Release Of Agents Research Articles

Antibody Drug Conjugates for Cancer Therapy: From Metallodrugs to Nature-Inspired Payloads.

This review highlights significant advancements in antibody-drug conjugates (ADCs) equipped with metal-based and nature-inspired payloads, focusing on synthetic strategies for antibody conjugation. Traditional methods such us maleimide and succinimide conjugation and classical condensation reactions are prevalent for metallodrugs and natural compounds. However, emerging non-conventional strategies such as photoconjugation are gaining traction due to their milder conditions and, in an aspect which minimizes side reactions, selective formation of ADC. The review also summarizes the therapeutic and diagnostic properties of these ADCs, highlighting their enhanced selectivity and reduced side effects in cancer treatment compared to non-conjugated payloads. ADCs combine the specificity of monoclonal antibodies with the cytotoxicity of chemotherapy drugs, offering a targeted approach to the elimination of cancer cells while sparing healthy tissues. This targeted mechanism has demonstrated impressive clinical efficacy in various malignancies. Key future advancements include improved linker technology for enhanced stability and controlled release of cytotoxic agents, incorporation of novel, more potent, cytotoxic agents, and the identification of new cancer-specific antigens through genomic and proteomic technologies. ADCs are also expected to play a crucial role in combination therapies with immune checkpoint inhibitors, CAR-T cells, and small molecule inhibitors, leading to more durable and potentially curative outcomes. Ongoing research and clinical trials are expanding their capabilities, paving the way for more effective, safer, and personalized treatments, positioning ADCs as a cornerstone of modern medicine and offering new hope to patients.

Bacterial nanocellulose as a simple and tailorable platform for controlled drug release

In this study we present a proof of concept of a simple and straightforward approach for the development of a Bacterial Nanocellulose drug delivery system (BNC-DDS), envisioning the local delivery of immunomodulatory drugs to prevent foreign body reaction (FBR). Inspired by the self-adhesion behavior of BNC upon drying, we proposed a BNC laminate entrapping commercial crystalline drugs (dexamethasone-DEX and GW2580) in a sandwich system. The stability of the bilayer BNC-DDS was evidenced by the high interfacial energy of the bilayer films, 150 ± 11 and 88 ± 7 J/m2 respectively for 2 mm- and 10-mm thick films, corresponding to an increase of 7.5 and 4.4-fold comparatively to commercial tissue adhesives. In vitro release experiments unveiled the tunability of the bilayer BNC-DDS by showing extended drug release when thicker BNC membranes were used (from 16 to 47 days and from 35 to 132 days, for the bilayer-BNC entrapping DEX and GW2580, respectively). Mathematical modeling of the release data pointed to a diffusion-driven mechanism with non-fickian behavior. Overall, the results have demonstrated the potential of this simple approach for developing BNC-drug depots for localized and sustained release of therapeutic agents over adjustable timeframes.

Hot Embossing to Fabricate Parylene-Based Microstructures and Its Impact on the Material Properties.

This study aims to establish and optimize a process for the fabrication of 3D microstructures of the biocompatible polymer Parylene C using hot embossing techniques. The different process parameters such as embossing temperature, embossing force, demolding temperature and speed, and the usage of a release agent were optimized, utilizing adhesive micropillars as a use case. To enhance compatibility with conventional semiconductor fabrication techniques, hot embossing of Parylene C was adapted from conventional stainless steel substrates to silicon chip platforms. Furthermore, this adaptation included an investigation of the effects of the hot embossing process on metal layers embedded in the Parylene C, ensuring compatibility with the ultra-thin Parylene printed circuit board (PCB) demonstrated previously. To evaluate the produced microstructures, a combination of characterization methods was employed, including light microscopy (LM) and scanning electron microscopy (SEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and Fourier-transform infrared spectroscopy (FTIR). These methods provided comprehensive insights into the morphological, chemical, and structural properties of the embossed Parylene C. Considering the improved results compared to existing patterning techniques for Parylene C like plasma etching or laser ablation, the developed hot embossing approach yields a superior structural integrity, characterized by increased feature resolution and enhanced sidewall smoothness. These advancements render the method particularly suitable for diverse applications, including but not limited to, sensor optical components, adhesive interfaces for medical wearables, and microfluidic systems.

Cancer Treatment Using Nanofibers: A Review.

Currently, the number of patients with cancer is expanding consistently because of a low quality of life. For this reason, the therapies used to treat cancer have received a lot of consideration from specialists. Numerous anticancer medications have been utilized to treat patients with cancer. However, the immediate utilization of anticancer medicines leads to unpleasant side effects for patients and there are many restrictions to applying these treatments. A number of polymers like cellulose, chitosan, Polyvinyl Alcohol (PVA), Polyacrylonitrile (PAN), peptides and Poly (hydroxy alkanoate) have good properties for the treatment of cancer, but the nanofibers-based target and controlled drug delivery system produced by the co-axial electrospinning technique have extraordinary properties like favorable mechanical characteristics, an excellent release profile, a high surface area, and a high sponginess and are harmless, bio-renewable, biofriendly, highly degradable, and can be produced very conveniently on an industrial scale. Thus, nanofibers produced through coaxial electrospinning can be designed to target specific cancer cells or tissues. By modifying the composition and properties of the nanofibers, researchers can control the release kinetics of the therapeutic agent and enhance its accumulation at the tumor site while minimizing systemic toxicity. The core-shell structure of coaxial electrospun nanofibers allows for a controlled and sustained release of therapeutic agents over time. This controlled release profile can improve the efficacy of cancer treatment by maintaining therapeutic drug concentrations within the tumor microenvironment for an extended period.

Light-responsive Polymers: Developments in Drug Delivery Systems

Abstract: Photoresponsive polymers have emerged as innovative tools in the domain of drug delivery, presenting advanced solutions for controlled and targeted release of therapeutic agents. This review explores recent advances in the design and application of photoresponsive polymers, focusing on their pivotal role in light-triggered drug delivery systems. It also encompasses organic synthesis methodologies, key advancements in polymer design, and the integration of photoresponsive elements into drug carriers. Moreover, this review also focuses on the applications, challenges, and future prospects, providing a comprehensive overview of the evolving landscape of light-responsive drug delivery technologies. The information about the synthesis presented herein aims to contribute to the understanding and advancement of this dynamic field, offering insights for researchers and practitioners engaged in the development of next-generation drug delivery systems.

A benefit-risk analysis for biological control introductions based on the protection of native biodiversity.

The release of biological control agents has been an important means of controlling invasive species for over 150 years. While these releases have led to the sustainable control of over 250 invasive pest and weed species worldwide, a minority have caused environmental harm. A growing recognition of the risks of biological control led to a focus on risk assessment beginning in the 1990s along with a precipitous decline in releases. While this new focus greatly improved the safety of biological control, it came at the cost of lost opportunities to solve environmental problems associated with invasive species. A framework that incorporates benefits and risks of biological control is thus needed to understand the net environmental effects of biological control releases. We introduce such a framework, using native biodiversity as the common currency for both benefits and risks. The model is based on interactions among four categories of organisms: (1) the biological control agent, (2) the invasive species (pest or weed) targeted by the agent, (3) one or more native species that stand to benefit from the control of the target species, and (4) one or more native species that are at risk of being harmed by the released biological control agent. Conservation values of the potentially benefited and harmed native species are incorporated as well, and they are weighted according to three axes: vulnerability to extinction, the ecosystem services provided, and cultural significance. Further, we incorporate the potential for indirect risks to native species, which we consider will result mainly from the ecological process of agent enrichment that may occur if the agent exploits but does not control the target pest or weed. We illustrate the use of this framework by retrospectively analyzing the release of the vedalia beetle, Novius (= Rodolia) cardinalis, to control the cottony cushion scale, Icerya purchasi, in the Galapagos Islands. While the framework is particularly adaptable to biological control releases in natural areas, it can also be used in managed settings, where biological control protects native species through the reduction of pesticide use.

Human amniotic epithelial cells improve uterine spiral artery remodeling to ameliorate preeclampsia in a rat model†.

Preeclampsia (PE) is a multisystem pregnancy disorder characterized by impaired remodeling of placental spiral arteries, which leads to the release of pro-inflammatory cytokines and anti-angiogenic agents. However, treatment options for PE are limited, with termination of pregnancy being the only curative option. In this work, we investigated the effects of human amniotic epithelial cells (hAECs) in PE rat model. The rats were induced with lipopolysaccharide (LPS) on gestational day 14.5 followed by injection of hAECs and human umbilical cord mesenchymal stem cells 24h later. The hAECs treatment resulted in a reduction in blood pressure and proteinuria in the PE rat model. Furthermore, hAECs treatment decreased levels of pro-inflammatory cytokines, reduced inflammatory cells aggregation, and alleviated the damage to placental spiral arteries by downregulating the expression of anti-angiogenic factor and upregulating proangiogenic factor. In vitro experiments confirmed that hAECs treatment restored the proliferation, migration, and angiogenesis of LPS-damaged human umbilical vein endothelial cells. Additionally, hAECs treatment had positive effects on fetal weight and neurological development in the PE group, with no negative effects on the physical development or fertility of offspring rats. These results suggested that hAECs transplantation may be a novel adjuvant therapeutic strategy for PE by reducing the inflammatory and enhancing placental spiral artery angiogenesis.

LL-37 and bisphosphonate co-delivery 3D-scaffold with antimicrobial and antiresorptive activities for bone regeneration

This study introduces a novel 3D scaffold for bone regeneration, composed of silk fibroin, chitosan, nano-hydroxyapatite, LL-37 antimicrobial peptide, and pamidronate. The scaffold addresses a critical need in bone tissue engineering by simultaneously combating bone infections and promoting bone growth. LL-37 was incorporated for its broad-spectrum antimicrobial properties, while pamidronate was included to inhibit bone resorption. The scaffold's porous structure, essential for cell infiltration and nutrient diffusion, was achieved through a freeze-drying process. In vitro assessments using SEM and FTIR confirmed the scaffold's morphology and chemical integrity. Antimicrobial efficacy was tested against pathogens of Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa). In vivo studies in a murine model of infectious bone defect revealed the scaffold's effectiveness in reducing inflammation and bacterial load, and promoting bone regeneration. RNA sequencing of treated specimens provided insights into the molecular mechanisms underlying these observations, revealing significant gene expression changes related to bone healing and immune response modulation. The results indicate that the scaffold effectively inhibits bacterial growth and supports bone cell functions, making it a promising candidate for treating infectious bone defects. Future studies should focus on optimizing the release of therapeutic agents and evaluating the scaffold's clinical potential.

Pathophysiology and pregnancy outcomes of ascites in preeclampsia-a scoping review.

Preeclampsia is a multisystem disorder associated with defective trophoblast invasion, maternal syndrome, and capillary endothelial leak. The presence of ascites/third space fluid accumulation increases the risk of maternal morbidity and mortality. The current criteria/guidelines of preeclampsia do not establish the presence of ascites as a marker of severity or recognize the timing and need for early delivery despite associated complications. Medline and Embase databases were searched to identify relevant literature, reported up to December 2023, regarding the pathophysiology, pregnancy outcome, and management of preeclampsia complicated with ascites. A total of 5 studies on pathophysiology and eight on pregnancy outcomes met the inclusion criteria, with 41 case reports on ascites in preeclampsia. The etiopathogenesis for the development of ascites in preeclampsia includes endothelial damage, capillary hyperpermeability, release of vasoconstrictive agents, reduced intravascular oncotic pressure, and raised intraabdominal pressure. The presence of ascites represents the extreme form of microvascular damage, which also correlates with the raised sFlt-1 levels in this condition. The adverse pregnancy outcomes include increased risk of congestive heart failure, eclampsia, renal failure, disseminated intravascular coagulation, acute respiratory distress syndrome, and maternal death. The presence of ascites in preeclampsia is associated with the deterioration of the maternal condition. Hence, it is indicative of preeclampsia with severe features and requires vigilant monitoring, and prompt delivery may be considered.

A novel strategy for design of mechanically robust antifouling coatings via bifunctional domain engineering

The issue of biofouling on marine structures carries significant economic and ecological implications, necessitating the development of effective and durable antifouling coatings. Traditional organic antifouling coatings often struggle with mechanical robustness in harsh marine environments, making them fragile and highly susceptible to abrasion. To address these challenges, we propose a novel “bifunctional domain engineering” strategy for designing robust antifouling coatings that combines excellent mechanical strength of a Fe-based amorphous layer and high antifouling efficacy of an incorporated organics. The hard domains consist of Fe-based amorphous micro humps, providing a sturdy framework that enhances the coating's mechanical durability. In contrast, the soft domains comprise epoxy resin infused with Cu2O and 4,5-Dichloro-2-n-octyl-4-isothiazolin-3-one (DCOIT), offering a dual-action antifouling function via controllable antifouling agent release. Evaluation of antifouling performance by lab tests against Pseudomonas aeruginosa, Staphylococcus aureus, and Chlorella algae and practical marine field tests (for 150 days) demonstrates significant reductions in bacterial and algal adhesion (nearly 100 % resistance) with the bifunctional domain engineered coating (referred to as HSR coating), compared to pure amorphous coating. Mechanical durability tests, including abrasion and erosion experiments, underscore the HSR coating's excellent wear resistance. Importantly, the HSR coating maintains its outstanding antifouling properties even after 1000 abrasion cycles, highlighting its potential for long-term marine applications in harsh conditions. This study lays the groundwork for design of robust antifouling coatings capable of withstanding the harsh operating environments while effectively combating biofouling.

Cement pastes containing air entraining agent release the biocide octylisothiazolinone posing ecotoxicological effects

We investigated whether cement pastes are a possible source of ecotoxicologically potent substances. For this purpose, leaching according to DIN EN 16637-2 was performed on portland cement pastes as well as blast furnace slag cement with and without an air entraining agent (AEA). The AEA, consisting of wood rosin and resin, contained the stabiliser drometrizole and the biocide octylisothiazolinone (OIT), which was confirmed by our non-target screening (NTS). Our ecotoxicological studies (Daphnia magna, Aliivibrio fischeri and Desmodesmus subspicatus) of the pure cement eluates showed no effects at all. In these samples, it was possible to attribute up to 85 % of the dissolved organic carbon (DOC) to acetate, formate and diethylene glycol (DiEG). Eluates from cement pastes with AEA contained up to 70 μg/L octylisothiazolinone (OIT), and no drometrizole was found. Around 90 % of the total OIT release happened within the first 6 h. It was possible to attribute the observed ecotoxicological effects mainly to the OIT concentrations. Additional leaching with elevated sulphate concentrations (800 mg/L) did not influence the release of DOC and OIT or increase the ecotoxicological effects. As a consequence, we advise curing the cement paste for 24 h prior to use, as this largely avoids the release of OIT and the observed ecotoxicological effects.

Preparation and Evaluation of a Temperature-Sensitive Cuelure Nano-Controlled Release Agent

Preparation and Evaluation of a Temperature-Sensitive Cuelure Nano-Controlled Release Agent

Hydrogel-Based Therapies for Ischemic and Hemorrhagic Stroke: A Comprehensive Review.

Stroke remains the second leading cause of death and a major cause of disability worldwide, significantly impacting individuals, families, and healthcare systems. This neurological emergency can be triggered by ischemic events, including small vessel arteriolosclerosis, cardioembolism, and large artery atherothromboembolism, as well as hemorrhagic incidents resulting from macrovascular lesions, venous sinus thrombosis, or vascular malformations, leading to significant neuronal damage. The resultant motor impairment, cognitive dysfunction, and emotional disturbances underscore the urgent need for effective therapeutic interventions. Recent advancements in biomaterials, particularly hydrogels, offer promising new avenues for stroke management. Hydrogels, composed of three-dimensional networks of hydrophilic polymers, are notable for their ability to absorb and retain substantial amounts of water. Commonly used polymers in hydrogel formulations include natural polymers like alginate, chitosan, and collagen, as well as synthetic polymers such as polyethylene glycol (PEG), polyvinyl alcohol (PVA), and polyacrylamide. Their customizable characteristics-such as their porosity, swelling behavior, mechanical strength, and degradation rates-make hydrogels ideal for biomedical applications, including drug delivery, cell delivery, tissue engineering, and the controlled release of therapeutic agents. This review comprehensively explores hydrogel-based approaches to both ischemic and hemorrhagic stroke therapy, elucidating the mechanisms by which hydrogels provide neuroprotection. It covers their application in drug delivery systems, their role in reducing inflammation and secondary injury, and their potential to support neurogenesis and angiogenesis. It also discusses current advancements in hydrogel technology and the significant challenges in translating these innovations from research into clinical practice. Additionally, it emphasizes the limited number of clinical trials utilizing hydrogel therapies for stroke and addresses the associated limitations and constraints, underscoring the need for further research in this field.

Batch preparation and characterization of zein-based beaded nanofiber membranes for active food packaging

Active packaging can efficiently enhance the shelf life of food, realizing the encapsulation and effective release of antibacterial agents and antioxidants. Zein is a natural protein derived from corn, widely used in food packaging. In this work, zein-based nanofiber membranes (NFMs) with beaded structures for food packaging were fabricated in batch using a self-made free surface electrospinning. The characteristics of NFMs were investigated in terms of their morphologies, structures and properties. The results illustrated that the antioxidant activity of NFMs was significantly improved after adding licorice extracts. Moreover, after adding the eugenol to the zein/licorice extract NFMs, zein/licorice extract/eugenol (ZLE) NFM had outstanding antibacterial activities against Staphylococcus aureus and Escherichia coli, which effectively prolonged the shelf-life of the grapes when it was used to package grapes. It proved that ZLE NFM had great potential in food packaging applications.

Infusion of Thick-Walled Fiber Metal Laminates with Aligned Holes in the Metal Foils

The rotor blades of wind turbines are becoming increasingly longer, which increases the diameter at the blade connection. Transport problems are the result, as the rotor blades no longer fit under highway bridges, for example. The increase in diameter can be prevented by increasing the bearing strength of the laminate using fiber metal laminates (FMLs). Individual layers of fiber material are replaced by metal foils in FMLs. This work is focused on the infusion of thick-walled FMLs, with infiltration experiments being carried out in-plane and out-of-plane. For the out-of-plane infusion tests, the metal foils are perforated and it is investigated whether the holes should be arranged alternately or aligned in the metal foils. It has been shown that greater laminate thicknesses can be realized with aligned holes. For the determination of voids and dry-spots, the metal foils are treated with a release agent before infusion and after curing the laminate can be demolded ply by ply. The samples made of glass fiber-reinforced plastic (GFRP) and steel/aluminum measure 500 mm by 800 mm by 20 mm.

Utilizing Silk Sericin as a Biomaterial for Drug Encapsulation in a Hydrogel Matrix with Polycaprolactone: Formulation and Evaluation of Antibacterial Activity.

Hydrogels have emerged as a potential tool for enhancing bioavailability and regulating the controlled release of therapeutic agents. Owing to its excellent biocompatibility, silk sericin-based hydrogels have garnered interest in biomedical applications. This study focuses on synthesizing a soft hydrogel by blending silk sericin (SS) and polycaprolactone (PCL) at room temperature. The physicochemical characteristics of the hydrogels have been estimated by different analytical techniques such as UV-visible spectroscopy, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and scanning electron microscopy (SEM). The rheological studies demonstrate the non-Newtonian behavior of the hydrogels. Further, the porosity analysis indicates a commendable absorption capacity of the hydrogels. The swelling degree of the hydrogels has been checked in both distilled water and buffer solutions of different pHs (2-10). Moreover, the drug release profile of the hydrogels, using diclofenac sodium (DS) as a model drug, has revealed a substantial release of approximately 67% within the first 130 min with a drug encapsulation efficiency of 60.32%. Moreover, both the empty and the drug-loaded hydrogels have shown antibacterial properties against Gram-positive and Gram-negative bacteria, with the drug-loaded hydrogels displaying enhanced effectiveness. Additionally, the prepared hydrogels are biodegradable, demonstrating their future prospects in biomedical applications.

Multifunctional Smart Nano Biopolymers for Programmed Controlled Release of Biomolecules and Therapeutic Agents: An Overview on Modern Emerging Systems

Multifunctional Smart Nano Biopolymers for Programmed Controlled Release of Biomolecules and Therapeutic Agents: An Overview on Modern Emerging Systems

Simple and rapid identification of beef within 30 min using a new food nucleic acid release agent combined with direct-fast qPCR

Simple and rapid molecular detection technologies for authenticating animal species are urgently needed for food safety and authenticity. This study established a new direct-fast quantitative polymerase chain reaction (qPCR) detection technology for beef to achieve rapid and on-site nucleic acid detection in food. This technology can complete nucleic acid extraction in 4 min using a new type of food nucleic acid-releasing agent, followed by direct amplification of the DNA sample by fast qPCR in 25 min. The results indicated that direct-fast qPCR can specifically identify beef and can also identify 0.00001% of beef components in artificially simulated meat mixtures, with a detection precision variation coefficient of <4%. This method can be used to effectively identify beef in different food samples. As a simple, fast, and accurate molecular detection technology for beef, this method may provide a new tool for the on-site detection of beef components in food.

Injectable Nanocomposite Hydrogels Improve Intraperitoneal Co-delivery of Chemotherapeutics and Immune Checkpoint Inhibitors for Enhanced Peritoneal Metastasis Therapy.

Intraperitoneal co-delivery of chemotherapeutic drugs (CDs) and immune checkpoint inhibitors (ICIs) brings hope to improve treatment outcomes in patients with peritoneal metastasis from ovarian cancer (OC). However, current intraperitoneal drug delivery systems face issues such as rapid drug clearance from lymphatic drainage, heterogeneous drug distribution, and uncontrolled release of therapeutic agents into the peritoneal cavity. Herein, we developed an injectable nanohydrogel by combining carboxymethyl chitosan (CMCS) with bioadhesive nanoparticles (BNPs) based on polylactic acid-hyperbranched polyglycerol. This system enables the codelivery of CD and ICI into the intraperitoneal space to extend drug retention. The nanohydrogel is formed by cross-linking of aldehyde groups on BNPs with amine groups on CMCS via reversible Schiff base bonds, with CD and ICI loaded separately into BNPs and CMCS network. BNP/CMCS nanohydrogel maintained the activity of the biomolecules and released drugs in a sustained manner over a 7 day period. The adhesive property, through the formation of Schiff bases with peritoneal tissues, confers BNPs with an extended residence time in the peritoneal cavity after being released from the nanohydrogel. In a mouse model, BNP/CMCS nanohydrogel loaded with paclitaxel (PTX) and anti-PD-1 antibodies (αPD-1) significantly suppressed peritoneal metastasis of OC compared to all other tested groups. In addition, no systemic toxicity of nanohydrogel-loaded PTX and αPD-1 was observed during the treatment, which supports potential translational applications of this delivery system.

An Overview of Advanced Antimicrobial Food Packaging: Emphasizing Antimicrobial Agents and Polymer-Based Films.

The food industry is increasingly focused on maintaining the quality and safety of food products as consumers are becoming more health conscious and seeking fresh, minimally processed foods. However, deterioration and spoilage caused by foodborne pathogens continue to pose significant challenges, leading to decreased shelf life and quality. To overcome this issue, the food industry and researchers are exploring new approaches to prevent microbial growth in food, while preserving its nutritional value and safety. Active packaging, including antimicrobial packaging, has gained considerable attention among current food packaging methods owing to the wide range of materials used, application methods, and their ability to protect various food products. Both direct and indirect methods can be used to improve food safety and quality by incorporating antimicrobial compounds into the food packaging materials. This comprehensive review focuses on natural and synthetic antimicrobial substances and polymer-based films, and their mechanisms and applications in packaging systems. The properties of these materials are compared, and the persistent challenges in the field of active packaging are emphasized. Specifically, there is a need to achieve the controlled release of antimicrobial agents and develop active packaging materials that possess the necessary mechanical and barrier properties, as well as other characteristics essential for ensuring food protection and safety, particularly bio-based packaging materials.