Release Of Agents Research Articles

Esterase responsive release of anti-cancer agents from conjugated lipid nanocarrier and the regulatory considerations.

The release of active agents in tumors rather than normal tissues, limits systemic exposure and toxicities. Targeting over-expressed esterase enzymein the tumor microenvironment can selectively release immune-active agents like Programmed Death-1 (PD-1) and PD-1 ligand inhibitors fromester-sensitivelipidnanocarriers, offering a novel approach compared with conventional therapies. PD-1 and PD-L1 association cause T-cell inactivation, whereas blocking their association improves their cytotoxic mechanism. The patent application US2022/0080051-A1 discloses a novel immune-active agent conjugated with lipid to form a nanocarrier for esterase-sensitive release. These nanocarriers selectively enter leaky vasculature of tumors through enhanced permeability and retention effect, undergo ester cleavage to release agents, and are reported to increase bioavailabilityby 24 times. Further, with other agents or alone it achieves targeted synergistic cancer therapy. Also, the current patent spotlight delves into the crucial formulation considerations necessary for obtaining successful approval of lipidic nano products from relevant regulatory authorities.

Electrospun drug-loaded scaffolds for nervous system repair.

Nervous system injuries, encompassing peripheral nerve injury (PNI), spinal cord injury (SCI), and traumatic brain injury (TBI), present significant challenges to patients' wellbeing. Traditional treatment approaches have limitations in addressing the complexity of neural tissue regeneration and require innovative solutions. Among emerging strategies, implantable materials, particularly electrospun drug-loaded scaffolds, have gained attention for their potential to simultaneously provide structural support and controlled release of therapeutic agents. This review provides a thorough exploration of recent developments in the design and application of electrospun drug-loaded scaffolds for nervous system repair. The electrospinning process offers precise control over scaffold characteristics, including mechanical properties, biocompatibility, and topography, crucial for creating a conducive environment for neural tissue regeneration. The large surface area of the resulting fibrous networks enhances biomolecule attachment, influencing cellular behaviors such as adhesion, proliferation, and migration. Polymeric electrospun materials demonstrate versatility in accommodating a spectrum of therapeutics, from small molecules to proteins. This enables tailored interventions to accelerate neuroregeneration and mitigate inflammation at the injury site. A critical aspect of this review is the examination of the interplay between structural properties and pharmacological effects, emphasizing the importance of optimizing both aspects for enhanced therapeutic outcomes. Drawing upon the latest advancements in the field, we discuss the promising outcomes of preclinical studies using electrospun drug-loaded scaffolds for nervous system repair, as well as future perspectives and considerations for their design and implementation. This article is categorized under: Implantable Materials and Surgical Technologies > Nanomaterials and Implants Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement Therapeutic Approaches and Drug Discovery > Emerging Technologies.

Delamination Avoidance in Epoxy Wet-Wound REBCO Coils by Release Agent Coating

Delamination Avoidance in Epoxy Wet-Wound REBCO Coils by Release Agent Coating

Studies on Encapsulation of Gas Releasing Agent in Ca-Alginate Beads and Controlled Release Pattern of the Beads

Calcium alginate beads have been used to control release gases and volatile compounds for agricultural applications, drug delivery, waste treatment, and food product enhancement. The release rate of the gas and vapor depends on the diffusion of gas and vapor through the Ca-alginate gel matrix. However, the knowledge about the effect of process variables on the diffusion rate of gas and vapor still needs to be improved. Therefore, this study aims to investigate the effect of alginate concentration, gas release agent concentration, and bead size on the concentration of gas released from Ca-alginate beads. In this study, calcium carbonate was used as the model gas release agent, encapsulated in Ca-alginate beads to release carbon dioxide when the beads reacted with an acetic acid solution. The results showed that the concentration of carbon dioxide released by the beads depended on the bead diameter. The gas release rate was increased when the diameter of the beads was increased. The total amount of gas produced by the large beads was observed to be higher than that of small beads. Compared to small beads, large beads take longer to react completely to produce carbon dioxide gas. It was also found that the amount of carbon dioxide produced by the Ca-alginate beads was inversely proportional to alginate concentration but directly proportional to calcium carbonate concentration. The results indicated that the gas diffusion rate of the Ca-alginate beads can be tailored by adjusting the process variables of the Ca-alginate bead encapsulation process.

Endogenous Calcium-Supported dynamic Copper(II)-Crosslinked Gel depot for in situ disulfiram activation and synergistic cancer therapy

The development of smart therapeutic scaffolds to improve chemotherapeutic efficacy and enhance antitumor immunity remains a considerable challenge. In this study, we engineered a therapeutic copper ion-crosslinked gel depot based on alginate to enhance disulfiram (DSF)-mediated cancer chemoimmunotherapy. This gel depot maintained structural stability through ion coordination exchange with the calcium ions in body fluids and continuously created an antitumor diethyldithiocarbamate-copper complex (CuET), which led to the sustained release of various therapeutic agents in vivo. The generated CuET not only had a direct antitumor effect due to its cytotoxicity but also effectively induced the immunogenic death of cancer cells. These factors coregulated the immunosuppressed tumor microenvironment with the released DSF, thus sensitizing the systemic immune response and improving the efficacy of anti-programmed cell death-ligand 1 antibody (aPD-L1)-mediated immune checkpoint blockade. The results indicated that this endogenous calcium-supported therapeutic copper(II)-crosslinked gel depot could effectively improve the tumor immune microenvironment, leading to enhanced synergistic antitumor efficacy in vivo.

Microneedle-mediated nanomedicine to enhance therapeutic and diagnostic efficacy.

Nanomedicine has been extensively explored for therapeutic and diagnostic applications in recent years, owing to its numerous advantages such as controlled release, targeted delivery, and efficient protection of encapsulated agents. Integration of microneedle technologies with nanomedicine has the potential to address current limitations in nanomedicine for drug delivery including relatively low therapeutic efficacy and poor patient compliance and enable theragnostic uses. In this Review, we first summarize representative types of nanomedicine and describe their broad applications. We then outline the current challenges faced by nanomedicine, with a focus on issues related to physical barriers, biological barriers, and patient compliance. Next, we provide an overview of microneedle systems, including their definition, manufacturing strategies, drug release mechanisms, and current advantages and challenges. We also discuss the use of microneedle-mediated nanomedicine systems for therapeutic and diagnostic applications. Finally, we provide a perspective on the current status and future prospects for microneedle-mediated nanomedicine for biomedical applications.

Strawberry guava invasion of a Hawaiian rainforest: Changing population patterns

AbstractStrawberry guava (waiawī, Psidium cattleyanum Sabine, Myrtaceae) is a small tree invasive on oceanic islands where it may alter forest ecosystem processes and community structure. To better understand the dynamics of its invasion in Hawaiian rainforests in anticipation of the release of a biocontrol agent, we measured growth and abundance of vertical stems ≥0.5 cm DBH for 16 years (2005–2020) in Metrosideros‐Cibotium rainforest on windward Hawai'i Island. Specifically, we compared the growth and abundance of both shoots (originating from seed or from the root mat) and sprouts (originating above ground from established stems) in four replicate study sites. Mean stem density increased from 9562 stems/ha in 2005 to 26,595 stems/ha in 2020, the majority of which were stems <2 cm DBH. Early in the invasion, both density and per capita recruitment of shoots was greater than that of sprouts, but as overall stem density increased, sprout abundance and recruitment came to surpass that of shoots. Relative growth rates among small stems <2 cm DBH declined over time for both shoots and sprouts, but relative growth rates of sprouts were consistently greater than that of shoots after the first 3 years. The capacity of strawberry guava to recruit from both shoots and sprouts facilitates its invasion of rainforest, its persistence in the forest understory, and its response to canopy opening. Strawberry guava thus poses a considerable risk of stand replacement for Hawaiian rainforests. Stand management will require perpetual efforts to control both seed production and sprouting.

Tabletized Nanomedicine: From the Current Scenario to Developing Future Medicine.

The limitations of conventional therapeutic treatments prevailed in the development of nanotechnology-based medical formulations, termed nanomedicine. Nanomedicine is an advanced medicine that often consists of therapeutic agent(s) embedded in biodegradable or biocompatible nanomaterial-based formulations. Among nanomedicine approaches, tablet (oral) nanomedicine is still under development. In tabletized nanomedicine, the dynamic interplay between nanoformulations and the intricate milieu of the gastrointestinal tract simulates a pivotal role, particularly accentuating the influence exerted upon the luminal, mucosal, and epithelial cells. In this work, we document the perspectives and opportunities of nanoformulations toward the development of tabletized nanomedicine. This review also unveils the notion of integrating nanomedicine within a tablet formulation, which facilitates the controlled release of drugs, biomolecules, and agent(s) from the formulation to achieve a better therapeutic response. Finally, an attempt was made to explore current trends in nanomedicine technology such as bacteriophage, probiotic, and oligonucleotide tabletized nanomedicine and the combination of nanomedicine with imaging agents, i.e., nanotheranostics.

Responsive Supramolecular Polymers for Diagnosis and Treatment.

Stimuli-responsive supramolecular polymers are ordered nanosized materials that are held together by non-covalent interactions (hydrogen-bonding, metal-ligand coordination, π-stacking and, host-guest interactions) and can reversibly undergo self-assembly. Their non-covalent nature endows supramolecular polymers with the ability to respond to external stimuli (temperature, light, ultrasound, electric/magnetic field) or environmental changes (temperature, pH, redox potential, enzyme activity), making them attractive candidates for a variety of biomedical applications. To date, supramolecular research has largely evolved in the development of smart water-soluble self-assemblies with the aim of mimicking the biological function of natural supramolecular systems. Indeed, there is a wide variety of synthetic biomaterials formulated with responsiveness to control and trigger, or not to trigger, aqueous self-assembly. The design of responsive supramolecular polymers ranges from the use of hydrophobic cores (i.e., benzene-1,3,5-tricarboxamide) to the introduction of macrocyclic hosts (i.e., cyclodextrins). In this review, we summarize the most relevant advances achieved in the design of stimuli-responsive supramolecular systems used to control transport and release of both diagnosis agents and therapeutic drugs in order to prevent, diagnose, and treat human diseases.

Challenges of Bioterrorism: An Indian Perspective

Bioterrorism is the deliberate release of viruses, bacteria, toxins, or other harmful agents to cause illness or death in people, animals, or plants. A biological weapon is useful to terrorists mainly as a method of creating mass panic and disruption to a state or a country. Bioterrorism agents are classified as categories A, B, and C. Bioterrorism imposes particularly heavy demands on the nation’s public health and health care system because ultimately it will be the public health system that will be called on to mitigate and ameliorate the consequences of a bioterrorism attack. India is the second-most populous country in the world and has a diverse demography consisting of various religions, cultures, and languages. The unique nature of India’s population makes it vulnerable to bioterrorism attacks that can result in catastrophic consequences. This review article aims to focus on the challenges of bioterrorism from Indian perspective and to outline the methods on preparedness and prevention of bioterror attacks.

Variable Shape Tooling for Composite Manufacturing: A Systematic Review

The choice of material, manufacturing process, and molding tool significantly affects the quality, environmental impact, and cost efficiency of composite components. Producing one-piece hollow profiles with smooth inner surfaces and undercuts presents major challenges for conventional mold concepts. There is yet no thorough review of shape-variable mandrels in composite manufacturing to be found in the literature. This paper provides an overview of research on shape memory polymers and other shape-variable materials used in tooling applications for composite manufacturing. This work covers shape memory, heat shrink, and other deformable tooling concepts that enable the production of one-piece Type V pressure vessels, air intake ducts, or curved struts and tubes. A systematic literature review in combination with a state-of-the-art open-source active learning tool ASReview is conducted. Fifteen relevant studies were identified. Research on shape-variable tooling is mainly conducted by three research groups in the USA and the PRC. The tooling is mostly made of unreinforced thermosets, especially styrene-based ones. Thermoplastic resins are less common, and reinforcements limit the usable elongation in the temporary shape. The shape variability is either a shape memory and/or a softening process, which, in all studies, is activated by heating. Release agents are widely used to ease demolding. No ecological or economical assessment of the manufacturing methods was conducted in the reviewed studies. Three fields for further research that could be identified are as follows: (1) thorough ecological end economical assessment of shape-variable mandrels in comparison with conventional tooling; (2) thermoplastic shape memory polymer mandrels; and (3) further investigation of simulation capabilities for shape memory mandrels.

CDI crosslinked chitosan/poly (vinyl alcohol) electrospun nanofibers loaded with Achillea millefolium and Viola extract: A promising wound dressing

Biopolymer-based electrospun mats, mimicking the extracellular matrix, have been extensively explored in biomedical applications. This study compares Achillea millefolium (AM) and Viola (V) extracts for developing a biocompatible wound dressing. The extracts were incorporated into a Chitosan/polyvinyl alcohol (CS/PVA) matrix via electrospinning. Crosslinking with Carbonyldiimidazole (CDI) improved chemical stability, water resistance, and biodegradability. The resulting mats exhibited flawless interconnected nanofibers, confirming the presence of AM and Viola extracts as analyzed via FTIR. Significant differences were observed between these two herbal extracts, particularly in mechanical properties, with tensile strengths of 6.9 MPa for AM and 17.2 MPa for Viola. Viola extract demonstrated robust antibacterial properties, producing an 8.2 mm inhibition zone against Staphylococcus aureus, compared to AM's 30 %. The release of therapeutic agents indicated an initial rapid phase, followed by a controlled 72 h release at a consistent rate. Notably, Viola extract led to 80.9 % wound closure on the 10th day, surpassing AM extract at 63.7 %. In contrast, the control group achieved only 32.1 % closure. This comparative study underscores the distinct advantages of AM and Viola extracts in wound dressing applications. While AM presents specific strengths, Viola extract exhibits superior mechanical properties, antibacterial efficacy, and accelerated wound closure, suggesting its potential with significant clinical implications.

Synthesis and characterization of mupirocin-LDH/PVA nanofibrous composite as a dual-carrier drug release system

Nowadays, nanofibrous structures based on organic and inorganic materials are considered a drug delivery system for the controlled release of antibiotics and other antibacterial agents. The main goal of this research is a combination of the special properties of nanofibrous structure and Mupirocin-loaded Layered double hydroxide (LDH) to obtain a dual-carrier drug release system to provide long term antibacterial properties in wound healing process. Regards, unloaded layered double hydroxide (LDH) and Mupirocin-loaded LDH, which were synthesized by co-precipitation method, were added to Polyvinyl alcohol (PVA) solution in different mass ratio and electrospun using different processing conditions. The physico-chemical characterizations were performed using SEM, FTIR and tensile strength tests. The biological properties of the fabricated nanocomposites were evaluated using antibacterial test and in vitro cell culturing followed by MTT assay. The SEM results showed a bead-less and uniform morphology of nanofibrous composite containing Mupirocin(2.3 wt%)-LDH(15 wt%)/PVA with an average fiber diameter of about 270 ± 58 nm. According to the release study, the maximum release of the mupirocin drug was about 54 % in the first 6 h. The antibiogram analysis exhibited good antibacterial activity of mupirocin-loaded nanocomposite against both bacteria, especially gram-positive one. Finally, MTT assay approved the biocompatibility of the mupirocin-loaded nanocomposite. Overall, the produced nanofibrous composites would be a promising dual-carrier system for controlled release of antibiotic.

The role of hydrogels in the management of brain tumours: a narrative review.

Conventional therapeutic techniques for brain tumours have limitations and side effects, necessitating the need for alternative treatment options. MRI-monitored therapeutic hydrogel systems show potential as a non-surgical approach for brain tumour treatment. Hydrogels have unique physical and chemical properties that make them promising for brain tumour treatment, including the ability to encapsulate therapeutic agents, provide sustained and controlled drug release, and overcome the blood-brain barrier for better penetration. By combining hydrogel systems with MRI techniques, it is possible to develop therapeutic approaches that provide real-time monitoring and controlled release of therapeutic agents. Surgical resection remains important, but there is a growing need for alternative approaches that can complement or replace traditional methods. The objective of this comprehensive narrative review is to evaluate the potential of MRI-monitored therapeutic hydrogel systems in non-surgical brain tumour treatment.

Intelligent responsive self-assembled micro-nanocapsules: Used to delay gel gelation time

In the application of polymer gels to profile control and water shutoff, the gelation time will directly determine whether the gel can “go further” in the formation, but the most of the methods for delaying gel gelation time are complicated or have low responsiveness. There is an urgent need for an effective method for delaying gel gelation time with intelligent response. Inspired by the slow-release effect of drug capsules, this paper uses the self-assembly effect of gas-phase hydrophobic SiO2 in aqueous solution as a capsule to prepare an intelligent responsive self-assembled micro-nanocapsules. The capsule slowly releases the cross-linking agent under the stimulation of external conditions such as temperature and pH value, thus delaying gel gelation time. When the pH value is 2 and the concentration of gas-phase hydrophobic SiO2 particles is 10%, the gelation time of the capsule gel system at 30, 60, 90, and 120 °C is 12.5, 13.2, 15.2, and 21.1 times longer than that of the gel system without containing capsule, respectively. Compared with other methods, the yield stress of the gel without containing capsules was 78 Pa, and the yield stress after the addition of capsules was 322 Pa. The intelligent responsive self-assembled micro-nanocapsules prepared by gas-phase hydrophobic silica nanoparticles can not only delay the gel gelation time, but also increase the gel strength. The slow release of cross-linking agent from capsule provides an effective method for prolongating the gelation time of polymer gels.

Mix design optimisation of self-sealing concrete containing microcapsules with polyurethane shell and water repellent cargo

Despite the robust ability of microcapsules (MIC) to break and release agent for healing/sealing efficacy, the reduction of concrete strength has been a major issue when using MIC. In this study, the optimisation of concrete mix design was initiated with employing three main parameters: MIC size (56, 93 μm), MIC dosage (0, 3, 6% by weight of cement) and water-cement (w/c) ratio (0.40, 0.50, 0.60). The used microcapsules consisted of water repellent agent core acting as a sealing agent and polyurethane as the shell material. Results confirmed the MIC dosage as the most significant factor affecting the mechanical properties, while no significant effect on the MIC size. Further, the MIC effect can be reduced by changing the concrete mix design from low to high w/c. The sealing efficiency of concrete was remarkably improved with the inclusion of MIC and a good bond between the capsules and concrete matrix was attained.

Effect of Antimicrobial Agent Coating on Physicochemical and Biologic Properties of Implant Abutments: A Systematic Review.

To analyze the effectiveness of coating of abutments with antimicrobial agents and their influence on the physicochemical and biologic properties of the coated materials. This work was registered in Open Science Framework (osf.io/6tkcp) and followed the PRISMA protocols. A search of two independent reviewers of articles published up to October 29, 2021, was performed in the Embase, PubMed, Science Direct, and Scopus databases. The databases found a total of 1,474 references. After excluding the duplicates, 1,050 remained. After reading the titles and abstracts and applying the inclusion criteria, 13 articles remained and were read in full. A total of 8 articles were included in this systematic review. Different antimicrobial agents have been used to coat abutments, including graphene oxide, polydopamine, titanium and zirconium nitride, lactoferrin, tetracycline, silver, and doxycycline with varied release times. Titanium-coated silver showed a better antimicrobial agent release time of up to 28 days. Chemical analysis confirmed the presence of antimicrobials on the surface after coating. Different pathogenic microorganisms, such as Streptococcus sanguinis, Streptococcus oralis, and Staphylococcus aureus, were inhibited when in contact with the coated surface. This review showed that there is still no consensus on which is the better antimicrobial agent and which coated materials have the better performance. However, the association of surface coating of abutments with antimicrobials is feasible and can benefit many patients, which can support their clinical use to favor the healing process and prevent infections that can lead to treatment failure with dental implants.

Enhanced antifungal properties of poly(butylene succinate) film with lignin nanoparticles and trans-cinnamaldehyde for mango packaging

Sustainable poly(butylene succinate) (PBS) films incorporating lignin nanoparticles (LN) and trans-cinnamaldehyde (CN) have been developed to preserve mango freshness and provide food safety. PBS/LN, PBS/CN, and PBS/LN/CN composite films were produced by blown film melt extrusion. This study investigated the effect of CN-LN on the CN remaining content, thermal, mechanical, and barrier properties, diffusion coefficient, and antifungal activity of PBS films both in vitro and in vivo. Results showed that LN in the PBS/LN/CN composite film contained more CN than in the PBS/CN film. The compatibility of CN-LN with PBS produced homogeneous surfaces with enhanced barrier properties. PBS/LN/CN composite films demonstrated superior antifungal efficacy, inhibiting the growth of Colletotrichum gloeosporioides and preserving mango quality during storage. Results suggested that incorporating LN into PBS composite films prolonged the sustained release of antifungal agents, thereby inhibiting microbial growth and extending the shelf life of mangoes. Development of PBS/LN/CN composite films is a beneficial step toward reducing food waste and enhancing food safety.

Mucoadhesive Buccal Tablet Formulation of Azithromycin dihydrate for treatment of Upper Respiratory Tract Infection

The buccal drug delivery system is a versatile delivery system which can be designed for local or systemic effect. The objective of the study was to developed patient complacent tablet which can give sustain release of antibacterial agent for relief of upper respiratory tract infection. Azithromycin dihydrate is a semi-synthetic macrolide antibiotic widely used to prevent bacterial infections in the upper respiratory tract. The mucoadhesive buccal tablets of azithromycin dihydrate were formulated by varying concentrations of polymers (natural and synthetic), glidant and other excipients. The drug-excipient compatibility studies were carried out through DSC and FTIR studies. The selected excipients were found to be compatible. Further the dry blend of drug-excipients was evaluated for pre-compression properties. The prepared tablets were evaluated as per the general monograph for tablets of IP. The studies were also carried out to evaluate sustained release of the drug and mucoadhesivity of the tablets. A 23 level (2 level and 3 factors) factorial design was navigated to study the effect of natural, synthetic polymers and the glidant on mucoadhesive strength and percentage cumulative drug release at 8 hours. The responsive variables were analysed using ANOVA by Design-Expert version 12.0. It was concluded that these excipients significantly affected the response variables. The optimized tablet formulation was found to have an adequate mucoadhesion and a cumulative percentage release. The final product was performed for accelerated stability studies, optimized formulation was found to be stable at room temperature and accelerated temperature for three months.

한국어 직접 증거성의 1인칭 효과에 관한 단상

This article probes evidential characteristic of -te- and -ne, working on the constraint release of 1st person agent. Root sentences with direct evidentiality show the duplicity that the use of 1st person agent is sometimes restricted but eased other times. 1st person agent is objectified as if it were the 3rd person and escapes the restriction within the framework of evidentiality. There is not enough discussion on the evidential characteristics of -te- and -ne which affect this process. In this article we propose that -te-, -ne still invoke the direct eviden- tiality based on the fact that because of the non­eye­witness evidentaility the evidential strength of -te-, -ne do not undermine the assertiveness of evidential strength of proposition realized with direct evidentiality. This evidential effect works on 1st person agent constraint easing where, speaker objectifies 1st person agent who is protagonist of the event by reducing evidential effect of participatory evidentiality. The result of this note is expected to provide fundamental description to represent syntactic relation between -te-, -ne and 1st person agent.