networks delayed ion exchange and prolonged structural integrity, while elevated external ionic conditions triggered rapid disintegration and immediate payload release. This simple and scalable system offers a biocompatible platform for the oral delivery of lipophilic active compounds without the need for surfactants or complex fabrication steps. Full article

Poor solubility and bioavailability have limited the application of fucoxanthin in drug and functional food processing. In order to encapsulate fucoxanthin in delivery systems, in this study, cellulose was isolated from industrial brown algae residues and high-pressure homogenized into cellulose nanofibrils (CNFs). Then, fucoxanthin was encapsulated into the Pickering emulsion stabilized by the CNFs. The effect of high-pressure homogenization on the characteristics of cellulose and the stability of fucoxanthin emulsion was evaluated. The results indicated that CNFs prepared at 105 MPa had a diameter of 87 nm and exhibited high zeta potential and thermal stability. Encapsulation efficiency peaked at 70.8% with 1.0 mg/mL fucoxanthin, and after three freeze–thaw cycles the encapsulation efficiency was higher than 60%. The DPPH scavenging activity after 12 days’ storage at 4 °C was still 42%. Furthermore, the Pickering emulsion with 1.0 mg/mL fucoxanthin showed high stability and antioxidant activity under different pH values, salinity, temperature, and UV light exposure duration. The CNFs effectively protected fucoxanthin from degradation, offering a novel delivery system for marine bioactive compounds. To the best of our knowledge, this is the first study on the fucoxanthin delivery system of Pickering emulsion stabilized by the CNFs. Such emulsion might benefit the encapsulation and release of bioactive components in marine drugs. Full article

The rapid evolution of deep learning (DL) has fundamentally transformed the paradigm for detecting special components in agricultural products, addressing critical challenges in food safety, quality control, and precision agriculture. This comprehensive review systematically analyzes many seminal studies to evaluate cutting-edge DL applications across three core domains: contaminant surveillance (heavy metals, pesticides, and mycotoxins), nutritional component quantification (soluble solids, polyphenols, and pigments), and structural/biomarker assessment (disease symptoms, gel properties, and physiological traits). Emerging hybrid architectures—including attention-enhanced convolutional neural networks (CNNs) for lesion localization, wavelet-coupled autoencoders for spectral denoising, and multi-task learning frameworks for joint parameter prediction—demonstrate unprecedented accuracy in decoding complex agricultural matrices. Particularly noteworthy are sensor fusion strategies integrating hyperspectral imaging (HSI), Raman spectroscopy, and microwave detection with deep feature extraction, achieving industrial-grade performance ($RPD$ > 3.0) while reducing detection time by 30–100× versus conventional methods. Nevertheless, persistent barriers in the “black-box” nature of complex models, severe lack of standardized data and protocols, computational inefficiency, and poor field robustness hinder the reliable deployment and adoption of DL for detecting special components in agricultural products. This review provides an essential foundation and roadmap for future research to bridge the gap between laboratory DL models and their effective, trusted application in real-world agricultural settings. Full article

Peroxisome proliferator-activated receptor alpha (PPARα) is a key regulator of lipid metabolism, making its agonists valuable therapeutic targets for various diseases, including chronic peripheral neuropathy. Existing PPARα agonists face limitations such as poor selectivity, sub-optimal bioavailability, and safety concerns. We previously demonstrated that A190, a novel, potent, and selective PPARα agonist, effectively alleviates chemotherapy-induced peripheral neuropathy and CFA-induced inflammatory pain as a non-opioid therapeutic agent. However, A190 alone has solubility and permeability issues that limits its oral delivery. To overcome this challenge, in this study, four new-generation ester prodrugs of A190; A190-PD-9 (methyl ester), A190-PD-14 (ethyl ester), A190-PD-154 (isopropyl ester), and A190-PD-60 (cyclic carbonate) were synthesized and evaluated for their enzymatic bioconversion and chemical stability. The lead candidate, A190-PD-60, was further formulated as a microemulsion (A190-PD-60-ME) and optimized via Box–Behnken design. A190-PD-60-ME featured nano-sized droplets (~120 nm), low polydispersity (PDI < 0.3), and high drug loading (>90%) with significant improvement in artificial membrane permeability. Crucially, pharmacokinetic evaluation in rats demonstrated that A190-PD-60-ME reached a 16.6-fold higher Cmax (439 ng/mL) and a 5.9-fold increase in relative oral bioavailability compared with an A190-PD-60 dispersion. These findings support the combined prodrug-microemulsion approach as a promising strategy to overcome oral bioavailability challenges and advance PPARα-targeted therapies. Full article

Curcumin is widely recognized for its various pharmacological properties, including antioxidant, anti-inflammatory, and anti-tumor activities. Nevertheless, the development of curcumin as a therapeutic agent is impeded by its limited oral bioavailability, which stems from its chemical instability, poor aqueous solubility, and rapid degradation. This study aimed to develop granule formulations incorporating poly(N-isopropylacrylamide)-grafted hyaluronic acid or HA-g-pNIPAM to enhance dissolution and protect curcumin from degradation. Three formulations were developed: F10 (HA-g-pNIPAM physically mixed with curcumin), F10 Encap (curcumin encapsulated within HA-g-pNIPAM), and F11 (curcumin granules without HA-g-pNIPAM). The stability results showed that F10 Encap effectively maintained curcumin content throughout the study period, retaining approximately 94% of its initial concentration by day 30, compared to 70% from F11 (p < 0.05) at 30 °C and 75% relative humidity. All dried curcumin granules exhibited excellent flowability, as determined by the angle of repose measurements. All three formulations exhibited a consistent particle size distribution across replicates, with a peak in the 150–180 μm size range. The sustained release observed for F10 Encap and F10 after the initial burst suggested that the HA-g-pNIPAM provided a controlled release mechanism, ensuring continuous curcumin dissolution over 240 min in gastric and intestinal conditions. These findings suggested that HA-g-pNIPAM improved dissolution and stability of curcumin. Full article

Phytochemicals from medicinal plants offer significant therapeutic benefits, yet their clinical utility is often limited by poor solubility, instability, and low bioavailability. Nanotechnology presents a transformative approach to overcome these challenges by encapsulating phytochemicals in nanocarriers that enhance stability, targeted delivery, and controlled release. This review highlights major classes of phytochemicals such as polyphenols, flavonoids, and alkaloids and explores various nanocarrier systems including liposomes, polymeric nanoparticles, and hybrid platforms. It also discusses their mechanisms of action, improved pharmacokinetics, and disease-specific targeting. Further, the review examines clinical advancements, regulatory considerations, and emerging innovations such as smart nanocarriers, AI-driven formulation, and sustainable manufacturing. Nano-phytomedicine offers a promising path toward safer, more effective, and personalized therapies, bridging traditional herbal knowledge with modern biomedical technology. Full article

Poor aqueous solubility still disqualifies many promising drug candidates at late stages of development. Amorphous solid dispersion (ASD) technology solves this limitation by trapping the active pharmaceutical ingredient (API) in a high-energy, non-crystalline form, yet most marketed ASDs rely on synthetic carriers such as polyvinylpyrrolidone (PVP) and hydroxypropyl methylcellulose (HPMC), which raise concerns about long-term biocompatibility, residual solvent load, and sustainability. This study summarizes the emergence of natural polymer-based ASDs (NP-ASDs), along with the bond mechanism reactions through which these natural polymers enhance drug performance. As a result, NP-ASDs exhibit improved physical stability and significantly enhance the dissolution rate of poorly soluble drugs. The structural features of natural polymers play a critical role in stabilizing the amorphous state and modulating drug release profiles. These findings support the growing potential of NP-ASDs as sustainable and biocompatible alternatives to synthetic carriers in pharmaceutical development. Full article

Developing and utilizing capture and storage technologies for CO₂ has become a critical research topic due to the significant greenhouse effect caused by excessive CO₂ emissions. A conventional physical absorption process for CO₂ capture is polyethylene glycol dimethyl ether (NHD); however, its limited application range is caused by its poor absorption of CO₂ at low pressures. In this work, the CO₂ absorption of NHD was enhanced by combining NHD with a novel chemical absorbent 2-methylimidazole (2-mIm)-ethylene glycol (EG) solution to improve CO₂ absorption. Viscosity and CO₂ solubility were examined in various compositions. The CO₂ solubility in the mixed solution was found to be at maximum when the mass fractions of NHD, 2-mIm, and EG were 20%, 40%, and 40%, respectively. In comparison to pure NHD, the solubility of CO₂ in this mixed solution at 30 °C and 0.5 MPa increased by 161.2%, and the desorption heat was less than 30 kJ/mol. The complex solution exhibits high selectivity and favorable regeneration performance in the short term. However, it is more sensitive to moisture content. The results of this study can provide important data to support the construction of new low-energy solvent systems and the development of novel CO₂ capture processes. Full article

Background/Objectives: Curcumin is a promising therapy for glioblastoma but is limited by poor water solubility, rapid metabolism, and low blood–brain barrier penetration. This study aimed to evaluate curcumin and six curcumin derivatives with improved activity against a glioblastoma cell line and favorable absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties. Methods: Twenty-one curcumin derivatives were assessed and subjected to in vitro MTT cytotoxicity assays in SF268 glioblastoma and Vero cells. On the basis of the cytotoxicity results, six derivatives with the most favorable characteristics were selected for additional mechanistic studies, which included microtubule depolymerization, mitochondrial membrane potential (ΔΨm), and BAX activation assays. ADMET properties were determined in silico. Results: Compounds 2–4, 6, and 11 demonstrated better activity (IC₅₀: 0.59–3.97 µg/mL and SI: 3–20) than curcumin (IC₅₀: 6.3 µg/mL; SI: 2.5). Lead derivatives destabilized microtubules, induced ΔΨm collapse, and activated BAX. In silico ADMET prediction analysis revealed that compounds 4 and 6 were the most promising for oral administration from a biopharmaceutical and pharmacokinetic point of view. Conclusions: Strategic modifications were made to one or both hydroxyl groups of the aromatic rings of curcumin to increase its physicochemical stability and activity against glioblastoma cell line SF268. Compound 4, bearing fully protected aromatic domains, was identified as a prime candidate for in vivo validation and formulation development. Full article

Background: Blackberry seed oil (BSO), obtained from Rubus spp. Xavante cultivar via supercritical CO₂ extraction, contains bioactive lipids and antioxidants, but its cosmetic application is limited by poor solubility and stability. Nanoencapsulation with poly(ε-caprolactone) (PCL) can overcome these limitations. Methods: BSO was characterized by Ultra-High-Performance Liquid Chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry and incorporated into PCL nanocapsules (NCBSO) using the preformed polymer deposition method. Physicochemical properties, stability (at 4 °C, room temperature, and 37 °C for 90 days), cytotoxicity, and collagen production were assessed in human fibroblasts. Additionally, a predictive in silico analysis using PASS Online, Molinspiration, and SEA platforms was performed to identify the bioactivities of major BSO compounds related to collagen synthesis, antioxidant potential, and anti-aging effects. Results: NCBSO showed a nanometric size of ~267 nm, low polydispersity (PDI < 0.2), negative zeta potential (−28 mV), and spherical morphology confirmed by FE-SEM. The dispersion remained stable across all tested temperatures, preserving pH and colloidal properties. In particular, BSO and NCBSO at 100 µg.mL⁻¹ significantly enhanced in vitro collagen production by 170% and 200%, respectively, compared to untreated cells (p < 0.01). Superior bioactivity was observed for NCBSO. The in silico results support the role of key compounds in promoting collagen biosynthesis and protecting skin structure. No cytotoxic effects were achieved. Conclusions: The nanoencapsulation of BSO into PCL nanocapsules ensured formulation stability and potentiated collagen production. These findings support the potential of NCBSO as a promising candidate for future development as a collagen-boosting cosmeceutical. Full article

Safflower (Carthamus tinctorius L.) seeds, rich in triacylglycerols, have poor fatty acid-to-sugar conversion during storage, affecting longevity and vigor. Previous experiments have shown that the aging of safflower seeds is mainly related to the impairment of energy metabolism pathways such as glycolysis, fatty acid degradation, and the tricarboxylic acid cycle. The treatment with exogenous sucrose can partially promote the germination of aged seeds. However, the specific pathways through which exogenous sucrose promotes the germination of aged safflower seeds have not yet been elucidated. This study aimed to explore the molecular mechanism by which exogenous sucrose enhances the vitality of aged seeds. Phenotypically, it promoted germination and seedling establishment in CDT-aged seeds but not in unaged ones. Biochemical analyses revealed increased soluble sugars and fatty acids in aged seeds with sucrose treatment. Enzyme activity and transcriptome sequencing showed up-regulation of key enzymes and genes in related metabolic pathways in aged seeds, not in unaged ones. qPCR confirmed up-regulation of genes for triacylglycerol and fatty acid-to-sugar conversion. Transmission electron microscopy showed a stronger connection between the glyoxylate recycler and oil bodies, accelerating oil body degradation. In conclusion, our research shows that exogenous sucrose promotes aged safflower seed germination by facilitating triacylglycerol hydrolysis, fatty acid conversion, and glycometabolism, rather than simply serving as a source of energy to supplement the energy deficiency of aged seeds. These findings offer practical insights for aged seeds, especially offering an effective solution to the aging problem of seeds with high oil content. Full article