Controlled Drug Research Articles

Development of a Controllable Intelligent Drug Delivery System for Efficient Treatment of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a complex inflammatory disease of the joints, which is often accompanied by degeneration of articular cartilage and bone erosion, seriously affecting the quality of life and psychological state of patients. RA is difficult to be cured completely, and currently the main purpose of relief is through the use of anti-inflammatory and antirheumatic drugs, hormones, and biological agents. Tofacitib is a new type of small molecule inhibitor, which has a good effect in the treatment of RA. The current direct drug delivery method has serious side effects caused by the systemic distribution of the drug, so there is a need to develop an intelligent drug delivery system to realize precise treatment. In this work, tofacitib, gallic acid, targeted molecule folic acid, and Fe(III) were selected to assemble a novel type of artificial controllable nanodrug GF-TF. The self-photoacoustic/magnetic resonance imaging (self-PA/MRI) monitored the enrichment of GF-TF in the lesion in real-time, and artificially regulated the addition of deferoxamine (DFO) at the optimal enrichment. DFO strongly chelates Fe(III) in GF-TF and causes its structure to disintegrate gradually, and the self-PA/MRI signal of GF-TF became weaker while tofacitib began to be released, thus realizing the precise and artificially controlled release of the drug under the guidance of imaging. This nanodrug not only achieves efficient aggregation of drugs in inflamed joints, but also achieves real-time monitoring and precise control of drug release through self-PA/MRI, providing a new strategy for the precise treatment of RA.

“Bamboo-like” strong and tough sodium alginate/polyacrylate hydrogel fiber with directional controlled release for wound healing promotion

Skin, as the biggest organ and outermost surface of the human body, is prone to injury due to various challenges, especially the expanding potential of accidents, which bring a huge social and economic burden. Hydrogels are emerging as the most promising candidate for wound dressings, which not only fulfill the varied requirements of dressings but also serve as drug carriers. But limited breathability, rapid drug release, and inadequate mechanical properties remains a significant challenge. Herein, we report a strong and tough sodium alginate/polyacrylate hydrogel fibers-based dressing with directional controlled drug release for wound healing promotion. Mimicking the bamboo structure, the drug solution is encapsulated within the fiber, and the rate of drug release can be modulated by controlling the wall thickness of the fiber. A cross-network structure in the hydrogel fiber through hydrogen bond and calcium ion crosslinking resulted in a 38 % increase in tensile strength. By precisely controlling the feeding process during weaving, drug-loaded fibers can be prepared at specific locations to facilitate targeted delivery to skin wound sites. Drug-loaded fabric has the breathability and biocompatibility required for dressings to promote wound healing. The findings highlight the potential of alginate/polyacrylate hydrogel fabrics for effective wound treatment.

Design, Synthesis, Antifungal Evaluation, and Three-Dimensional Quantitative Structure-Activity Relationship of Novel 5-Sulfonyl-1,3,4-thiadiazole Flavonoids.

Plant pathogenic fungi frequently disrupt the normal physiological and biochemical functions of plants, leading to diseases, compromising plant health, and ultimately reducing crop yield. This study aimed to address this challenge by identifying antifungal agents with innovative structures and novel mechanisms of action. We designed and synthesized a series of flavonoid derivatives substituted with 5-sulfonyl-1,3,4-thiadiazole and evaluated their antifungal activity against five phytopathogenic fungi. Most flavonoid derivatives demonstrated excellent antifungal activity against Botrytis cinerea (B. cinerea), Alternaria solani (A. solani), Rhizoctorzia solani (R. solani), Fusarium graminearum (F. graminearum), and Colletotrichum orbiculare (C. orbiculare). Specifically, the EC50 values of 38 target compounds against R. solani were below 4 μg/mL, among which the compounds C13 (EC50 = 0.49 μg/mL), C15 (EC50 = 0.37 μg/mL), and C19 (EC50 = 0.37 μg/mL) had the most prominent antifungal activity, superior to that of the control drug carbendazim (EC50 = 0.52 μg/mL). Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images of the cellular ultrastructures of R. solani mycelia and cells after treatment with the compound C19 revealed sprawling growth of hyphae, a distorted outline of their cell walls, and reduced mitochondrial numbers. Studying the 3D-QSAR between the molecular structure and antifungal activity of 5-sulfonyl-1,3,4-thiadiazole-substituted flavonoid derivatives could significantly improve conventional drug molecular design pathways and facilitate the development of novel antifungal leads.

Highly Efficient Synergistic Chemotherapy and Magnetic Resonance Imaging for Targeted Ovarian Cancer Therapy Using Hyaluronic Acid-Coated Coordination Polymer Nanoparticles.

The diagnosis and treatment of ovarian cancer (OC) are still a grand challenge, more than 70% of patients are diagnosed at an advanced stage with a dismal prognosis. Magnetic resonance imaging (MRI) has shown superior results to other examinations in preoperative assessment, while cisplatin-based chemotherapy is the first-line treatment for OC. However, few previous studies have brought together the two rapidly expanding fields. Here a technique is presented using cisplatin prodrug (Pt-COOH), Fe3+, and natural polyphenols (Gossypol) to construct the nanoparticles (HA@PFG NPs) that have a stable structure, controllable drug release behavior, and high drug loading capacity. The acidic pH values in tumor sites facilitate the release of Fe3+, Pt-COOH, and Gossypol from HA@PFG NPs. Pt-COOH with GSH consumption and cisplatin-basedchemotherapy plus Gossypol with pro-apoptotic effects displays asynergisticeffect forkillingtumorcells. Furthermore, the release of Fe3+ at the tumor sites promotes ferroptosis and enables MRI imaging of OC. Inthe patient-derived tumor xenograft (PDX)model, HA@PFG NPs alleviate the tumor activity. RNA sequencing analysis reveals that HA@PFG NPs ameliorate OC symptoms mainly through IL-6 signal pathways. This work combines MRI imaging with cisplatin-based chemotherapy, which holds great promise for OC diagnosis and synergistic therapy.

Injectable Salecan/hyaluronic acid-based hydrogels with antibacterial, rapid self-healing, pH-responsive and controllable drug release capability for infected wound repair

Designing materials for wound dressings with superior therapeutic benefits, self-healing and injectable characteristics is important in clinical practice. Herein, a new self-healing injectable hydrogel was prepared via thermal treatment and dynamic Schiff base reaction by mixing oxidized hyaluronic acid (OHA) and hydrazided Salecan (Sal-ADH). The versatility of the wound dressing was confirmed by studying the inherent rheological properties, high swelling rate, sustained-release behavior of the drug, pH/hyaluronidase-dependent biodegradation, in vitro antimicrobial as well as in vivo wound healing performance. The presence of the antimicrobial drug polyhexamethylene biguanide (PHMB) conferred good antimicrobial properties to the Sal-ADH/OHA/PHMB (SOP) hydrogel, which could effectively prevent wound infection (the width of the inhibition circle of SOP-0.20 hydrogel was 4.97 mm, 5.93 mm for Staphylococcus aureus and Escherichia coli, respectively). The findings suggested that SOP hydrogel exhibited remarkable self-healing and injectability properties, as well as excellent hemostasis and biocompatibility. In vivo experiments indicated that the application of SOP hydrogels would obviously accelerate wound healing and attenuate the inflammatory response while increasing collagen deposition and angiogenesis. Altogether, antibacterial SOP hydrogels with moderate mechanical properties, pH-responsive release, excellent injectability, exceptional self-healing ability and anti-inflammatory effects could expand potential applications of injectable hydrogels in the biomedical field.

Titanium Dioxide Nanomaterials: Progress in Synthesis and Application in Drug Delivery.

Background: Recent developments in nanotechnology have provided efficient and promising methods for the treatment of diseases to achieve better therapeutic results and lower side effects. Titanium dioxide (TiO2) nanomaterials are emerging inorganic nanomaterials with excellent properties such as low toxicity and easy functionalization. TiO2 with special nanostructures can be used as delivery vehicles for drugs, genes and antigens for various therapeutic options. The exploration of TiO2-based drug delivery systems shows great promise for translating nanotechnology into clinical applications; Methods: Comprehensive data on titanium dioxide were collected from reputable online databases including PubMed, GreenMedical, Web of Science, Google Scholar, China National Knowledge Infrastructure Database, and National Intellectual Property Administration; Results: In this review, we discuss the synthesis pathways and functionalization strategies of TiO2. Recent advances of TiO2 as a drug delivery system, including sustained and controlled drug release delivery systems were introduced. Rigorous long-term systematic toxicity assessment is an extremely critical step in application to the clinic, and toxicity is still a problem that needs to be closely monitored; Conclusions: Despite the great progress made in TiO2-based smart systems, there is still a great potential for development. Future research may focus on developing dual-reaction delivery systems and single-reaction delivery systems like redox and enzyme reactions. Undertaking thorough in vivo investigations is necessary prior to initiating human clinical trials. The high versatility of these smart drug delivery systems will drive the development of novel nanomedicines for personalized treatment and diagnosis of many diseases with poor prognosis.

Injectable and 3D Extrusion Printable Hydrophilic Silicone-Based Hydrogels for Controlled Ocular Delivery of Ophthalmic Drugs.

While silicone elastomers have found widespread use in the biomedical industry, 3D printing them has proven to be difficult due to the material's slow drying time, low viscosity, and hydrophobicity. Herein, we arrested the hydrophilic silicone (HS) macrochains into a semi-interpenetrating polymer network (semi-IPN) via an in situ photogelation-assisted 3D microextrusion printing technique. The flow behavior of the pregel solutions and the mechanical properties of the printed HS hydrogels were tested, showing a high elastic modulus (approximately 15 kPa), a low tan δ, high elasticity, and delayed network rupturing. The uniaxial compression tests demonstrated a nearly negligible permanent deformation, suggesting that the printed hybrid hydrogel maintained its elastic properties. Drug loading and diffusion in the microporous hydrogel are shown via the non-Fickian anomalous transport mechanism, leading to highly tunable loading/releasing profiles (approximately 20% cumulative release) depending on the HS concentration. The drug encapsulation exhibits exceptional stability, remaining intact without any degradation even after a storage period of 1 month. As far as we know, this is the first soft biomaterial based on HS that functions as an exceptional controlled drug delivery device.

Leveraging the Physicochemical Attributes of Biomimetic Hydrogel Nanocomposites in Stem Cell Differentiation.

The field of tissue engineering has witnessed significant advancements with the advent of hydrogel nanocomposites (HNC), emerging as a highly promising platform for regenerative medicine. HNCs provide a versatile platform that significantly enhances the differentiation of stem cells into specific cell lineages, making them highly suitable for tissue engineering applications. By incorporating nanoparticles, the mechanical properties of hydrogels, such as elasticity, porosity, and stiffness, are improved, addressing common challenges such as short-term stability, cytotoxicity, and scalability. These nanocomposites also exhibit enhanced biocompatibility and bioavailability, which are crucial to their effectiveness in clinical applications. Furthermore, HNCs are responsive to various triggers, allowing for precise control over their chemical properties, which is beneficial in creating 3D microenvironments, promoting wound healing, and enabling controlled drug delivery systems. This review provides a comprehensive overview of the production methods of HNCs and the factors influencing their physicochemical and biological properties, particularly in relation to stem cell differentiation and tissue repair. Additionally, it discusses the challenges in developing HNCs and highlights their potential to transform the field of regenerative medicine through improved mechanotransduction and controlled release systems.

Turning waste into wonder: Recycling agricultural wastes for controlled drug delivery systems

To make these materials, we used a simple oven muffle furnace for heating the sugarcane bagasse agricultural wastes (SCB) under controlled conditions transformed it into valuable carbon nanostructures. We discovered that both graphene oxide (GO) and carbon nanotubes (CNTs) was acted like carriers for drugs for controllable drug release. This makes them ideal for creating drug delivery systems. Instead of swallowing a pill that releases its entire dose at once, these carbon carriers can slowly release the medication over time, providing a more sustained and controlled effect. The study showed that CNTs were particularly good at holding onto drugs compared to GO. This makes them promising candidates for future drug delivery applications.

Bioactivity-Guided Isolation of Antistroke Compounds from Gymnadenia conopsea (L.) R. Br.

A bioactivity-guided separation strategy was used to identify novel antistroke compounds from Gymnadenia conopsea (L.) R. Br., a medicinal plant. As a result, 4 undescribed compounds (1-2, 13, and 17) and 13 known compounds, including 1 new natural product (3), were isolated from G. conopsea. The structures of these compounds were elucidated through comprehensive spectroscopic techniques, such as 1D/2D nuclear magnetic resonance (NMR) spectroscopy, high-resolution electrospray ionization mass spectrometry (HRESIMS), and quantum chemical calculations. An oxygen-glucose deprivation/reoxygenation (OGD/R)-injured rat pheochromocytoma (PC12) cell model was used to evaluate the antistroke effects of the isolates. Compounds 1-2, 10-11, 13-15, and 17 provided varying degrees of protection against OGD/R injury in the PC12 cells at concentrations of 12.5, 25, and 50 µM. Among the tested compounds, compound 17 demonstrated the most potent neuroprotective effect, which was equivalent to that of the positive control drug (edaravone). Then, transcriptomic and bioinformatics analyses were conducted to reveal the regulatory effect of compound 17 on gene expression. In addition, quantitative real-time PCR (qPCR) was performed to verify the results of the transcriptomic and bioinformatics analyses. These results suggest that the in vitro antistroke effect of compound 17 may be associated with the regulation of the Col27a1 gene. Thus, compound 17 is a promising candidate for the development of novel antistroke drugs derived from natural products, and this topic should be further studied.

100 Impact of luteal blood perfusion and estrus expression on pregnancy rates of beef cows exposed to embryo transfer

Abstract This study aimed to evaluate the impact of luteal blood perfusion and estrus expression on pregnancy rates of beef cows exposed to fixed-timed embryo transfer (FTET). Postpartum beef cows (n = 763) from 22 locations were exposed to a 7-d Select Synch + controlled internal drug releasing (CIDR) and breeding indicator patches were affixed upon CIDR removal. Estrus expression was assessed twice daily for 72 h and a 100-µg injection of gonadotropin-releasing hormone was administered to cows that failed to express estrus 72 h after CIDR removal. Brightness mode ultrasonography of the corpus luteum (CL) was conducted to select recipients for FTET 9 d after CIDR removal. Suitable recipients were assigned to receive a single fresh or frozen embryo derived from either in vitro (IVF) or in vivo (IVD) method. After embryo recipient selection, CL morphometries and blood perfusion (BP) were then assessed at the time of embryo transfer via transrectal ultrasonography. Embryo recipients were categorized according to CL area [small (< 3 cm²), medium (3 to 4 cm²), or large (> 4 cm²)] and based on the percentage of luteal area with blood perfusion signals [low (< 25%), medium (25 to 45%), or high (> 45%)]. Pregnancy diagnoses were performed between d 60 and 90 of gestation. Cows that failed to express estrus prior FTET had decreased (P ≤ 0.02) luteal area, luteal diameter, and pregnancy rates compared with cows that expressed estrus. Luteal area category had no effect (P = 0.61) on pregnancy rates. Embryo recipients that expressed estrus had similar (P = 0.12) luteal blood perfusion compared with recipients that failed to express estrus. Embryo recipients with high (P = 0.02) and medium (P = 0.05) BP had greater pregnancy rates compared with embryo recipients with low BP. There was no interaction between estrus expression and luteal BP (P = 0.84). In summary, estrus expression and luteal BP positively impacted pregnancy rates to embryo transfer and may be used to facilitate embryo recipient selection.

Peptide-Amphiphilic Nanoassemblies as a Responsive Senolytic Navigator for Targeted Removal of Senescent Cardiomyocytes to Ameliorate Heart Failure.

Heart failure (HF) represents the terminal stage of numerous cardiovascular disorders and lacks effective therapeutic strategies. The accumulation of senescent cardiomyocytes is a cardinal characteristic of HF, contributing to myocardial dysfunction and deteriorating the myocardial microenvironment through the development of senescence-associated secretory phenotypes (SASPs), ultimately culminating in pathological remodeling. Senolytics, a promising therapeutic strategy that selectively induces apoptosis in senescent cells, faces challenges due to nonspecific effects, raising concerns for clinical implementation. In this study, we developed peptide-amphiphilic nanoassemblies as responsive drug navigators for targeted delivery. The modular nanoassemblies comprise a hydrophilic domain containing a CD9-binding peptide, a hydrophobic domain incorporating a reactive oxygen species (ROS)-responsive motif, and an alkyl tail for encapsulation of the senolytic ABT263. The CD9-targeted and ROS-responsive nanoassemblies (AP@ABT263) specifically recognized senescent cardiomyocytes and modulated the release of ABT263 in the presence of elevated intracellular ROS levels. AP@ABT263 treatment significantly enhanced the targeted delivery of ABT263 to senescent cells in both in vitro and in vivo while showing minimal toxicity to normal cardiomyocytes and other tissues. Our findings provide compelling evidence that AP@ABT263 efficiently eradicated senescent cardiomyocytes, enhanced cardiac function, and attenuated the deleterious effects of SASP, thereby preventing adverse cardiac remodeling. In summary, AP@ABT263 represents a highly promising approach for responsive and controlled drug release in senescent cardiomyocytes, providing valuable insights into the development of intelligent pharmaceutical interventions for the management of HF.

Effect of remimazolam on intra-operative hypotension: Systematic review and meta-analysis of randomised controlled trials.

Hypotension is common during anaesthesia. Increasing number of studies have reported that remimazolam may be associated with lower incidence of intra-operative hypotension compared with other anaesthetics. However, the results remain controversial. This study aimed to evaluate the influence of remimazolam on intra-operative hypotension and its related outcomes (hypoxaemia, bradycardia and time to awake). A systematic review of randomised controlled trials (RCTs) with meta-analyses. PubMed, Cocharane and Embase databases were searched to identify eligible RCTs published up to June 2024. RCTs published in English were eligible for inclusion. The study patients were 18 years or older who were administered with remimazolam and other positive control agents in either the pre-operative or intra-operative period. The incidence of intra-operative hypotension was identified in these studies. This study evaluated 34 trials including 4847 individuals. Basing on moderate-certainty evidence, we found that remimazolam administration reduced the incidence of intra-operative hypotension [risk ratio (RR) = 0.48, 95% confidence interval (95% CI): 0.41 to 0.57] and bradycardia (16 studies, n = 2869, RR = 0.40, 95% CI: 0.29 to 0.54). No difference was observed in the incidence of hypoxaemia (RR = 0.70, 95% CI: 0.48 to 1.01) and time to awake (MD = -0.91, 95% CI: -2.42 to 0.60). The remarkable association between remimazolam and hypotension remained robust and significant, regardless of general anaesthesia or procedural sedation (P < 0.01, I2 = 82%). No significant difference was found between different control drugs (P = 0.97, I2 = 82%). Moderate-quality evidence shows that remimazolam administration to patients undergoing general anaesthesia or procedural sedation decreases the incidence of intra-operative hypotension and bradycardia.

Interactions of human serum albumin with phosphate and Tris buffers: impact on paclitaxel binding and nanoparticles self-assembly

Aim To investigate the conformational changes in human serum albumin (HSA) caused by chemical (CD) and thermal denaturation (TD) at pH 7.4 and 9.9, crucial for designing controlled drug delivery systems with paclitaxel (PTX). Methods Experimental and computational methods, including differential scanning calorimetry (DSC), UV-Vis and intrinsic fluorescence spectroscopy, mean diameter, polydispersity index (PDI), ζ-potential, encapsulation efficiency (EE), in vitro release and protein docking studies were conducted to study the HSA denaturation and nanoparticles (NPs) preparation. Results TD at pH 7.4 produced smaller NPs (287.1 ± 12.9 nm) than CD at pH 7.4 with NPs (584.2 ± 47.7 nm). TD at pH 9.9 exhibited high EE (97.3 ± 0.2%w/w) with rapid PTX release (50% within 1h), whereas at pH 7.4 (96.4 ± 2.1%w/w), release only 40%. ζ-potentials were around −30 mV. Conclusion Buffer type and pH significantly influence NP properties. TD in PBS at pH 7.4, provided optimal conditions for a stable and efficient drug delivery system.

Exploring Holy Basil's Bioactive Compounds for T2DM Treatment: Docking and Molecular Dynamics Simulations with Human Omentin-1.

Type 2 Diabetes Mellitus (T2DM) presents a substantial health concern on a global scale, driving the search for innovative therapeutic strategies. Phytochemicals from medicinal plants, particularly Ocimum tenuiflorum (Holy Basil), have garnered attention for their potential in T2DM management. The increased focus on plant-based treatments stems from their perceived safety profile, lower risk of adverse effects, and the diverse range of bioactive molecules they offer, which can target multiple pathways involved in T2DM. Computational techniques explored the binding interactions between O. tenuiflorum phytochemicals and Human Omentin-1, a potential T2DM target. ADMET evaluation and targeted docking identified lead compounds: Luteolin (-4.84 kcal/mol), Madecassic acid (-4.12 kcal/mol), Ursolic acid (-5.91 kcal/mol), Stenocereol (-5.59 kcal/mol), and Apigenin (-4.64 kcal/mol), to have a better binding affinity to target protein compared to the control drug, Metformin (-2.01 kcal/mol). Subsequent molecular dynamics simulations evaluated the stability of Stenocereol, Luteolin, and Metformin complexes for 200 nanoseconds, analysing RMSD, RMSF, RG, SASA, PCA, FEL, and MM-PBSA parameters. Results indicated Stenocereol's strong binding affinity with Omentin-1, suggesting its potential as a potent therapeutic agent for T2DM management. These findings lay the groundwork for further experimental validation and drug discovery endeavours.

A comparative study of sensitizers and liposome composition in radiation-induced controlled drug release for cancer therapy

This study investigates drug-loaded liposomes designed for controlled release under ionizing radiation to refine cancer treatment precision. Liposomes as carriers enable targeted chemotherapy delivery, reducing healthy tissue damage risk. Liposomes containing poly- or mono-unsaturated fatty acids and various sensitizing agents were assessed for responsiveness to UV light and γ photon irradiation including rose bengal (RB), protoporphyrin IX (PPIX), verteporfin (VP), cercosporin (CERC) and hypericin (HYP). Carboxyfluorescein (CF) was used as a surrogate for drug release measurements. VP and PPIX induced rapid drug release and lipid peroxidation under UV light, while RB prompted quick drug release under UV light and a modest immediate release under γ irradiation, eventually reaching full release a few hours after irradiation, demonstrating dose-dependent effects. Smaller liposomes displayed accelerated release, emphasizing size-dependent kinetics. In vitro analyses evaluated radiosensitizing effects of RB-loaded liposomes. Clonogenic assays indicated that RB-filled liposomes had minimal direct radiobiological effects but increased indirect radiation damage, as shown by the curvature of the cell survival curve. Our study sheds light on factors influencing liposomal drug release under ionizing radiation, spotlighting RB as a promising radiosensitizer requiring further investigation for cancer therapy potential.

Toward the Integration of Machine Learning and Molecular Modeling for Designing Drug Delivery Nanocarriers.

The pioneering work on liposomes in the 1960s and subsequent research in controlled drug release systems significantly advances the development of nanocarriers (NCs) for drug delivery. This field is evolved to include a diverse array of nanocarriers such as liposomes, polymeric nanoparticles, dendrimers, and more, each tailored to specific therapeutic applications. Despite significant achievements, the clinical translation of nanocarriers is limited, primarily due to the low efficiency of drug delivery and an incomplete understanding of nanocarrier interactions with biological systems. Addressing these challenges requires interdisciplinary collaboration and a deep understanding of the nano-bio interface. To enhance nanocarrier design, scientists employ both physics-based and data-driven models. Physics-based models provide detailed insights into chemical reactions and interactions at atomic and molecular scales, while data-driven models leverage machine learning to analyze large datasets and uncover hidden mechanisms. The integration of these models presents challenges such as harmonizing different modeling approaches and ensuring model validation and generalization across biological systems. However, this integration is crucial for developing effective and targeted nanocarrier systems. By integrating these approaches with enhanced data infrastructure, explainable AI, computational advances, and machine learning potentials, researchers can develop innovative nanomedicine solutions, ultimately improving therapeutic outcomes.

In-Vitro and In-Silico Studies of Brevifoliol Ester Analogues against Insulin Resistance Condition.

Brevifoliol is a diterpenoid that occurs naturally in the plants of Taxus genus and is widely used as chemotherapy agent for the management of cancer. A series of semisynthetic esters analogues of brevifoliol were prepared by Steglich esterification and attempted for their pharmacological potential against insulin resistance conditions using in-vitro and in-silico assays. The aim of this study is to understand the pharmacological potential of eighteen semisynthetic analogs through Steglich esterification of Brevifoliol against insulin resistance condition Methods: In the in-vitro study, insulin resistance condition was induced in skeletal muscle cells using TNF-α, pro-inflammatory cytokine and these cells were treated with brevifoliol analogues. The most potent analouge was further validated using in-silico docking study against the tumor necrosis factor (TNF-α) (PDB ID: 2AZ5) and Human Insulin Receptor (PDB ID: 1IR3), using the Auto dock Vina v0.8 program. Although, all the analogues of Brevifoliol significantly exhibited the pharmacological potential. Among all, analogue 17 was most potent in reversing the TNF-α induced insulin resistance condition in skeletal muscle cells and also to inhibit the production of TNF-α in LPSinduced inflammation in macrophage cells in a dose-dependent manner. Similarly, in-silico molecular docking studies revealed that analogue 17 possesses a more promising binding affinity than the selected control drug metformin toward the TNF-α and insulin receptor. These findings suggested the suitability of analogue 17 as a drug-like candidate for further investigation toward the management of insulin resistance conditions.

Controllable Contact-Destructive Hydrogel Actuators.

Constructing hydrogels with spatially heterogeneous structures are crucial for unlocking novel applications. To this end, selectively removing a specific portion of hydrogels by facile and intricate destructive strategies is worth exploring. Herein, a "contact-destructive" hydrogel actuator is presented, composed of a dynamic hydrogel network doped with hydrophilic polyethylene glycol (PEG). The destructive behavior of the hydrogel actuator is attributed to the surface tension-induced spreading effect and the enhanced water absorption due to the additive PEG. Parameters that act on these mechanisms are used to control the destruction of the hydrogel. During the destructive process, the hydrogel actuator exhibits locomotion routes predetermined by the graphic pattern with the aid of 3D printing. Additionally, such self-destructive behavior can be terminated by UV light irradiation when PEG is replaced with poly(ethylene glycol) diacrylate (PEGDA). Significantly, diverse applications including controllable 3D structures collapse, self-erasing, and on-demand cell release, are realized with such self-destructive hydrogel. These results demonstrate that the present hydrogel has great values in soft robotics, anti-counterfeiting, controlled drug delivery, and other related fields.

Nanofiber-Based Drug Delivery Systems: A Review on Its Applications, Challenges, and Envisioning Future Perspectives.

Nanomaterials, especially nanofibers, hold considerable promise as drug delivery systems (DDS) by providing targeted administration of drugs due to their unique properties, such as large surface area, high porosity, and mechanical robustness. Nanofibers can be fabricated using various techniques like electrospinning, self-assembly, phase separation, and template synthesis, offering properties such as adjustable size, shape, high precision, and biodegradability. Additionally, features such as multiple target functionalization, controlled release of the drug, and prolonged circulation of the drug make nanofibers particularly suitable for biomedical applications, including drug delivery, tissue regeneration, and biosensing. This comprehensive review explores the characteristics, types, fabrication methods, and applications of nanofibers. Diverse types of polymer nanofibers are used in drug delivery, such as blended nanofibers, core-shell nanofibers, and layer-by-layer assembly, each demonstrating their own advantages in controlled drug release and targeted therapy. Electrospun nanofibers are extensively utilized in biomedical applications due to their superior mechanical performance and high porosity and advancements in coaxial electrospinning enabling the fabrication of core-shell nanofibers, offering controlled drug release kinetics and protection of loaded molecules. These nanofibers demonstrate enhanced bioactivity and biocompatibility and can find application in tissue engineering. Furthermore, this review addresses the challenges associated with nanofiber production, including reproducibility and scalability. Nanofibers exhibit the potential to revolutionize medical treatment across diverse therapeutic areas. Future research directions and challenges in nanofiber-based drug delivery discussed in this review offer guidance for further advancements in this rapidly evolving field.