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18 pages, 1772 KB  
Article
Enhanced Electrochemiluminescence by Nanocatalyst-Supported Nanochannel–Surfactant Micelle Assembly for Ultrasensitive Detection of Rifampicin
by Jiahui Lin, Zhongping Mao and Fei Yan
Biosensors 2026, 16(5), 236; https://doi.org/10.3390/bios16050236 - 23 Apr 2026
Viewed by 98
Abstract
Developing an ultrasensitive electrochemiluminescence (ECL) detection platform remains challenging due to the limited enrichment efficiency of ECL emitters and co-reactants at the electrode interface, as well as the insufficient catalytic enhancement of co-reactant conversion. Moreover, simultaneous in situ analyte enrichment and efficient anti-interference [...] Read more.
Developing an ultrasensitive electrochemiluminescence (ECL) detection platform remains challenging due to the limited enrichment efficiency of ECL emitters and co-reactants at the electrode interface, as well as the insufficient catalytic enhancement of co-reactant conversion. Moreover, simultaneous in situ analyte enrichment and efficient anti-interference capability are often difficult to achieve in a single sensing interface. Herein, a new ECL platform was developed based on nanocatalyst-supported nanochannel-confined surfactant micelle (SM) system, which integrates an enhanced luminol-dissolved oxygen (DO) ECL response for the ultrasensitive detection of antibiotic rifampicin (RIF). A nanocomposite comprising nitrogen-doped graphene quantum dots and a molybdenum disulfide nanosheet (NGQDs@MoS2) was modified on an indium tin oxide (ITO) electrode. This nanocomposite layer catalyzed the oxygen reduction reaction (ORR), boosting the co-reactant efficiency of DO. Vertically ordered mesoporous silica film filled with surfactant micelles (SM@VMSF) was subsequently grown in situ on the NGQDs@MoS2 surface. The hydrophobic micelles enable the simultaneous enrichment of luminol, DO, and RIF. Integrating the triple-enrichment effect of surfactant micelles with the high electrocatalytic effect of NGQDs@MoS2 nanocomposite results in significant ECL enhancement of the luminol–DO. SM@VMSF also provides an excellent molecular sieving effect, endowing the sensor with high anti-interference capability and stability. RIF quenches the ECL signal by consuming superoxide anion radicals, enabling sensitive detection. Detection of RIF was established with a high sensitivity (2927 a.u. per nM) wide linear range (10 pM to 10 μM) and a low limit of detection (LOD, 2.5 pM). The fabricated sensor exhibits good selectivity and high fabrication reproducibility (relative standard deviation, RSD, of 1.9%). Additionally, the determination of RIF in eye drops and seawater samples was realized. This work offers new insights for the design of high-performance ECL sensing interfaces and sensitive detection of RIF. Full article
(This article belongs to the Special Issue Recent Developments in Nanomaterial-Based Electrochemical Biosensors)
40 pages, 2666 KB  
Perspective
Borate-Bridged Protolipids: A Prebiotic Route to Abiotic Membranes
by Valery M. Dembitsky, Alexander O. Terent’ev and Ion Romulus I. Scorei
Life 2026, 16(5), 714; https://doi.org/10.3390/life16050714 - 22 Apr 2026
Viewed by 230
Abstract
The emergence of membrane boundaries represents a decisive transition in the origin of life, yet the molecular nature of the earliest abiotic membranes remains uncertain. Existing models based on simple fatty acids, while experimentally tractable, often lack the environmental robustness required under fluctuating [...] Read more.
The emergence of membrane boundaries represents a decisive transition in the origin of life, yet the molecular nature of the earliest abiotic membranes remains uncertain. Existing models based on simple fatty acids, while experimentally tractable, often lack the environmental robustness required under fluctuating prebiotic conditions. Furthermore, the absence of clear pathways linking primitive amphiphiles to later phospholipid systems highlights the need for chemically continuous intermediate frameworks. Here, we explore borate-bridged amphiphile–carbohydrate conjugates as plausible intermediates between simple prebiotic surfactants and modern lipid bilayers. These conjugates arise from low-molecular-weight polyols—including glycerol, butane-1,2,3,4-tetraol, pentane-1,2,3,4,5-pentaol, and hexane-1,2,3,4,5,6-hexitol—reacting with long-chain alkyl ethers and borate species under alkaline conditions, enabling reversible coupling to ribose and other vicinal diol-containing sugars. This chemistry integrates three essential properties for early compartmentalization: hydrolytically robust ether-linked hydrophobic domains, multivalent and highly hydrated headgroups, and environmentally responsive borate coordination. Comparative physicochemical analysis suggests that single-tail alkylglycerol derivatives preferentially form micelles and interfacial films, while di- and tri-tail tetritol and pentitol conjugates favor lamellar assemblies and vesicle formation across realistic prebiotic pH and salinity ranges. Hexitol-based systems, particularly those bearing three hydrophobic chains, may act as membrane-stabilizing components that enhance rigidity and reduce permeability under extreme conditions. We propose that heterogeneous mixtures dominated by two-tail polyol diethers, supplemented by tri-tail stabilizers and surface-active alkylglycerols, could provide mechanically robust, pH-tunable, and sugar-decorated abiotic membranes. Such borate-mediated amphiphiles offer a chemically coherent framework linking carbohydrate stabilization, ether lipid persistence, and dynamic self-assembly, potentially representing a transitional stage in the evolutionary pathway from primitive amphiphilic films to biologically encoded membranes. Full article
(This article belongs to the Special Issue Recent Trends in Prebiotic Chemistry)
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21 pages, 1890 KB  
Article
Sodium Stearate-Assisted Optimization of a Cannabidiol Dry Powder Inhaler for Enhanced Dissolution and Aerosol Performance
by Jin-Hyuk Jeong, Jae Seok Jeong, Hyeon-Seo Moon, Jae Woon Son, Kyung Hyun Min, Dong-Wook Kim, Chang-Soo Han, Wonwoong Lee, Chun-Woong Park and Ji-Hyun Kang
Pharmaceutics 2026, 18(4), 512; https://doi.org/10.3390/pharmaceutics18040512 - 21 Apr 2026
Viewed by 344
Abstract
Background/Objectives: Cannabidiol (CBD) has emerged as a potential therapeutic agent for respiratory disorders, including asthma and chronic obstructive pulmonary disease. However, its clinical translation via pulmonary delivery is limited by poor aqueous solubility, chemical instability, and low local bioavailability. This study aimed [...] Read more.
Background/Objectives: Cannabidiol (CBD) has emerged as a potential therapeutic agent for respiratory disorders, including asthma and chronic obstructive pulmonary disease. However, its clinical translation via pulmonary delivery is limited by poor aqueous solubility, chemical instability, and low local bioavailability. This study aimed to develop and optimize a sodium stearate (NaSt)-based spray-dried dry powder inhaler (DPI) formulation to enhance the aerosol performance, dissolution, and storage stability of CBD. Methods: CBD microparticles were prepared by spray drying using NaSt as the primary excipient. The feed preparation method, spray-drying parameters, and CBD:NaSt ratios were systematically optimized. The resulting powders were evaluated for aerodynamic properties using cascade impaction, dissolution behavior in simulated lung fluid, solid-state characteristics, and accelerated stability under stress conditions. Results: The optimized formulation, SD-4, a spray-dried CBD:NaSt formulation prepared at a 20:80 weight ratio using Process B, demonstrated excellent aerosolization performance, with a fine particle fraction (FPF) exceeding 50% and a mass median aerodynamic diameter (MMAD) of 5.08 ± 0.1 μm. Dissolution testing revealed more than a three-fold increase in drug release compared with raw CBD, attributed to amorphous dispersion within the NaSt matrix and surfactant-induced micellization. Accelerated stability studies confirmed improved retention of the amorphous state and drug content, while antioxidant incorporation further reduced oxidative degradation. Conclusions: The NaSt-based spray-dried formulation significantly improved aerosol deposition efficiency, dissolution rate, and physicochemical stability of CBD. This formulation strategy may provide a promising platform for pulmonary delivery of poorly water-soluble compounds. Full article
(This article belongs to the Special Issue Microparticle Platforms for Respiratory Delivery)
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25 pages, 3562 KB  
Article
A Novel Ocellatin-P1 Isoform from Leptodactylus labyrinthicus Frog Skin Secretion: Purification, Biological Properties and Three-Dimensional Structure
by César Augusto Prías-Márquez, Eliane Santana Fernandes Alves, Carlos José Correia de Santana, Osmindo Rodrigues Pires Júnior, Eduardo Maffud Cilli, Fabiano José Queiroz Costa, Alice da Cunha Morales Álvares, Sonia Maria de Freitas, Isabel de Fátima Correia Batista, Rafael Marques Porto, Isabelle S. Luz, Ricardo B. Azevedo, João Paulo Stawiarski Miranda, Henrique de Oliveira Noronha, Marco Antônio Damasceno Faustino, Felipe da Silva Mendonca de Melo, Alexandra Maria dos Santos Carvalho, Izabela Marques Dourado Bastos, Wagner Fontes, Aline L. Oliveira, Luciano M. Lião and Mariana S. Castroadd Show full author list remove Hide full author list
Int. J. Mol. Sci. 2026, 27(8), 3658; https://doi.org/10.3390/ijms27083658 - 20 Apr 2026
Viewed by 235
Abstract
A novel ocellatin-P1 isoform was isolated and purified from the skin secretion of the pepper frog Leptodactylus labyrinthicus. The crude skin secretion was fractionated by reversed-phase high-performance liquid chromatography (RP-HPLC) using a C8 column and the peptide was subsequently purified on [...] Read more.
A novel ocellatin-P1 isoform was isolated and purified from the skin secretion of the pepper frog Leptodactylus labyrinthicus. The crude skin secretion was fractionated by reversed-phase high-performance liquid chromatography (RP-HPLC) using a C8 column and the peptide was subsequently purified on a reversed-phase C18 column. Ocellatin-LB3 (as this isoform was named) was chemically sequenced by Edman degradation. This peptide is a linear C-terminally amidated molecule composed of 25 amino acid residues: 1GLLDTLKGAAKNVVGGLASKVMEKL25-NH2. Synthetic ocellatin-LB3 was active against Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa and inactive against Staphylococcus aureus, Staphylococcus epidermidis and Enterococcus faecalis. In addition, the peptide reduced the Trypanosoma cruzi infection in L6 cells. At 64 µM it did not reduce erythrocytes or polymorphonuclear leukocytes, but did reduce mononuclear leukocyte counts, as detected by flow cytometry. No hemolytic activity was observed in red blood cells even at 128 µM. The peptide exhibited limited antiproliferative activity against MCF-7 and HeLa tumor cells at 128 µM. Pre-incubation with the peptide appeared to enhance N-formylmethionine-leucyl-phenylalanine (fMLP)-induced migration, indicating a potential additive or synergistic effect on human neutrophils. The three-dimensional structure of ocellatin-LB3 was investigated by circular dichroism (CD) and nuclear magnetic resonance (NMR). In the presence of sodium dodecyl sulfate (SDS), the peptide adopts an α-helical structure spanning residues Leu3–Lys24, which remains largely preserved even at 95 °C. NMR Hydrogen/Deuterium (H/D) exchange experiments suggest that ocellatin-LB3 adopts a preferential orientation when interacting with SDS micelles. Based on the similarity among ocellatins, and on the physicochemical and structural properties of this peptide, a possible membrane-mediated mode of action is proposed, although this remains to be experimentally validated. Full article
(This article belongs to the Special Issue Animal‐Derived Bioactive Peptides as Next‐Generation Therapeutics)
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29 pages, 15834 KB  
Article
Ge11-Modified pH-Sensitive Polymer Micelles: A New Breakthrough in Targeted Therapy for Non-Small-Cell Lung Cancer
by Xingmeng Ma, Zhu Wang, Jingyi Wang, Xingyu Chen, Jinggang Zhang, Dengxue Yang, Shiyi Xu and Xueying Yan
Pharmaceutics 2026, 18(4), 498; https://doi.org/10.3390/pharmaceutics18040498 - 17 Apr 2026
Viewed by 182
Abstract
Background/Objective: In lung cancer treatment, increasing the concentration of antitumor drugs at the tumor site, enhancing efficacy, and reducing systemic toxicity are significant challenges. This study aims to develop an intelligent responsive polymer micelle system (GPDD) that achieves efficient accumulation and controlled [...] Read more.
Background/Objective: In lung cancer treatment, increasing the concentration of antitumor drugs at the tumor site, enhancing efficacy, and reducing systemic toxicity are significant challenges. This study aims to develop an intelligent responsive polymer micelle system (GPDD) that achieves efficient accumulation and controlled release of drugs at lung tumor sites through targeted and pH-responsive design. Methods: The GPDD system is formed by the self-assembly of GE11-PEG-hyd-DOX conjugates and co-loads free DOX. This system utilizes the targeting effect of the GE11 peptide with the epidermal growth factor receptor (EGFR) to accumulate at the tumor site, while the hydrazone bond serves as a pH-responsive linker that breaks in the acidic tumor microenvironment, triggering drug release. Experiments employed CCK-8 cytotoxicity assays and tumor-bearing nude mouse models (strain not specified) for in vitro and in vivo evaluations. Results: In vitro experiments showed that GE11-modified GPDD effectively inhibited tumor cell growth. In tumor-bearing nude mouse experiments, GPDD demonstrated more significant tumor suppression effects and lower systemic toxicity compared to free DOX and unmodified PDD. Conclusions: The GPDD nanocarrier integrates targeting and pH responsiveness, improving antitumor efficacy and reducing side effects, with translational potential. The novelty of the study lies in its dual-functional design and co-loading strategy, providing new insights for tumor-targeted delivery systems. Full article
(This article belongs to the Topic Advanced Nanocarriers for Targeted Drug and Gene Delivery)
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17 pages, 1444 KB  
Article
Characterization of the Biosurfactant Produced by Indigenous Bacteria from Mature Fine Tailings
by Shima Shojaei and Catherine N. Mulligan
Bioengineering 2026, 13(4), 452; https://doi.org/10.3390/bioengineering13040452 - 13 Apr 2026
Viewed by 593
Abstract
Biosurfactants offer a green, sustainable approach to many environmental bioremediations, especially for oil contamination. In this study, the aim is to evaluate the effectiveness of biosurfactants in accelerating hydrocarbon removal from mature fine tailings under anaerobic conditions. The bacteria were isolated from mature [...] Read more.
Biosurfactants offer a green, sustainable approach to many environmental bioremediations, especially for oil contamination. In this study, the aim is to evaluate the effectiveness of biosurfactants in accelerating hydrocarbon removal from mature fine tailings under anaerobic conditions. The bacteria were isolated from mature fine tailings and tested for biosurfactant production using different biosurfactant screening methods (i.e., blood agar, cetyltrimethylammonium bromide (CTAB) blue agar, oil displacement, and drop collapse). The most efficient strain showed high similarity to Stutzerimonas stutzeri by 16S rRNA gene sequencing. Results showed that this strain produces rhamnolipids with a critical micelle concentration (CMC) of 600 mg/L and a minimum surface tension of 38.70 ± 0.08 mN/m. Moreover, when supplemented with whey, the strain showed a high emulsification index of 24 toward toluene (66%) and hexane (60%). The bioremediation of mature fine tailings (MFTs) was conducted under anaerobic conditions by adding a consortium of the four strains that were positive in biosurfactant screening tests. The results showed 53% removal of n-alkane C9-C30 and a reduction in surface tension from 69 ± 0.5 mN/m to a minimum of 54.33 ± 0.5 mN/m. The results suggest the potential successful application of bioaugmentation for in situ biological treatment in the oil sands industry. Full article
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36 pages, 2671 KB  
Review
Cannabinoids for Dermatological Applications: Mechanistic Insights, Clinical Evidence, and Emerging Nanotechnology-Enabled Delivery Strategies
by Ashutosh Pareek, Lipika Kumari, Lance R. McMahon, Anil Chuturgoon and Aaushi Pareek
Pharmaceutics 2026, 18(4), 469; https://doi.org/10.3390/pharmaceutics18040469 - 12 Apr 2026
Viewed by 582
Abstract
Cannabinoids (CBs) derived from Cannabis sativa have attracted growing interest for dermatological applications due to their anti-inflammatory, antiproliferative, antimicrobial, antifibrotic, and antipruritic properties. However, their clinical translation is significantly limited by physicochemical and pharmacokinetic challenges, including poor aqueous solubility, lipophilicity, instability, variable skin [...] Read more.
Cannabinoids (CBs) derived from Cannabis sativa have attracted growing interest for dermatological applications due to their anti-inflammatory, antiproliferative, antimicrobial, antifibrotic, and antipruritic properties. However, their clinical translation is significantly limited by physicochemical and pharmacokinetic challenges, including poor aqueous solubility, lipophilicity, instability, variable skin penetration, and inconsistent bioavailability. At the molecular level, CBs modulate keratinocyte proliferation, sebocyte activity, fibroblast function, melanocyte balance, and immune signalling through CB1/CB2 receptors, TRP channels, and PPARγ pathways. Evidence supports their potential in the treatment of psoriasis, atopic dermatitis, acne, allergic contact dermatitis, pruritus, scleroderma, and skin cancers. Clinical evidence remains preliminary: topical and oral formulations have demonstrated anti-inflammatory, antiproliferative, antibacterial, and antifibrotic effects, with improvements in pruritus, lesion severity, and quality of life in early-phase studies. However, most trials are small, uncontrolled, and lack placebo comparators, limiting generalisability. To overcome formulation barriers and enhance dermal delivery, advanced pharmaceutical strategies such as liposomes, nanoemulsions, polymeric nanoparticles, micelles, and transdermal systems have been investigated to improve stability, controlled release, and targeted skin deposition while minimising systemic exposure. This review integrates mechanistic insights, clinical evidence, and emerging nanotechnology-enabled delivery approaches, emphasising rational formulation design and translational considerations necessary for advancing CBs toward standardised and clinically reliable dermatological therapeutics. Full article
(This article belongs to the Section Nanomedicine and Nanotechnology)
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21 pages, 1380 KB  
Article
Influence of Pulsed Electric Field Technology on Functionality and Protein Structure of Evaporated Skim Milk and Nonfat Dry Milk
by Elizabeth L. Ryan and Owen M. McDougal
Int. J. Mol. Sci. 2026, 27(8), 3395; https://doi.org/10.3390/ijms27083395 - 10 Apr 2026
Viewed by 374
Abstract
Nonfat dry milk (NFDM) powder was produced by spray drying a pulsed electric field (PEF)-treated solution of 48% (m/m) evaporated skim milk (ESM) that was treated with a field strength of 20 kV/cm and specific energy of 15 kJ/L at 150 L/h. PEF [...] Read more.
Nonfat dry milk (NFDM) powder was produced by spray drying a pulsed electric field (PEF)-treated solution of 48% (m/m) evaporated skim milk (ESM) that was treated with a field strength of 20 kV/cm and specific energy of 15 kJ/L at 150 L/h. PEF treatment induced reduction to particle size for whey proteins by 8.4% and casein micelles by 11.1% and increased conductivity by 10.6%. The PEF-treated ESM solution was less viscous than the non-PEF control (14.5% lower) and sedimentation was reduced by 40%. Increases to the tapped density (1.9%), solubility (4.7%), and emulsification stability (60%) of the NFDM were observed after PEF treatment. Evaluation of protein structure indicated no modification to the secondary structure, while minor changes to the tertiary structure were observed with increased fluorescence intensity and decreased transition temperatures. The reduction in casein micelle size for the PEF-treated ESM may be associated with the movement of minerals to the aqueous solvent. This study is the first to apply PEF technology to a highly concentrated ESM solution using a continuous flow commercial PEF system. The results of this study suggest that PEF technology may be beneficial to improving the dairy processing efficiency of ESM and product quality for NFDM. Full article
(This article belongs to the Special Issue Biophysical Studies of Protein Structure-Function Relationships)
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32 pages, 7395 KB  
Article
A Dual-Drug Nanocarrier Strategy for Ocular Fungal Infections: Micelles Embedded in Electrospun Nanofibers
by Egemen Uzel, Meltem Ezgi Durgun, Neriman Aydilek, Mayram Hacıoğlu, Sevgi Güngör and Yıldız Özsoy
Molecules 2026, 31(8), 1235; https://doi.org/10.3390/molecules31081235 - 8 Apr 2026
Viewed by 362
Abstract
Ocular fungal diseases are associated with severe infection and pain and, in advanced stages, can lead to vision loss. Current treatment options are limited to the topical application of conventional drugs, and the bioavailability of these drugs is quite limited due to ocular [...] Read more.
Ocular fungal diseases are associated with severe infection and pain and, in advanced stages, can lead to vision loss. Current treatment options are limited to the topical application of conventional drugs, and the bioavailability of these drugs is quite limited due to ocular barriers. In this study, a dual-drug nanodelivery system was developed to improve intraocular drug delivery by combining antifungal and anti-inflammatory therapies. Posaconazole (PSC), a broad-spectrum triazole antifungal agent, and dexketoprofen trometamol (DKP), a rapidly acting nonsteroidal anti-inflammatory drug, were co-loaded onto polymeric micelles and then incorporated into electrospun poly(vinyl alcohol)/poly(vinylpyrrolidone) (PVA/PVP) nanofiber intraocular implants. DSC, XRD, FTIR, and FESEM analyses showed that both APIs were successfully converted into nanofiber form without disrupting the micelle structure. Comparative studies with DKP solution and PSC commercial oral suspension (Noxafil® 40 mg/mL) showed that the produced micelle-loaded nanofibers provided sustained release and significantly increased ex vivo ocular permeation and penetration. In vitro antifungal activity tests demonstrated efficacy against Candida albicans, and HET-CAM toxicity tests showed that the micelle-loaded nanofibers were non-irritating and suitable for ocular application. Overall, the micelle-loaded electrospun nanofiber ocular inserts developed in this study represent a promising platform for combined antifungal and anti-inflammatory ocular therapy. Full article
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17 pages, 9674 KB  
Article
Development of Bio-Based Low-Conductivity Material from Second-Generation Biofuel Remnants
by Gabriela Guadalupe Esquivel-Barajas, Guillermo Adolfo Anaya-Ruiz, Gerardo Gallardo-Orozco, Daniela Juarez-Hernández, Yvain de los Ángeles Salinas-Delgado, Luis Alberto Bretado-Aragón, Alberto Beltrán and José Joel Román-Godínez
Energies 2026, 19(7), 1808; https://doi.org/10.3390/en19071808 - 7 Apr 2026
Viewed by 280
Abstract
The pursuit of thermal comfort in buildings is one of the main sources of energy consumption worldwide. To mitigate this expenditure, thermal insulation is required in construction. However, most conventional insulation materials come from non-renewable resources. Recently, different alternatives for generating more environmentally [...] Read more.
The pursuit of thermal comfort in buildings is one of the main sources of energy consumption worldwide. To mitigate this expenditure, thermal insulation is required in construction. However, most conventional insulation materials come from non-renewable resources. Recently, different alternatives for generating more environmentally friendly insulation from biomass have been studied. However, when using biomass, care must be taken to avoid negatively impacting the food industry. One way to address this is to use biomass waste from previous manufacturing processes. The use of waste from the production of biofuel derived from castor beans (Ricinus communis) for the manufacture of thermal insulation was successfully implemented. Castor beans were collected and used to obtain biofuel. The waste was mixed with construction materials (lime, marble dust, and cement) in different concentrations. A device for measuring thermal conductivity was built and validated. The results of scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS) are presented to characterize the material. A decrease in thermal conductivity was found in the construction material depending on the presence of micelle remnants left after oil extraction. Full article
(This article belongs to the Section B: Energy and Environment)
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38 pages, 3992 KB  
Review
Advancing Small-Molecule Immunotherapy Through Polymeric Micelle Delivery
by Kiran Suwal, Hyunji Lee, Saroj Bashyal, Donghyun Kim, Hyuk Jun Cho and Duhyeong Hwang
Pharmaceutics 2026, 18(4), 418; https://doi.org/10.3390/pharmaceutics18040418 - 29 Mar 2026
Viewed by 516
Abstract
Small-molecule immunomodulators have become important components of modern immunotherapy by targeting immune checkpoints, cytokine signaling pathways, metabolic enzymes, and intracellular kinases. Despite pharmacological rationale, many of these agents underperform clinically due to unfavorable physicochemical properties, rapid systemic clearance, limited target accumulation, and dose-limiting [...] Read more.
Small-molecule immunomodulators have become important components of modern immunotherapy by targeting immune checkpoints, cytokine signaling pathways, metabolic enzymes, and intracellular kinases. Despite pharmacological rationale, many of these agents underperform clinically due to unfavorable physicochemical properties, rapid systemic clearance, limited target accumulation, and dose-limiting toxicities, reflecting inadequate exposure control rather than a lack of target validity. Polymeric micelles, formed through the self-assembly of amphiphilic block copolymers, offer a versatile delivery platform to address these challenges by enhancing solubility, modulating pharmacokinetics, enabling stimuli-responsive release, and facilitating targeted or synchronized co-delivery. In this review, we classify representative small-molecule immunomodulators according to their immunological targets and examine the delivery constraints that shape their therapeutic performance. We then discuss design principles of polymeric micelle systems, including solubilization-driven formulations, microenvironment-responsive architectures, spatial targeting strategies, and co-delivery approaches that align cytotoxic and immunomodulatory mechanisms. Attention is given to the distinction between direct immunomodulators and cytotoxic agents that induce immunogenic cell death, highlighting how micelle-based delivery can enhance efficacy through improved exposure control. By integrating immunopharmacology with formulation science, this review outlines how polymeric micelles may advance the efficacy and safety of small-molecule immunomodulators and identifies key considerations for future translational development. Full article
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13 pages, 75560 KB  
Article
Rennet-Induced Gelation Properties of Freeze-Dried Micellar Casein Powder: Influence of Pre-Freezing Temperature
by Chuang Dong, Yun Chen, Lin Yang, Weibo Zhang, Shengbo Yu, Pengjie Wang, Zhishen Mu and Chong Chen
Gels 2026, 12(3), 265; https://doi.org/10.3390/gels12030265 - 22 Mar 2026
Viewed by 343
Abstract
Drying significantly influences the quality of micellar casein (MC) powder. This study investigated the effects of three pre-freezing temperatures (−20 °C, −80 °C, and liquid nitrogen) prior to freeze drying on the structure and rennet-induced gelation properties of MC powder. The results showed [...] Read more.
Drying significantly influences the quality of micellar casein (MC) powder. This study investigated the effects of three pre-freezing temperatures (−20 °C, −80 °C, and liquid nitrogen) prior to freeze drying on the structure and rennet-induced gelation properties of MC powder. The results showed that as the pretreatment temperature decreased, the degree of disruption to the secondary and tertiary protein structures was reduced, while the particle size gradually increased. In terms of rennet-induced gel properties, the untreated raw MC consistently outperformed all MC powder samples. Among the MC powders, the sample pre-frozen at −80 °C and then freeze-dried (FD-80) exhibited the highest gel strength and a relatively shorter rennet coagulation time. The observed microstructures of the rennet-induced gel were consistent with the rheological results, showing that samples with smaller particle sizes formed more regular and compact gel networks. In conclusion, the MC powder prepared via pre-freezing at −80 °C and then freeze-drying better preserved protein structure and demonstrated superior rennet-induced gel properties, which were closely related to particle size. This study provides theoretical insights for the application of MC powder in products such as cheese, processed cheese, and protein-fortified foods. Full article
(This article belongs to the Special Issue Rheological and Gelling Properties of Gels for Food Applications)
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41 pages, 4222 KB  
Review
Next-Generation Polysaccharide-Based Nanocarriers for Precision Medicine: Structure–Property Principles, Responsiveness, and Therapeutic Translation
by Ioannis Pispas and Aristeidis Papagiannopoulos
Macromol 2026, 6(1), 19; https://doi.org/10.3390/macromol6010019 - 18 Mar 2026
Viewed by 681
Abstract
Among the most structurally diverse biomacromolecules, polysaccharides have attracted increased attention as nanocarriers for precision medicine due to their inherent biocompatibility and versatility in functionalization. Molecular features, such as monomer composition, glycosidic linkages, charge density, and chemical modification, essentially determine the nanoscale assembly [...] Read more.
Among the most structurally diverse biomacromolecules, polysaccharides have attracted increased attention as nanocarriers for precision medicine due to their inherent biocompatibility and versatility in functionalization. Molecular features, such as monomer composition, glycosidic linkages, charge density, and chemical modification, essentially determine the nanoscale assembly process of these biopolymers, as well as their biological compatibility. This review highlights the role of these properties in the assembly process of polysaccharide-based nanocarriers leading to a variety of self-assembled nanostructures, such as polyelectrolyte complexes, protein–polysaccharide complexes, amphiphilic micelles, vesicles, hybrid systems, and nanogels, which are extensively discussed throughout the review. This review also focuses on the structure–property–function relationships of nanocarriers as applied to the rapidly developing area of precision medicine, emphasizing the problems of sustainability and reproducibility. By combining the principles of molecular engineering, supramolecular assembly, and measurable properties, this work aims to present a unified view of the molecular engineering of polysaccharide-based nanocarriers for enhanced translation potential, as well as to outline a coherent framework for the rational development of next-generation polysaccharide-based nanocarriers with improved clinical relevance. Full article
(This article belongs to the Special Issue Recent Trends in Carbohydrate-Based Therapeutics)
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30 pages, 11854 KB  
Article
Substituent Effects Control the Biological Activity of Mn(II) Imidazo[1,2-a]pyridine Complexes
by Magdalena Rydz, Tomasz Mazur, Anna Świtlicka, Urszula K. Komarnicka, Daria Wojtala, Monika K. Lesiów, Agnieszka Kyzioł, Paweł Kędzierski and Dariusz C. Bieńko
Molecules 2026, 31(6), 1007; https://doi.org/10.3390/molecules31061007 - 17 Mar 2026
Viewed by 557
Abstract
Three new Mn(II) complexes with imidazo[1,2-a]pyridine derivatives were synthesized and structurally characterized in a solid state by single crystal X-ray diffraction, FT-IR and Raman spectroscopy, and thermal analyses. The investigated compounds include [Mn(3-Climpy)2Cl2(MeOH)2] (1), [Mn(3-Brimpy) [...] Read more.
Three new Mn(II) complexes with imidazo[1,2-a]pyridine derivatives were synthesized and structurally characterized in a solid state by single crystal X-ray diffraction, FT-IR and Raman spectroscopy, and thermal analyses. The investigated compounds include [Mn(3-Climpy)2Cl2(MeOH)2] (1), [Mn(3-Brimpy)2Cl2(MeOH)2] (2), and a rare double chloro-bridged coordination polymer [Mn(impy)2Cl2]n (3). Spectroscopic studies were used to assess their potential stability in DMEM (Dulbecco’s Modified Eagle Medium), and encapsulation in Pluronic P-123 micelles improved their solubility in aqueous solution, as well as cellular uptake and selectivity. Biological evaluation revealed negligible cytotoxicity against most cancer and control cell lines, but unexpectedly high activity against pancreatic adenocarcinoma (PANC-1), exceeding that of cisplatin. Complex 2, bearing a bromine substituent in the imidazole ring, showed the strongest effects, correlating with enhanced intracellular accumulation, reactive oxygen species (ROS) generation, and mitochondrial membrane potential disruption. Molecular docking and protein binding assays demonstrated moderate affinity toward human serum albumin (HSA) and transferrin, whereas DNA interaction was weak and non-damaging. These results highlight the structure–activity relationship of Mn(II) imidazo[1,2-a]pyridine complexes and support their potential as targeted redox-active agents against pancreatic cancer, with polymeric encapsulation providing an effective strategy to enhance biological performance. Full article
(This article belongs to the Special Issue Transition Metal Complexes with Bioactive Ligands)
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17 pages, 1119 KB  
Review
Biomarkers on the Icy Jovian Moons: Can Europa Also Provide Insights into Life’s Origin?
by Julian Chela-Flores, Doron Lancet and Roy Yaniv
Life 2026, 16(3), 489; https://doi.org/10.3390/life16030489 - 17 Mar 2026
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Abstract
Within the payloads of JUICE and Europa Clipper, there are instruments suitable for the search of specific biosignatures that can diagnose life tracks in two ways. The payloads include mass spectrometers capable of measuring isotopic abundances for identifying life, and chromatography instruments testing [...] Read more.
Within the payloads of JUICE and Europa Clipper, there are instruments suitable for the search of specific biosignatures that can diagnose life tracks in two ways. The payloads include mass spectrometers capable of measuring isotopic abundances for identifying life, and chromatography instruments testing whether ocean worlds harbor amphiphile mixtures, which would lead to a lipid-first origin of life. In this paper we describe how the two missions may begin to test whether there may be large detectable excursions of stable isotopes of chemical elements on the icy surfaces of the Jovian icy moons that are substantially shifted from their expected isotopic distributions. The detection of an unambiguous signal would suggest a biogenic origin, provided care is taken to exclude abiotic thermal isotopic fractionation. Our suggested tests should be confirmed independently with other techniques. Stable isotope geochemistry on the icy Jovian moons has not yet been thoroughly discussed in the literature. In addition, we enquire whether insights into life’s origin could be retrieved from Europa’s ocean and surface, including the question of the first steps in the evolution of life. Special emphasis has been put on an approach to seek on the surface of ocean worlds chemical phenomena that are rather primitive, such as reproducing lipid micelles as roots of protocells, but nevertheless can predict a path towards life with published models. Full article
(This article belongs to the Section Origin of Life)
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