Search Results (2,378)

Background/Objectives: Poor aqueous solubility and low bioavailability limit the therapeutic use of many hydrophobic anticancer agents. This study developed liposomal and polymeric micellar formulations of a fluorinated curcumin derivative (FCur) and naringenin (NG), prepared as single-compound and mixed systems, and compared their physicochemical and biological properties. Methods: Soluplus^®-based polymeric micelles and POPC:DOTAP liposomes were prepared by the thin-film hydration method and characterised using dynamic light scattering (DLS), zeta potential measurements, HPLC, NMR relaxation studies, and in vitro cytotoxicity assays. Results: Polymeric micelles formed homogeneous dispersions with particle sizes below 95 nm and a slightly negative zeta potential (~−3 mV), whereas liposomes were larger (>130 nm) and strongly positively charged (>+40 mV). Both systems achieved high encapsulation efficiencies (>72% for FCur and >95% for NG). NMR relaxation studies revealed more restricted molecular dynamics within liposomal bilayers and greater motional freedom in micelles. In biological studies, FCur and mixed liposomes exhibited the highest overall cytotoxicity against bladder (5637), prostate (LNCaP) cancer as well as normal fibroblast (MRC-5) cell lines, compared with the free compounds and polymeric micelles. Notably, polymeric micelles with FCur (single and mixed) exhibited a more favourable differential cytotoxicity response between bladder cancer and normal cells. Conclusions: These findings demonstrate that the nanocarrier system plays a critical role in determining both molecular dynamics and biological performance of encapsulated agents. Full article

Biosurfactants are sustainable alternatives to petroleum-derived surfactants, yet their industrial application is often constrained by production costs and process efficiency. This study aimed to evaluate biosurfactant production by the psychrotolerant Antarctic bacterium Streptomyces luridus So3.2 using low-cost recycled frying oils under mild cultivation conditions and to validate the process in stirred-tank bioreactors. Cultivation conditions were optimized using response surface methodology (RSM), and the same optimized pH and carbon source concentration were subsequently applied in stirred-tank reactors at laboratory scales of 2 L and 20 L, while aeration (0, 0.5 and 0.9 vvm) and agitation speed (100, 150, and 200 rpm) were evaluated as reactor-operational variables. Filtered and centrifuged recycled frying oil yielded the highest biosurfactant performance (emulsification indices exceeding 80%, enhanced oil displacement, and surface tension values below 40 mN m⁻¹) compared to commercial oils. Biosurfactant production was growth-associated, with detectable surface activity within the first 24 h. RSM identified optimal cultivation parameters at pH 8.0, 3% (w/v) inoculum, and 2% (w/v) oil concentration. The biosurfactant exhibited a critical micelle concentration (CMC) of 29 mg L⁻¹ and a critical micelle dilution (CMD) of 43.2, yielding an estimated broth concentration of 1.25 g L⁻¹. At the 2 L reactor scale, moderate aeration (0.5 vvm) combined with intermediate agitation (150 rpm) preserved high surface activity, yielding emulsification indices above 83%, oil displacement halos of 12.5 cm, and surface tension values as low as 35.5 mN m⁻¹. This performance was also maintained during validation at 20 L. FTIR and TLC analyses indicated lipid- and peptide-associated functional groups. These findings were further complemented by HPLC, MALDI-TOF MS and genome-mining analyses (antiSMASH), revealing a complex molecular profile and multiple NRPS/NRPS-like biosynthetic gene clusters, supporting the interpretation of the recovered product as a putative lipopeptide-associated surface-active extract. Overall, this work demonstrates the feasibility of producing a biosurfactant-associated surface-active extract from recycled frying oils using S. luridus So3.2 under mild conditions. Full article

Camel milk (CM), which is produced by both Camelus dromedarius and Camelus bactrianus, is gaining increasing popularity as a value-added functional dairy product, but the science of managing its shelf life has progressed more slowly than its commercial expansion. Unlike bovine milk, CM lacks β-lactoglobulin (β-LG), has a unique casein (CN) micelle structure with a high β-CN-to-αs1-CN ratio, and low κ-CN protein content, and contains an unusually rich bioactive protein fraction including lactoferrin (LF), immunoglobulin G (IgG), lysozyme (LZ), and peptidoglycan recognition protein (PGRP). These compositional characteristics imbue CM with both significant inherent antimicrobial benefits and place it at risk of processing weaknesses that do not have direct analogs in bovine dairy science. The review discusses three key areas of CM shelf life science that have not been sufficiently addressed in the published literature. The first relates to physicochemical mechanisms of deterioration, including lipid oxidation of polyunsaturated fatty acids (PUFA), destabilization of CN micelles in the structural absence of β-LG, and Maillard browning during thermal treatment and storage of powder. The second addresses the fate of bioactive proteins, with the majority being lactoferrin (LF), immunoglobulin G (Igs), and heavy chain-only antibodies (HCAbs), under both thermal and non-thermal processing conditions. The third looks at new non-thermal preservation methods, such as high-pressure processing (HPP), pulsed electric field (PEF), ultrasonication, ultraviolet irradiation, cold plasma, and electromagnetic (EM) field treatment, and functional packaging innovations, which contribute to longer shelf life. Of the non-thermal options examined, HPP at 200–400 MPa today provides the most mechanistically proven evidence for camel-specific microbial deactivation with satisfactory quality preservation. The latest primary CM research also indicates that processing with EMs in the 850 mT range can potentially be as effective as conventional pasteurization in microbial control and may be more effective than pasteurization in retaining desirable bioactive markers, although this result needs to be independently replicated before more responsible conclusions can be drawn. The review ends with four priority research gaps: standardized kinetic shelf life modeling frameworks, systematic characterization of bioactive protein stability under commercial processing conditions, life cycle assessment of preservation chains across the camel dairy supply continuum, and the urgent validation of camel-specific pasteurization adequacy indicators to replace bovine alkaline phosphatase, which remains active in CM after conventional high-temperature short-time (HTST) pasteurization. Full article

Microencapsulation has become an indispensable technique across various industries that require the controlled release and stability of bioactive agents. In this study, the encapsulation of cinnamon essential oil (CEO), known for its antibacterial and anti-inflammatory properties, was study to enable controlled release when applied to textile substrates. This procedure involves defining and examining several steps to establish a stable, scalable complex coacervation methodology. To form a stable microcapsule matrix, CEO was emulsified using a combination of surfactants (Span 80, Tween 20, and Sodium Dodecyl Sulfate). After forming micelles containing CEO, two biopolymers (chitosan and gum Arabic) were used at various proportions to form a microcapsule shell via a layer-by-layer approach. Advanced characterization techniques, such as spectrophotometry and laser scattering, were used to evaluate microcapsule stability, size, and release kinetics, as well as to assess potential antibacterial activity. The presence of oil-containing microcapsules was confirmed using fourier transform infrared (FTIR) spectroscopy and thermogravimetric analysis (TGA). The results demonstrate that Span 80 concentrations of 0.4 and 0.7 g/L provided the most stable encapsulation environment and enabled a controlled CEO release profile after being applied to cotton substrates. In addition, the influence of the fabric’s chemical characteristics was clearly illustrated in the drug delivery experiments. However, antibacterial efficacy was limited due to the low CEO concentration within the microcapsules, indicating the need for further optimization. These findings provide valuable insights into the broader application of essential oil encapsulation, particularly within the pharmaceutical, textile, and cosmetic sectors. Full article

Podophyllotoxin (PPT) inhibits tumors such as lung cancer and breast cancer. However, it has poor water solubility and causes gastrointestinal dysfunction and bone marrow suppression, which severely limit its clinical application. Based on the differential reactive oxygen species (ROS) levels between tumor microenvironments and normal tissues, we designed and constructed a ROS-responsive micelle delivery system, successfully fabricating blank micelles (M) and PPT-loaded micelles (M@PPT). Both micelles exhibited good particle size uniformity, colloidal stability, and biosafety. The ROS responsiveness experiment revealed that, after incubating blank micelles (M) with 10 mM H₂O₂, the particle size increased significantly, and the size distribution broadened. High-performance liquid chromatography (HPLC) confirmed the release of cinnamaldehyde from the micelles upon H₂O₂ exposure. Additionally, DCFH-DA assays demonstrated that treatment with blank micelles (M) enhanced intracellular ROS levels. In vitro release studies showed that drug-loaded micelles (M@PPT) achieved 77.76% cumulative PPT release within 24 h in a buffer containing 10 mM H₂O₂, significantly exceeding the release observed in the H₂O₂-free control group. These results collectively validate the ROS-responsive disintegration of micelles and the subsequent release of cinnamaldehyde. The liberated cinnamaldehyde further amplified intracellular ROS levels, establishing a positive feedback loop that accelerated drug release. Cellular assays revealed superior tumor growth inhibition by M@PPT over free PPT, mediated through apoptosis induction, G2/M phase cell cycle arrest, downregulation of the anti-apoptotic protein Survivin, and upregulation of the p21 protein. In vivo studies further confirmed the enhanced antitumor efficacy and improved biosafety of M@PPT compared to free PPT. This ROS-responsive micellar system, by enabling tumor-targeted drug delivery and controlled release, provides a novel strategy to optimize the clinical utility of podophyllotoxin-based chemotherapeutics. Full article

Encapsulation of resveratrol (RVT), a natural polyphenol, in mixed Pluronic F127/P123 micelles (mRVT) has enhanced its pharmacological efficacy in experimental dementia models. The aim of this study was to evaluate neurochemical and behavioral parameters of mRVT treatment in healthy subjects. For this purpose, pure RVT and mRVT (both at 10 mg/kg i.p.) were applied for 9 consecutive days in healthy male Wistar rats. Memory performance was assessed using the novel object recognition and passive avoidance tests. Neurotransmitter levels, neurotrophic and transcription factors, and oxidative stress markers were quantified in the cortex and hippocampus using enzyme-linked immunosorbent assay kits. Our results showed that neither treatment altered locomotor activity or short-term memory performance. Both RVT and mRVT treatments reduced hippocampal acetylcholinesterase activity to a similar extent and elevated acetylcholine levels in the cortex and hippocampus, with mRVT producing significantly more pronounced effect in the hippocampus. Compared to pure RVT, mRVT elicited a greater increase in noradrenaline and serotonin levels in both brain regions and comparably upregulated BDNF and pCREB protein levels in the cortex. Furthermore, mRVT uniquely reduced cortical lipid peroxidation—an effect absent with pure RVT treatment. These findings demonstrate that micellar encapsulation substantially amplifies the neurochemical efficacy of resveratrol under physiological conditions without adverse behavioral effects. Full article

Autonomous and interconnected multiscale out-of-equilibrium processes, including chemical and physical feedbacks, occur at the micron and lower scales during the heterotrophic synthesis of simple abiotic protocells, such as the ones developed in our group, with primitive life-like properties. These processes provide a solution to the autopoiesis and concentration problems in life’s origin. They also underlie the emergence of whole-vesicle functionalities like chemotaxis and self-reproduction involving dissipation and degradation which are integrated into our life-like abiotic systems. Such abiotic systems can be considered simple examples in the ontological classification of “life beyond biochemistry” (LBB), as they are based on carbon chemistry and, by design, do not use any biochemical compounds to integrate the basic system-level properties of natural life. This contribution analyzes a class of highly-out-of-equilibrium LBB systems we call “phoenix” and connects degradation pathways due to the presence of oxygenic species to enabling basic functionalities in these simple life beyond biochemistry systems such as protocell self-reproduction and the mechano-chemical squirting out into the medium of a fraction of their partially reacted lumen that enables heritable variation in our systems. We conclude that degradation within the lumen of mature micelles turning into vesicles may also be considered as a driving force for chemical evolution due to the number of new proximate reaction pathways it can open up. Full article

Inflammation and oxidative stress induced by high glucose levels constitute essential factors impeding wound healing in diabetes, posing a significant threat to public health. Despite its notable anti-inflammatory and antioxidant potential, the clinical applicability of quercetin is hampered by its hydrophobicity and limited oral bioavailability. To address these issues, the thin-film hydration method was used to encapsulate quercetin into FQ micelles. Subsequently, 3-aminophenylboronic acid-modified oxidized alginate was crosslinked with polyvinyl alcohol, and simultaneously loaded with glucose oxidase (GOX) and FQ micelles, to construct a glucose-activated cascade acidification-triggered controlled-release hydrogel (OSSP@FQ&GOX). The phenylboronic ester bonds in the hydrogel are responsive to glucose and undergo cleavage. GOX-mediated oxidation of glucose produces gluconic acid, resulting in a lower local pH and subsequently triggering FQ micelle release. The released FQ micelles alleviate oxidative stress and exert immunomodulatory effects, while the hydrogel also provides self-healing, and biocompatible properties that facilitate cutaneous regeneration in diabetic mice. Thus, this study highlights the potential of combining GOX with natural products and multi-stimuli-responsive hydrogels for the treatment of chronic diabetic wounds, while also opening new avenues for the development of multifunctional wound dressings. Full article

Background: The highly heterogeneous and dynamically evolving tumor microenvironment leads to the development of drug resistance and recurrence in traditional therapies. Although immunotherapy demonstrates unique advantages, its clinical utility remains constrained by the suboptimal immunogenicity and the limited effect of monotherapy. Herein, a hybrid drug delivery system based on a spatiotemporal hierarchical controlled-release strategy was proposed to achieve dual immunotherapy with immune checkpoint blockade (ICB) and immunogenic cell death (ICD) to promote synergistic anti-tumor therapy. Methods: A liposome–micelle hybrid drug delivery system (RUT-RPP-LP) was constructed using a lipid bilayer composed of dioleoyl phosphatidylethanolamine/hemisuccinyl cholesterol to encapsulate rutin (RUT) and to form an inner cavity-encapsulated resveratrol micelle (RPP). RUT-RPP-LP was characterized, and its pH sensitivity and release behavior were investigated. Subsequently, a colon cancer tumor-bearing mouse model was constructed to evaluate the in vivo targeted anti-tumor effect and biological safety. On this basis, the combined mechanism of ICB and ICD was preliminarily explored. Results: RUT-RPP-LP possessed excellent formulation characteristics, stability, and biocompatibility, achieving graded controlled release of drugs via responding to the TME and lysosomal acidity, respectively. Obviously, RUT-RPP-LP could specifically target the tumor site, induce the occurrence of ICD, and simultaneously block the PD-1/PD-L1 immune checkpoint signaling pathway, thereby enhancing the function of T cells and inducing apoptosis of tumor cells. Conclusions: The RUT-RPP-LP based on the hierarchical controlled-release strategy exerted a spatiotemporally coordinated enhancement of anti-tumor immunity, and may provide a novel combinatorial approach to overcome the low response of immunotherapy in solid tumors. Full article

Wormlike micelles provide the structural basis for the viscoelasticity of clean fracturing fluids, yet the molecular mechanism by which calcium-containing brine regulates their growth remains insufficiently understood. In this work, all-atom molecular dynamics simulations were performed to investigate the calcium-regulated self-assembly of an EAHSB/EHAC/NaPts surfactant–counterion system. In the absence of Ca²⁺, dispersed surfactant and counterion molecules first formed small spherical aggregates, which subsequently fused into larger micelles, rod-like intermediates, and finally wormlike micelles. Increasing the local surfactant/counterion loading further promoted one-dimensional micellar growth and network-like association. When Ca²⁺ was introduced, the assembly process became slower and the final aggregate morphology shifted from elongated wormlike micelles to smaller spherical aggregates. Radial distribution functions and coordination-number analysis show that Ca²⁺ redistributes charged-group correlations within the mixed surfactant/counterion assemblies. Hydration analysis indicates enlarged polar hydration shells, whereas hydrophobic-tail hydration and gauche-defect probabilities reveal enhanced tail exposure and looser chain packing. These results demonstrate that Ca²⁺ suppresses wormlike micelle growth through coupled electrostatic redistribution, interfacial hydration, and hydrophobic-chain disorder, thereby favoring high-curvature spherical aggregates over extended wormlike networks. Full article

Wet age-related macular degeneration (wAMD) is characterized by choroidal neovascularization (CNV) and remains a major cause of severe vision loss in older adults. Intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy is the current standard of care for wAMD. However, repeated injections are associated with poor adherence, procedure-related complications, and a substantial cumulative treatment burden. Topical nanocarrier-based systems have therefore attracted increasing attention as needle-free approaches for improving posterior segment drug exposure. Complementing broader reviews of ocular nanomedicine, this review specifically examines topical nanocarrier-mediated posterior segment delivery for wAMD, with a focus on three representative platforms: liposomes, polymeric nanoparticles, and polymeric micelles. These systems are engineered through the optimization of particle size, surface properties, drug-loading strategies, and functional modifications to improve payload stability, ocular surface residence, tissue penetration, and lesion-relevant delivery. By integrating formulation design, ocular barrier transport, ocular posterior segment bioavailability, and translational feasibility in the context of wAMD, this review provides a disease-focused and application-oriented perspective that complements existing broader reviews of ocular nanocarriers and ophthalmic nanomedicine. We summarize current evidence from preclinical and translational studies and discuss major barriers limiting clinical application, including insufficient posterior segment drug exposure, dose–safety trade-offs, pharmacokinetic instability, limited targeting efficiency, and challenges in delivering macromolecular biologics, such as anti-VEGF antibodies and fusion proteins. At present, topical nanocarrier-based strategies remain investigational, but they hold potential for development as therapeutic approaches for wAMD. Key priorities for future development include quantitative posterior segment pharmacokinetic/pharmacodynamic evaluation, long-term safety assessment, payload-specific carrier design, scalable manufacturing, and clinically relevant efficacy endpoints. This review provides a focused framework for the rational design and translational assessment of nanocarrier-based topical strategies for wAMD management. Full article

The micellization behavior of binary mixtures of the nonionic surfactants Triton X-100 and Brij S20 was investigated in aqueous solution in the absence and presence of β-cyclodextrin (βCD) over the temperature range 283.15–318.15 K. Critical micelle concentrations (CMC) were determined and analyzed using regular solution theory to evaluate mixed micelle composition, interaction parameters, activity coefficients, and excess Gibbs free energies. The Triton X-100/Brij S20 system exhibited pronounced synergistic interactions, reflected by negative interaction parameters, reduced CMC values, and negative excess Gibbs free energies over the entire composition range. The addition of βCD systematically increased CMC values and reduced the magnitude of the interaction parameters, indicating that inclusion complex formation competes with micellization and weakens surfactant–surfactant interactions. Corrected micellar compositions revealed significant redistribution of surfactants between the aqueous phase and mixed micelles due to host–guest complexation. Thermodynamic analysis demonstrated spontaneous formation of βCD inclusion complexes with both surfactants, characterized by negative Gibbs free energy, enthalpy, and entropy changes. Triton X-100 exhibited a higher affinity toward βCD than Brij S20. The results demonstrate that coupled equilibria between micellization and inclusion complex formation govern the behavior of the system and suggest that conformational contributions should be considered when interpreting interaction parameters in cyclodextrin–surfactant systems. Full article

A novel centrifuge-less cloud-point extraction (CL-CPE) method based on pyrogallol (PG) was developed for the spectrophotometric determination of total vanadium. The method employs a mixed micelle-mediated extraction system comprising the nonionic surfactant Triton X-114 and the ionic liquid Aliquat 336 (A336), which serves as a source of monovalent cations capable of forming an ion pair with the anionic vanadium–PG chelate. The extracted species, (A336⁺)[V^IV(OH)(PG)₂], exhibits several absorption maxima (309, 362, and 436 nm), providing enhanced selectivity through appropriate wavelength selection according to the sample matrix. The principal absorption maximum occurs at 309 nm. At a sevenfold preconcentration factor, the method provides high sensitivity at this wavelength, with a molar absorptivity of 3.2 × 10⁷ L mol⁻¹ cm⁻¹, a limit of detection of 0.11 ng mL⁻¹, and a Sandell sensitivity of 1.6 × 10⁻³ ng cm⁻². The applicability of the method was demonstrated through the analysis of drinking water samples, spent vanadium catalyst materials, and vanadium-containing dietary supplements. The method was further evaluated using the RGBfast model, a white analytical chemistry assessment tool that integrates analytical performance, environmental sustainability, and practical and economic efficiency. The evaluation indicated a high overall whiteness score. Full article

Cancers still remain one of the most significant challenges in medicine or pharmacy, accounting for nearly 10 million deaths annually and imposing a substantial socioeconomic burden worldwide. Although chemotherapy continues to play a central role in the treatment of many tumors, conventional anticancer therapies are frequently associated with poor selectivity, systemic toxicity, multidrug resistance, and unfavorable pharmacokinetic profiles. Paclitaxel (PTX), one of the most widely used antineoplastic agents, demonstrates remarkable clinical efficacy against breast, ovarian, lung, pancreatic, and several other malignancies. Nevertheless, its clinical application remains limited by poor aqueous solubility, non-specific biodistribution, dose-limiting toxicities, and the development of resistance mechanisms. Nanotechnology-based anticancer drug delivery systems have emerged as a promising strategy to address these limitations. Among them, polymeric nanosystems have attracted particular attention owing to their physicochemical properties, biocompatibility, controlled drug-release capabilities, and potential for tumor-targeted delivery. Natural, semi-synthetic, and synthetic polymers are extensively investigated as carriers for PTX, leading to the development of nanoparticles, micelles, nanogels, nanofibers, dendritic systems, and hybrid nanoplatforms. Nanosystems demonstrate enhanced therapeutic efficacy, reduced systemic toxicity, prolonged circulation times, and improved tumor accumulation in preclinical models. Despite encouraging laboratory results, the clinical translation of polymeric PTX nanocarriers (NCs) remains limited. Numerous barriers, including tumor heterogeneity, variability of the enhanced permeability and retention (EPR) effect, manufacturing complexity, regulatory challenges, scale-up difficulties, and discrepancies between animal models and human cancers, continue to hinder successful commercialization and widespread clinical adoption. This review critically discusses the current state of polymeric drug delivery systems (DDSs) that contain PTX, as well as the advantages and limitations of synthetic, natural, and semi-synthetic polymers used in DDS technologies. Furthermore, translational challenges and future perspectives of PTX-based DDSs were analyzed. Full article

The skin is the largest organ of the human body and acts as a major protective barrier against external agents. However, the highly organized stratum corneum limits the effective delivery of many therapeutic compounds, especially hydrophilic and high-molecular-weight drugs. Conventional topical formulations often exhibit poor permeability, low bioavailability, and limited targeting efficiency. This review discusses recent advances in nanotechnology-based drug delivery systems, including bio-based, biodegradable, and biocompatible polymeric nanocarriers for dermal and transdermal applications, with particular emphasis on vesicular, polymeric, and hybrid nanosystems. Nanocarriers such as liposomes, ethosomes, transfersomes, polymeric nanoparticles, micelles, nanogels, and lipid–polymer hybrid systems have demonstrated improved drug solubility, stability, controlled release, and skin permeation for localized (dermal) delivery compared with conventional formulations. In addition, biodegradable polymeric materials enhance dermal deposition and prolong drug retention, leading to improved therapeutic efficacy. These nanosystems can facilitate enhanced transdermal drug transport under optimized conditions; however, the extent of systemic delivery varies widely depending on drug physicochemical properties, formulation characteristics, and application conditions. Drug transport may occur through intercellular, transcellular, and follicular pathways, resulting in enhanced bioavailability and site-specific delivery. Claims regarding transdermal (systemic) absorption are restricted to cases supported by in vivo or clinical evidence. Furthermore, combining nanocarriers with microneedles and stimuli-responsive platforms has expanded the potential for controlled and on-demand transdermal delivery. Recent preclinical and clinical studies have reported that nanocarrier-based methotrexate gels reduced PASI-like scores by over 70% in psoriatic models, while oleic acid vesicle formulations achieved more than 95% cure rates in rodent models of tinea corporis. Despite these advances, challenges related to large-scale production, stability, regulatory approval, and clinical translation remain significant. Future developments integrating smart nanocarriers, bio-based polymeric biomaterials, wearable technologies, and AI-assisted design may improve personalized dermatological therapies. These innovations in nanocarrier drug delivery are accelerating the translation of advanced therapies to the clinic, promising safer, more effective and personalized dermatological treatments. Full article