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Mesenchymal stem cells (MSCs) are recruited by malignant tumor cells to the tumor microenvironment (TME) and play a crucial role in the initiation and progression of malignant tumors. This role encompasses immune evasion, promotion of angiogenesis, stimulation of cancer cell proliferation, correlation with cancer stem cells, multilineage differentiation within the TME, and development of treatment resistance. Simultaneously, extensive research is exploring the homing effect of MSCs and MSC‐derived extracellular vesicles (MSCs‐EVs) in tumors, aiming to design them as carriers for antitumor substances. These substances are targeted to deliver antitumor drugs to enhance drug efficacy while reducing drug toxicity. This paper provides a review of the supportive role of MSCs in tumor progression and the associated molecular mechanisms. Additionally, we summarize the latest therapeutic strategies involving engineered MSCs and MSCs‐EVs in cancer treatment, including their utilization as carriers for gene therapeutic agents, chemotherapeutics, and oncolytic viruses. We also discuss the distribution and clearance of MSCs and MSCs‐EVs upon entry into the body to elucidate the potential of targeted therapies based on MSCs and MSCs‐EVs in cancer treatment, along with the challenges they face. [ABSTRACT FROM AUTHOR]

Paper‐based electronics are emerging as a new class of technology with broad areas of application. Despite several efforts to fabricate new types of flexible electronic devices by screen printing of conductive paste, many of them are often nonbiodegradable, toxic, and expensive, limiting their practical use in bioresorbable paper‐based electronics. To address this need, a highly conductive and biodegradable bimodal conductive paste is developed using cost‐effective zinc‐based micro and nanoparticles with a facile low‐temperature sintering process compatible with paper substrates. The two‐step sintering process involves the removal of the insulating zinc oxide layer by spray coating acetic acid followed by a heat press sintering process to ensure the formation of highly packed and continuous metallic traces. The required conditions for the heat press sintering process are systematically studied using electrical, optical, and mechanical characterization techniques. The results of these investigations revealed an ultra‐packed microstructure with high electrical conductivity (0.5 × 105 S m−1) and low oxide content that is obtained with a heat press sintering setting of 220 °C for 60 s. Finally, as a proof of concept, the conductive paste with an optimized sintering process is used to fabricate a wearable wireless heater for remote‐controlled release of therapeutics. The controlled delivery of the system is validated in the practical and on‐demand delivery of antibiotics for eradicating commonly found bacteria such as Staphylococcus aureus in dermal wound infections. The biocompatibility of all the materials and manufacturing process is validated by NIH/3T3 fibroblast cells via MTT assay and live/dead staining. [ABSTRACT FROM AUTHOR]

Improved global access to novel age‐appropriate formulations for paediatric subsets, either of new chemical entities or existing drugs, is a priority to ensure that medicines meet the needs of these patients. However, despite regulatory incentives, the introduction to the market of paediatric formulations still lags behind adult products. This is mainly caused by additional complexities associated with the development of acceptable age‐appropriate paediatric medicines. This position paper recommends the use of a paediatric Quality Target Product Profile as an efficient tool to facilitate early planning and decision making across all teams involved in paediatric formulation development during the children‐centric formulation design for new chemical entities, or to repurpose/reformulate off‐patent drugs. Essential key attributes of a paediatric formulation are suggested and described. Moreover, greater collaboration between formulation experts and clinical colleagues, including healthcare professionals, is advocated to lead to safe and effective, age‐appropriate medicinal products. Acceptability testing should be a secondary endpoint in paediatric clinical trials to ensure postmarketing adherence is not compromised by a lack of acceptability. Not knowing the indications and the related age groups and potential dosing regimens early enough is still a major hurdle for efficient paediatric formulation development; however, the proposed paediatric Quality Target Product Profile could be a valuable collaborative tool for planning and decision making to expedite paediatric product development, particularly for those with limited experience in developing a paediatric product. [ABSTRACT FROM AUTHOR]

Porous organic frameworks (POFs) represent a significant subclass of nanoporous materials in the field of materials science, offering exceptional characteristics for advanced applications. Covalent organic frameworks (COFs), as a novel and intriguing type of porous material, have garnered considerable attention due to their unique design capabilities, diverse nature, and wide‐ranging applications. The unique structural features of COFs, such as high surface area, tuneable pore size, and chemical stability, render them highly attractive for various applications, including targeted and controlled drug release, as well as improving the sensitivity and selectivity of electrochemical biosensors. Therefore, it is crucial to comprehend the methods employed in creating COFs with specific properties that can be effectively utilized in biomedical applications. To address this indispensable fact, this review paper commences with a concise summary of the different methods and classifications utilized in synthesizing COFs. Second, it highlights the recent advancements in COFs for drug delivery, including drug carriers as well as the classification of drug delivery systems and biosensing, encompassing drugs, biomacromolecules, small biomolecules and the detection of biomarkers. While exploring the potential of COFs in the biomedical field, it is important to acknowledge the limitations that researchers may encounter, which could impact the practicality of their applications. Third, this paper concludes with a thought‐provoking discussion that thoroughly addresses the challenges and opportunities associated with leveraging COFs for biomedical applications. This review paper aims to contribute to the scientific community's understanding of the immense potential of COFs in improving drug delivery systems and enhancing the performance of biosensors in biomedical applications. [ABSTRACT FROM AUTHOR]

Atherosclerosis, a chronic disease associated with metabolism, poses a significant risk to human well‐being. Currently, existing treatments for atherosclerosis lack sufficient efficiency, while the utilization of surface‐modified nanoparticles holds the potential to deliver highly effective therapeutic outcomes. These nanoparticles can target and bind to specific receptors that are abnormally over‐expressed in atherosclerotic conditions. This paper reviews recent research (2018–present) advances in various ligand‐modified nanoparticle systems targeting atherosclerosis by specifically targeting signature molecules in the hope of precise treatment at the molecular level and concludes with a discussion of the challenges and prospects in this field. The intention of this review is to inspire novel concepts for the design and advancement of targeted nanomedicines tailored specifically for the treatment of atherosclerosis. [ABSTRACT FROM AUTHOR]

Nanomedicine has been developed to reduce or eliminate the side effects and toxicity upon systemic therapy of chemotherapeutic agents and to improve their therapeutic efficacy. However, the translation of non‐sized or nano‐encapsulated drugs is hampered by the low penetration and accumulation of engineered nanoparticles (NPs) in sites of tumors as well as their poor pharmacokinetics. This may be due to the synthetic structure of NPs and also complicated and unknown characteristics of the solid tumor microenvironment (TME). As a result, the TME is being better identified, and the interactions between NPs and the TME or human body are being discovered or predicted. These findings have led to the development of more biocompatible, intelligent, and controllable bio‐based nanoformulations that could overcome current barriers and provide sufficient drug delivery to the TME, as discussed in this paper. These formulations are designed to (i) modify the surface of NPs to improve blood circulation while reducing their off‐target accumulation and side effects in vivo, (ii) pass through the tumor vasculature by modulating or targeting angiogenesis, (iii) promote NPs distribution in solid tumor regions by applying biological/physical stimuli or extracellular matrix remodeling, and (iv) overcome the cell membrane barrier and other compartments of the cell by specific cell targeting to release the payload drug into the cytoplasm or nucleoplasm. [ABSTRACT FROM AUTHOR]

Older people are often affected by impaired organ and bodily functions resulting in multimorbidity and polypharmacy, turning them into the main user group of many medicines. Very often, medicines have not specifically been developed for older people, causing practical medication problems for them like limited availability of easy to swallow formulations, easy to open packaging and dosing instructions for enteral administration. In 2020, the European Medicines Agency (EMA) published a reflection paper 'Pharmaceutical development of medicines for use in the older population', which discusses how the emerging needs of an ageing European population can be addressed by medicines regulation. The paper intends to help industry to better consider the needs of older people during pharmaceutical/clinical medicines development by summarising data on the most relevant topics, providing early suggestions on how to move forward and prompting expert discussions and studies into knowledge gaps. Topics include patient acceptability, (dis)advantages of an administration route, formulation, dosage form, packaging, dosing device and user instruction. While the paper is directed at older people and the pharmaceutical industry, the reflections are also relevant to younger patients with similar disease‐related needs and of value to other stakeholders parties, e.g., healthcare professionals, academics, patients and caregivers, as the paper makes clear what can be expected from industry and where collaborative work is needed. This commentary provides an overview of the different steps in the development of the reflection paper, discusses points considered most controversial and/or subject to (multidisciplinary) expert discussions and indicates their value for real world clinical practice. [ABSTRACT FROM AUTHOR]

Electrospraying has emerged as a versatile technique in the pharmaceutical field due to its potential in drug delivery and formulation. With its advantages of cost‐effectiveness, reproducibility, ease of operation, and scalability, electrospraying offers numerous benefits for pharmaceutical applications. Notably, the production of nanoparticles using electrospraying provides unique properties, including small size, drug encapsulation capabilities, biocompatibility, and scalability. Electrospray nanoparticles have demonstrated significant promise in various drug delivery routes, such as oral and topical administration. These nanoparticles enhance drug stability, protection, and permeability, effectively overcoming limitations associated with these routes. Moreover, electrospray nanoparticles have proven valuable in targeted drug delivery, improving drug bioavailability and efficacy. Their ability to penetrate tissues and cells enables enhanced drug delivery to specific sites within the body. Additionally, electrospray nanoparticles can be tailored with targeting ligands or responsive components for controlled release and combination therapy, exhibiting successful applications in cancer treatment and neurological disorders. Therefore, electrospray nanoparticle technology shows great promise in biomedical applications, offering a versatile platform for targeted drug delivery and therapeutic interventions. This comprehensive review examines the various drug delivery applications of electrospraying and provides insights into its possibilities and challenges. The paper discusses the principles, methods, and parameters of electrospraying, while also exploring its use in fabricating drug delivery systems, addressing poorly soluble drugs. By synthesizing the findings from multiple studies, this review offers a comprehensive understanding of electrospraying's current state and potential in the pharmaceutical industry. [ABSTRACT FROM AUTHOR]

Noise‐induced hearing loss (NIHL) is a common outcome of excessive reactive oxygen species in the cochlea, and the targeted delivery of antioxidants to the inner ear is a potential therapeutic strategy. In this paper, a novel natural biomaterials‐derived multifunctional delivery system using silk fibroin‐polydopamine (PDA)‐composited inverse opal microcarriers (PDA@SFMCs) is presented for inner ear drug delivery and NIHL therapy. Due to their large specific surface area and interpenetrating nanochannels, PDA@SFMCs can rapidly load active biomolecules making them a convenient medium for the storage and delivery of such molecules. In addition, surface modification of PDA enables the microcarriers to remain in the round window niche, thus facilitating the precise local and directed delivery of loaded drugs. Based on these features, it is demonstrated here that n‐acetylcysteine‐loaded silk microcarriers have satisfactory antioxidant properties on cells and can successfully prevent NIHL in guinea pigs. These results indicate that the natural multifunctional silk microcarriers are promising agents for local inner ear drug delivery in the clinic. [ABSTRACT FROM AUTHOR]

Vitamins are crucial for sustaining life because they play an essential role in numerous physiological processes. Vitamin deficiencies can lead to a wide range of severe health issues. In this context, there is a need to administer vitamin supplements through appropriate routes, such as the oral route, to ensure effective treatment. Therefore, understanding the pharmacokinetics of vitamins provides critical insights into absorption, distribution, and metabolism, all of which are essential for achieving the desired pharmacological response. In this review paper, we present information on vitamin deficiencies and emphasize the significance of understanding vitamin pharmacokinetics for improved clinical research. The pharmacokinetics of several vitamins face various challenges, and thus, this work briefly outlines the current issues and their potential solutions. We also discuss the feasibility of enhanced nanocarrier‐based pharmaceutical formulations for delivering vitamins. Recent studies have shown a preference for nanoformulations, which can address major limitations such as stability, solubility, absorption, and toxicity. Ultimately, the pharmacokinetics of pharmaceutical dosage forms containing vitamins can impede the treatment of diseases and disorders related to vitamin deficiency. [ABSTRACT FROM AUTHOR]

Nanocrystals refer to materials with at least one dimension smaller than 100 nm, composing of atoms arranged in single crystals or polycrystals. Nanocrystals have significant research value as they offer unique advantages over conventional pharmaceutical formulations, such as high bioavailability, enhanced targeting selectivity and controlled release ability and are therefore suitable for the delivery of a wide range of drugs such as insoluble drugs, antitumor drugs and genetic drugs with broad application prospects. In recent years, research on nanocrystals has been progressively refined and new products have been launched or entered the clinical phase of studies. However, issues such as safety and stability still stand that need to be addressed for further development of nanocrystal formulations, and significant gaps do exist in research in various fields in this pharmaceutical arena. This paper presents a systematic overview of the advanced development of nanocrystals, ranging from the preparation approaches of nanocrystals with which the bioavailability of poorly water‐soluble drugs is improved, critical properties of nanocrystals and associated characterization techniques, the recent development of nanocrystals with different administration routes, the advantages and associated limitations of nanocrystal formulations, the mechanisms of physical instability, and the enhanced dissolution performance, to the future perspectives, with a final view to shed more light on the future development of nanocrystals as a means of optimizing the bioavailability of drug candidates. This article is categorized under:Therapeutic Approaches and Drug Discovery > Emerging TechnologiesNanotechnology Approaches to Biology > Nanoscale Systems in Biology [ABSTRACT FROM AUTHOR]

Photonic crystals are a new class of optical microstructure materials characterized by a dielectric constant that varies periodically with space and features a photonic bandgap. Inspired by natural photonic crystals such as butterfly scales, a series of artificial photonic crystals are developed for use in integrated photonic platforms, biosensing, communication, and other fields. Among them, colloidal photonic crystals (CPCs) have gained widespread attention due to their excellent optical properties and advantages, such as ease of preparation and functionalization. This work reviews the classification and self‐assembly principles of CPCs, details some of the latest biomedical applications of large‐area, high‐quality CPCs prepared using advanced self‐assembly methods, summarizes the existing challenges in CPC construction and application, and anticipates future development directions and optimization strategy. With further advancements, CPCs are expected to play a more critical role in biosensors, drug delivery, cell research, and other fields, bringing significant benefits to biomedical research and clinical practice. [ABSTRACT FROM AUTHOR]

Small‐scale robots offer significant potential in minimally invasive medical procedures. Due to the nature of soft biological tissues, however, robots are exposed to complex environments with various challenges in locomotion, which is essential to overcome for useful medical tasks. A single mini‐robot often provides insufficient force on slippery biological surfaces to carry medical instruments, such as a fluid catheter or an electrical wire. Here, for the first time, a team of millirobots (TrainBot) is reported to generate around two times higher actuating force than a TrainBot unit by forming a convoy to collaboratively carry long and heavy cargos. The feet of each unit are optimized to increase the propulsive force around three times so that it can effectively crawl on slippery biological surfaces. A human‐scale permanent magnetic set‐up is developed to wirelessly actuate and control the TrainBot to transport heavy and lengthy loads through narrow biological lumens, such as the intestine and the bile duct. The first electrocauterization performed by the TrainBot is demonstrated to relieve a biliary obstruction and open a tunnel for fluid drainage and drug delivery. The developed technology sheds light on the collaborative strategy of small‐scale robots for future minimally invasive surgical procedures. [ABSTRACT FROM AUTHOR]

Microneedle (MN) technology offers a powerful approach for transdermal delivery enabling painless injection and facilitating self‐administration without the need for professional assistance. However, the weak mechanical strength of MNs can lead to inefficient drug delivery and serious skin irritation if the MNs fracture during administration and leave fragments under the skin. Thus, the MNs need to be mechanically robust to avoid fracture during penetration through the skin while maintaining efficient drug delivery. Herein, the polymer‐based MNs with layer‐by‐layer (LbL) films of silica (SiO2) nanoparticles (NPs) and a polycation (poly(diallyldimethylammonium chloride) (PDADMAC)) followed by hydrothermal calcination are reinforced. The mechanical strength of the MNs is significantly improved after LbL assembly and shows lower threshold pressure to penetrate skins. Moreover, their drug loading and releasing properties are significantly enhanced due to an increase in the surface area and interfacial interaction. These SiO2 nanoparticle‐containing LbL thin films have great potential for the surface modification of 3D microstructured devices such as MNs, as evidenced by their enhanced mechanical strength and drug coating efficiency that result in a promising MN drug delivery model. [ABSTRACT FROM AUTHOR]

Funduscopic diseases, including diabetic retinopathy (DR) and age‐related macular degeneration (AMD), significantly impact global visual health, leading to impaired vision and irreversible blindness. Delivering drugs to the posterior segment of the eye remains a challenge due to the presence of multiple physiological and anatomical barriers. Conventional drug delivery methods often prove ineffective and may cause side effects. Nanomaterials, characterized by their small size, large surface area, tunable properties, and biocompatibility, enhance the permeability, stability, and targeting of drugs. Ocular nanomaterials encompass a wide range, including lipid nanomaterials, polymer nanomaterials, metal nanomaterials, carbon nanomaterials, quantum dot nanomaterials, and so on. These innovative materials, often combined with hydrogels and exosomes, are engineered to address multiple mechanisms, including macrophage polarization, reactive oxygen species (ROS) scavenging, and anti‐vascular endothelial growth factor (VEGF). Compared to conventional modalities, nanomedicines achieve regulated and sustained delivery, reduced administration frequency, prolonged drug action, and minimized side effects. This study delves into the obstacles encountered in drug delivery to the posterior segment and highlights the progress facilitated by nanomedicine. Prospectively, these findings pave the way for next‐generation ocular drug delivery systems and deeper clinical research, aiming to refine treatments, alleviate the burden on patients, and ultimately improve visual health globally. [ABSTRACT FROM AUTHOR]

Lipidic nanocarriers are a broad class of lipid‐based vectors with proven potential for packaging and delivering emerging nucleic acid therapeutics. An important early step in the clinical development cycle is large‐scale screening of diverse formulation libraries to assess particle quality and payload delivery efficiency. Due to the size of the screening space, this process can be both costly and time‐consuming. To address this, computational models capable of predicting clinically relevant physio‐chemical properties of dendrimer‐lipid nanocarriers, along with their mRNA payload delivery efficiency in human cells are developed. The models are then deployed on a large theoretical nanocarrier pool consisting of over 4.5 million formulations. Top predictions are synthesised for validation using cell‐based assays, leading to the discovery of a high quality, high performing, candidate. The methods reported here enable rapid, high‐throughput, in silico pre‐screening for high‐quality candidates, and have great potential to reduce the cost and time required to bring mRNA therapies to the clinic. [ABSTRACT FROM AUTHOR]

We describe in this work an evaluation of bundles of hollow mesoporous silicon nanotubes to facilitate transfection of HeLa cells using small interfering RNA designed to knock down expression of Enhanced Green Fluorescent Protein (eGFP). These experiments entail direct visualization of the nanotube bundles associated with the cells using both scanning electron microscopy (SEM) and confocal fluorescence imaging. These nanotube bundles are generated by surface modification of nanotube arrays with aminopropyl‐triethoxysilane (APTES), followed by their ultrasonication in water, to create the amine‐terminated structures capable of electrostatic conjugation of siRNA at an efficiency of 23%–50% (depending on initial siRNA concentration). Delivery and transfection to HeLa cells are verified by quantification of fluorescence imaging; an average percent knockdown of ∼50% eGFP is achieved. As nanoscale drug delivery vehicles are expected to be resorbed in clinical use, we also assess SiNT bundle degradation during the above in vitro timescale using scanning and transmission electron (TEM) microscopies. We conclude with a brief discussion of challenges and opportunities in future experiments involving this platform. [ABSTRACT FROM AUTHOR]

This paper focuses on the development of hollow starch nanoparticles (HSNPs) as promising carriers for poorly soluble drugs. A new and efficient method is presented, based on an in situ gas‐foaming/salt‐leaching process within individual starch nanoparticles prepared by a solvent displacement technique. Characterization using dynamic light scattering, transmission electron microscopy, and nitrogen adsorption/desorption analysis confirmed the successful preparation of HSNPs. Solid dispersion systems with piroxicam (PRX) as a model drug were formulated to evaluate HSNPs' potential as poorly water‐soluble drug carriers. Solid‐state properties, dissolution behavior and stability of PRX‐HSNPs solid dispersions were investigated. In vitro dissolution studies revealed that using hydrophilic HSNPs as carriers significantly improved the release of PRX. Solid‐state characterization showed that the main reason for the improved dissolution was the adsorption of PRX on the outer and inner surfaces of the HSNPs in an amorphous state. Stability studies demonstrated that the amorphous nature of loaded PRX remained unaffected even after 12 weeks of storage at 75 % relative humidity. Accordingly, the proposed HSNPs offer a promising alternative for the delivery of poorly water‐soluble drugs. In addition, the synthesis strategy demonstrated for HSNPs is easy, efficient and could be extended to the preparation of other hollow polymeric nanoparticles. [ABSTRACT FROM AUTHOR]

Since the advent of supporting matrices for biological applications, many types of drugs have been administered via various forms of conventional drug delivery preparations, such as pills, solutions, creams, suppositories, injected gels and so on. Key parameters to all these systems for effective drug delivery are controlled release for sustained periods, targeted delivery, and enhancements of drug stability and efficacy, all of which can be manipulated by using polymers. Given the important impact of the structures of the polymers on these parameters, this mini‐review gives a simple introduction to the requirements of drug delivery systems and surveys the synthetic pathways to a key polymer in this field, namely poly(lactic acid). We also review the preparation of block copolymers that incorporate poly(lactic acid), to expand and further develop its properties for drug delivery systems. It is hoped that this short teacherly and introductory review will provide a basic stepping‐stone to more in‐depth reviews and papers and enable an easy access to this fast growing field. © 2023 Society of Industrial Chemistry. [ABSTRACT FROM AUTHOR]

Aerogel‐based biomaterials are increasingly being considered for biomedical applications due to their unique properties such as high porosity, hierarchical porous network, and large specific pore surface area. Depending on the pore size of the aerogel, biological effects such as cell adhesion, fluid absorption, oxygen permeability, and metabolite exchange can be altered. Based on the diverse potential of aerogels in biomedical applications, this paper provides a comprehensive review of fabrication processes including sol‐gel, aging, drying, and self‐assembly along with the materials that can be used to form aerogels. In addition to the technology utilizing aerogel itself, it also provides insight into the applicability of aerogel based on additive manufacturing technology. To this end, how microfluidic‐based technologies and 3D printing can be combined with aerogel‐based materials for biomedical applications is discussed. Furthermore, previously reported examples of aerogels for regenerative medicine and biomedical applications are thoroughly reviewed. A wide range of applications with aerogels including wound healing, drug delivery, tissue engineering, and diagnostics are demonstrated. Finally, the prospects for aerogel‐based biomedical applications are presented. The understanding of the fabrication, modification, and applicability of aerogels through this study is expected to shed light on the biomedical utilization of aerogels. [ABSTRACT FROM AUTHOR]

Recently, neurological disorders have led to a growing global burden of fatalities and disabilities. The limited capacity for natural self‐regeneration poses a significant challenge in repairing nervous system injuries, which is closely related to the complex microenvironment and nonregenerative nature of neurons. Metal–organic frameworks (MOFs), with their distinctive structure and properties including high surface area, porosity, tunability, stimuli‐responsive behavior, biocompatibility, and biodegradability, stand as an auspicious platform for devising therapeutic strategies aiming at nerve regeneration and repair. By taking advantage of these characteristics, researchers have the opportunity to explore innovative methods including endogenous stimulation, magnetic response therapy, phototherapy, ultrasound therapy, and drug delivery systems for the treatment of neurological diseases. Moreover, MOFs‐based stem cell therapy also is developed to inhibit neuroinflammation and oxidative stress, promote axon growth, regulate stem cell differentiation, promote nerve regeneration, and finally restore the function of injured nerves. In this paper, the preparation strategy and biological characteristics of MOFs, highlighting their applications in repairing nerve injuries and treating neural stem cells is presented. Finally, an outlook on the future development and challenges in the field of neuroscience concerning MOFs is provided. [ABSTRACT FROM AUTHOR]

The development of sustainable drug delivery systems is very important in the field of pharmaceutical research and has many advantages over the usual methods of drug administration, including improving effectiveness, reducing side effects, and increasing patient compliance. Among various techniques, electrospraying as a voltage‐driven process has emerged as a promising technology for the fabrication of drug‐loaded nanoparticles. In recent years, the application of electrospray approach for drug release has been widely investigated. However, optimization of electrospray process parameters and development of mathematical models to predict drug release kinetics from microparticles are still challenging. To address these issues, a combination of Central Composite Design (CCD) and Response Surface Methodology (RSM) has been used. This paper focuses on the application of CCD‐RSM for modeling and optimization of doxorubicin (DOX)‐poly(caprolactone) (PCL)‐polyethylene glycol (PEG) microparticles prepared using electrospray method. Doxorubicin, a widely used anticancer drug, exhibits potent cytotoxicity against a wide range of cancers. PCL‐PEG microparticles are promising as drug carriers due to their biocompatibility, controlled release properties, and ability to protect the encapsulated drug from degradation. The CCD‐RSM approach allows systematic investigation and optimization of several formulation and process variables, including polymer concentration, PCL‐PEG weight ratio, and applied voltage on drug release behavior. In addition, the effect of rheology and electrical conductivity of polymer fluid on the size of particles obtained from electrospraying was investigated. The effect of adding folic acid and doxorubicin in the optimized sample of nanoparticles and the effect of different concentrations of doxorubicin were investigated, and SEM, DLS, and FTIR techniques were used to characterize the microparticles, and the MMT test was performed to evaluate their cytotoxicity. The results showed that the optimized formulation is effective for sustained drug release over a long period for drug delivery applications. [ABSTRACT FROM AUTHOR]

Metal nanoparticles having magnetic properties are exciting for application in the directed transport of anticancer drugs encapsulated in them. To ensure drug‐loading capacity and controlled release, surface modification with host molecules is a fascinating choice. In this paper, we report the synthesis and surface modification of magnetic cobalt metal nanoparticles with oligosaccharide host molecules (β‐cyclodextrin) tethered on the surface. A β‐cyclodextrin‐folate derivative is synthesized and characterized using Infrared‐, Nuclear Magnetic Resonance‐, and Matrix‐Assisted Laser Deposition Ionization‐Time of Flight mass spectrometry. The size of the cobalt nanoparticles carrying the host molecule on the surface is ~10 nm. The nanoparticles are characterized using X‐Ray Diffraction, Transmission Electron Microscopy, particle size analyzer, Energy‐Dispersive X‐ray, and X‐ray Photoelectron Spectroscopy. The bare magnetic nanoparticles also show a strong saturation magnetization of 142.21 emu g−1. The chemotherapeutic drug 5‐fluorouracil is loaded on the surface‐modified cobalt nanoparticles through host: guest complexation mode and its controlled release is measured in‐vitro. The slow release is spread over more than 14 days, and a complete release of the loaded therapeutic cargo is not reached. The release is pH‐dependent and changes with acidic levels of the medium. The anticancer activity of the drug‐loaded nanocarrier on MDA‐MB‐231 (breast cancer) cells is investigated. The mechanism of cell death is studied, and the cells are found inhibited in the synthesis phase. Flow cytometric analysis shows that 79.70 % of the empty nanocarrier‐treated and 74.86 % 5‐fluorouracil‐loaded nanocarrier‐treated MDA‐MB‐231 cells were in the early apoptosis phase. This new combination nanocarrier is intriguing owing to its structural and magnetic properties, and the action on cell lines. [ABSTRACT FROM AUTHOR]

To liberate society from its dependence on fossil‐based fuels and materials it is pivotal to explore components of renewable plant biomass in applications that benefit from their intrinsic biodegradability, safety, and sustainability. Lignin, a byproduct of the pulp and paper industry, is a plausible material for carrying various types of cargo in small‐ and large‐scale applications. Herein, possibilities and constraints regarding the physical–chemical properties of the lignin source as well as modifications and processing required to render lignins suitable for the loading and release of pesticides, pharmaceuticals, and biological macromolecules is reviewed. In addition, the technical challenges, regulatory and toxicological aspects, and future research needed to realize some of the promises that nano‐ and microscaled lignin materials hold for a sustainable future are critically discussed. [ABSTRACT FROM AUTHOR]

New generations of vaccines have been developed by encapsulating messenger ribonucleic acid (mRNA) in lipid nanoparticle (LNP) carriers. In addition to the physicochemical properties of LNPs, the encapsulation efficiency (EE) of mRNA in LNPs is a key factor to screen vaccine assembly assays. Fluorescent dyes with amplified signals upon binding with mRNA are at the core of developing assays to quantify EE. However, disregarding the temporal effects during the assay impacts the accuracy of the assay. Here, the kinetics of temporal decay in fluorescence intensity of dye‐RNA complex—in Ribogreen assay—are reported and shown how this dynamic process can be impeded in the presence of a nonionic surfactant. Further, the impact of this dynamic process on the calculated EE is studied. The corrections needed to accurately assay dynamic mRNA loading processes are presented. [ABSTRACT FROM AUTHOR]

Developing time‐sustained drug delivery systems is a main goal in innovative medicines. Inspired by the architecture of secretory granules from the mammalian endocrine system it has generated non‐toxic microscale amyloid materials through the coordination between divalent metals and poly‐histidine stretches. Like their natural counterparts that keep the functionalities of the assembled protein, those synthetic structures release biologically active proteins during a slow self‐disintegration process occurring in vitro and upon in vivo administration. Being these granules formed by a single pure protein species and therefore, chemically homogenous, they act as highly promising time‐sustained drug delivery systems. Despite their enormous clinical potential, the nature of the clustering process and the quality of the released protein have been so far neglected issues. By using diverse polypeptide species and their protein‐only oligomeric nanoscale versions as convenient models, a conformational rearrangement and a stabilization of the building blocks during their transit through the secretory granules, being the released material structurally distinguishable from the original source is proved here. This fact indicates a dynamic nature of secretory amyloids that act as conformational arrangers rather than as plain, inert protein‐recruiting/protein‐releasing granular depots. [ABSTRACT FROM AUTHOR]

New advancements in nanocarrier technologies are revolutionizing the delivery of drugs through the skin, allowing for precise treatment with better absorption, stability, and bioavailability. This review investigates lipid and inorganic nanocarriers like liposomes, ethosomes, and inorganic nanoparticles and assesses their potential for delivering drugs through the skin. It emphasizes the mechanisms that enable controlled release and deeper skin penetration, which are crucial for ensuring effectiveness in clinical applications. The review synthesizes existing research, acknowledging that only few nanocarriers are successfully deployed in clinical settings. By offering a comprehensive overview, it sheds light on the progress and future obstacles to using nanocarriers for drug delivery through the skin. [ABSTRACT FROM AUTHOR]

Senescence is a heterogenous and dynamic process in which various cell types undergo cell‐cycle arrest due to cellular stressors. While senescence has been implicated in aging and many human pathologies, therapeutic interventions remain inadequate due to the absence of a comprehensive set of biomarkers in a context‐dependent manner. Polyphenols have been investigated as senotherapeutics in both preclinical and clinical settings. However, their use is hindered by limited stability, toxicity, modest bioavailability, and often inadequate concentration at target sites. To address these limitations, nanocarriers such as polymer nanoparticles and lipid vesicles can be utilized to enhance the efficacy of senolytic polyphenols. Focusing on widely studied senolytic agents—specifically fisetin, quercetin, and resveratrol—we provide concise summaries of their physical and chemical properties, along with an overview of preclinical and clinical findings. We also highlight common signaling pathways and potential toxicities associated with these agents. Addressing challenges linked to nanocarriers, we present examples of senotherapeutic delivery to various cell types, both with and without nanocarriers. Finally, continued research and development of senolytic agents and nanocarriers are encouraged to reduce the undesirable effects of senescence on different cell types and organs. This review underscores the need for establishing reliable sets of senescence biomarkers that could assist in evaluating the effectiveness of current and future senotherapeutic candidates and nanocarriers. [ABSTRACT FROM AUTHOR]

Biomolecule‐incorporated metal‐organic frameworks (b‐MOFs) exhibit enhanced bioavailability and biocompatibility, making them an ideal option for use as drug delivery vehicles. While b‐MOFs possess outstanding drug loading and release capabilities, their microscale crystal sizes restrict their applicability as nanocarriers and drug delivery systems. To overcome this limitation, this paper presents a microwave‐irradiation‐based technique for the synthesis of porous adenine‐incorporated Zn‐based MOFs with particle sizes of approximately 200 nm as paclitaxel nanocarriers. The nanomaterial demonstrated a substantial paclitaxel loading capacity of 637 mg g−1. Moreover, it effectively increased the solubility of paclitaxel by 2.5‐fold compared to that of the free form. Thus, the nano MOF is a promising delivery vehicle for paclitaxel. Notably, the paclitaxel‐loaded nano MOF exhibited higher toxicity toward cancer cells than the free drug, further highlighting its potential as an effective anticancer agent. [ABSTRACT FROM AUTHOR]

Background: Photodynamic therapy (PDT) has been widely accepted in keratocyte carcinoma and an increasing number of literatures concerning PDT in skin cancer is published. But a detailed examination of publication patterns of PDT in skin cancer has not yet been carried out. Methods: Bibliographies were retrieved from Web of Science Core Collection restricted the publication date from January 1, 1985 to December 31, 2021. The search terms were photodynamic therapy and skin cancer. Visualization analysis and statistical analysis were performed by VOSviewer (Version 1.6.13), R software (Version 4.1.2) and Scimago Graphica (Version 1.0.15). Results: 3248 documents were selected for analysis. The results showed that the number of annual publications related to PDT in skin cancer was gradually increased and would continue to increase in the future. The results illustrated that "melanoma", "nanoparticles", "drug‐delivery", "mechanism", "delivery" and "in‐vitro" are newly occurred topics. The most prolific country was the United States and the most productive institution was the University of Sao Paulo in Brazil. German researcher Szeimies RM published the most papers related to PDT in skin cancer. British Journal of Dermatology was the most popular journal in this field. Conclusion: The topic that PDT in skin cancer is a heated issue. Our study revealed the bibliometric result of the field, which might provide the prospects for further research. We recommend future investigations focusing on PDT in treating melanoma, innovation of photosensitizer, improvement of drug delivery and the mechanism of PDT in skin cancer. [ABSTRACT FROM AUTHOR]

Background: Ferritin, a ubiquitously distributed iron storage protein, can specifically target tumor cells through transferrin receptor 1. Due to its rearrangeable nanocage structure, ferritin can be loaded with anticancer drugs. Combined with amino acid modifications on the outer- and/or inner-spaces of the nanocage, ferritins can be further coupled with antigens, antibodies, and nucleotide sequences. Since ferritin is naturally presented in the human body, when used in vivo, ferritin exhibits good biocompatibility, and no immunogenic response occurs. These makes ferritin an ideal nanocarrier which shows broad application prospects in cancer therapy. Methods: In this study, to find articles, a search was made in PubMed with the keywords ferritin, drug delivery, drug delivery, and cancer treatment. Results: According to the investigation, some studies suggest that ferritin can be loaded with drugs and targeted for delivery to tumor tissue. Therefore, ferritin nanocarriers loaded with drugs can be used in chemotherapy, photodynamic therapy (PDT), photothermal therapy (PTT) and immunotherapy. Importantly, the specific targeting of ferritin nanocarriers to tumor cells increases the effectiveness of related therapies and reduces side effects. Conclusions: We conclude in this paper that the superior properties of ferritin nanocarriers as an emerging drug delivery system make them a promising cancer treatment strategy. In the future, it is worth conducting clinical trials to further investigate the safety and efficacy of ferritin nanocarriers in patients. [ABSTRACT FROM AUTHOR]

While autoregulative adaptation is a common feature of living tissues, only a few feedback-controlled adaptive biomaterials are available so far. This paper herein reports a new polymer hydrogel platform designed to release anti-inflammatory molecules in response to the inflammatory activation of human blood. In this system, anti-inflammatory peptide drugs, targeting either the complement cascade, a complement receptor, or cyclophilin A, are conjugated to the hydrogel by a peptide sequence that is cleaved by elastase released from activated granulocytes. As a proof of concept, the adaptive drug delivery from the gel triggered by activated granulocytes and the effect of the released drug on the respective inflammatory pathways are demonstrated. Adjusting the gel functionalization degree is shown to allow for tuning the drug release profiles to effective doses within a micromolar range. Feedback-controlled delivery of covalently conjugated drugs from a hydrogel matrix is concluded to provide valuable safety features suitable to equip medical devices with highly active anti-inflammatory agents without suppressing the general immunosurveillance. [ABSTRACT FROM AUTHOR]

In the present paper, biodegradable hybrid hydrogels were prepared by using chitosan as a natural polymer and polyurethane containing azomethine as a synthetic polymer for the drug delivery application for 5‐fluorouracil. The fabricated hydrogels were characterized via FT‐IR and SEM analysis. Besides, the thermal, mechanical, and wettability properties, water uptake, biodegradation, protein absorption, drug loading, and release behaviors of the hybrid hydrogels were studied. The obtained results indicated that the fabricated hybrid hydrogels have exhibited good mechanical, hydrophilic, water uptake, and biodegradation behaviors. The hybrid hydrogels also showed 50% drug release amounts and they could be a good candidate for the controlled delivery of 5‐FU due to these properties. [ABSTRACT FROM AUTHOR]

The evolving landscape of personalized medicine necessitates a shift from traditional therapeutic interventions towards precision‐driven approaches. Embracing this paradigm, our research probes the therapeutic efficacy of the aqueous crude extract (ACE) of Calocybe indica in cervical cancer treatment, merging botanical insights with advanced molecular research. We observed that ACE exerts significant influences on nuclear morphology and cell cycle modulation, further inducing early apoptosis and showcasing prebiotic attributes. Characterization of ACE have identified several phytochemicals including significant presence of octadeconoic acid. Simultaneously, utilizing advanced Molecular Dynamics (MD) simulations, we deciphered the intricate molecular interactions between Vascular Endothelial Growth Factor (VEGF) and Octadecanoic acid to establish C.indica's role as an anticancer agent. Our study delineates Octadecanoic acid's potential as a robust binding partner for VEGF, with comprehensive analyses from RMSD and RMSF profiles highlighting the stability and adaptability of the protein–ligand interactions. Further in‐depth thermodynamic explorations via MM‐GBSA calculations reveal the binding landscape of the VEGF–Octadecanoic acid complex. Emerging therapeutic innovations, encompassing proteolysis‐targeting chimeras (PROTACs) and avant‐garde nanocarriers, are discussed in the context of their synergy with compounds like Calocybe indica P&C. This convergence underscores the profound therapeutic potential awaiting clinical exploration. This study offers a holistic perspective on the promising therapeutic avenues facilitated by C. indica against cervical cancer, intricately woven with advanced molecular interactions and the prospective integration of precision therapeutics in modern oncology. [ABSTRACT FROM AUTHOR]

Clinical deployment of oligonucleotides requires delivery technologies that improve stability, target tissue accumulation and cellular internalization. Exosomes show potential as ideal delivery vehicles. However, an affordable generalizable system for efficient loading of oligonucleotides on exosomes remain lacking. Here, we identified an Exosomal Anchor DNA Aptamer (EAA) via SELEX against exosomes immobilized with our proprietary CP05 peptides. EAA shows high binding affinity to different exosomes and enables efficient loading of nucleic acid drugs on exosomes. Serum stability of thrombin inhibitor NU172 was prolonged by exosome-loading, resulting in increased blood flow after injury in vivo. Importantly, Duchenne Muscular Dystrophy PMO can be readily loaded on exosomes via EAA (EXOEAA-PMO). EXOEAA-PMO elicited significantly greater muscle cell uptake, tissue accumulation and dystrophin expression than PMO in vitro and in vivo. Systemic administration of EXOEAA-PMO elicited therapeutic levels of dystrophin restoration and functional improvements in mdx mice. Altogether, our study demonstrates that EAA enables efficient loading of different nucleic acid drugs on exosomes, thus providing an easy and generalizable strategy for loading nucleic acid therapeutics on exosomes. Synopsis: This study identifies an exosome-binding DNA aptamer (Exosomal Anchor Aptamer—EAA) and demonstrates that EAA binds to exosomes of different origins effectively and enables efficient loading of different nucleic acid drugs on exosomes. This study provides an easy generalizable strategy for loading nucleic acid therapeutics on exosomes orthogonal to CD63-binding peptides, which are better suited for protein and peptide loading. EAA showed high binding affinity to exosomes irrespective of origin. EAA enabled loading of different nucleic acid drugs on exosomes, with thrombin DNA aptamer inhibitor NU172 loaded on exosomes extended the serum stability. Duchenne Muscular Dystrophy (DMD) phosphorodiamidate morpholino oligomers (PMOs) were efficiently loaded on exosomes via EAA to form EXOEAA-PMO and systemic administration EXOEAA-PMO at low doses improved muscle function and pathologies in dystrophic mice. This study identifies an exosome-binding DNA aptamer (Exosomal Anchor Aptamer - EAA) and demonstrates that EAA binds to exosomes of different origins effectively and enables efficient loading of different nucleic acid drugs on exosomes. This study provides an easy generalizable strategy for loading nucleic acid therapeutics on exosomes orthogonal to CD63-binding peptides, which are better suited for protein and peptide loading. [ABSTRACT FROM AUTHOR]

This paper aims to give an overview of our current research and development on hot‐melt extrusion (HME) for pharmaceutical formulation and drug delivery. Unfortunately, a large percentage of marketed drugs (40%) and those in the development pipeline (90%) are poorly water soluble. We use a few examples to show that solubility of APIs can be drastically improved by using HME to mix them with different biocompatible polymers and playing with the various process parameters (extrusion temperature, screw speed, screw configuration, etc.). The advantages of this technique are then presented as well as the further development needed to make this process fully industrial for pharmaceutical purposes. [ABSTRACT FROM AUTHOR]

Conventional microneedles (MNs) are designed as an array of micrometer‐sized projections that can painlessly penetrate the skin. Fabrication of MN arrays can be costly and time‐consuming; additionally, full penetration of an array of MNs with ten to thousands of projections into the skin may not be achievable. This paper reports a new design of MNs known as microblades (MBs) which consist of a singular microstructure. The single integrated design of the MBs reduces the fabrication cost and time, facilitates more effective penetration, and may pave the way for the scale‐up manufacturing of MN devices. Different designs of MBs are fabricated by two‐photon polymerization technique, followed by polydimethylsiloxane micromolding and soft embossing to create replicas. The mechanical integrity of the designs is determined by a series of compression tests. Skin insertion and drug diffusion studies are conducted using a custom‐made applicator to insert the MBs into the porcine abdominal skin to demonstrate delivery of fluorescein tracer. MBs insertion and penetration capabilities and the diffusion of a model drug into a multi‐layered human skin are demonstrated using finite element analysis and 3D diffusion models. The results demonstrate the functional capabilities of the MBs as an alternative to MN arrays. [ABSTRACT FROM AUTHOR]

Hydroxyapatite/tricalcium phosphate (HA/β‐TCP) has been widely studied as a drug carrier, but the drug loading and release rate of the composites with different morphology significantly vary. In this paper, needle‐shaped, rod‐shaped, and ordered porous HA/β‐TCP composite was prepared by chemical co‐precipitation method, and ibuprofen (IBU) was used as a drug model to study the sustained‐release properties of IBU in vitro. The results showed that morphology of the HA/β‐TCP composite had a significant effect on the drug loading of IBU. The IBU loading of the ordered porous composite was as high as 101.3 mg/g, which was 2.2 times and 3.46 times higher than that of the rod‐shaped and needle‐shaped composite to IBU, respectively. The drug release test of IBU showed that the release rate of the ordered porous HA/β‐TCP to IBU was slower than that of the rod‐shaped and needle‐shaped composite in the initial 10 h, and reached the drug release equilibrium after the subsequent 30 h. The cumulative release of the ordered porous HA/β‐TCP composite to IBU reached 83.79 %, which was significantly smaller than that of the needle‐shaped and the rod‐shaped, showing better slow‐release performance for IBU. The ordered porous HA/β‐TCP composite have great application potential in quantitative drug delivery systems. [ABSTRACT FROM AUTHOR]

This paper deals with the development of polymeric nanocarriers based on amphiphilic copolymers of N‐vinyl‐2‐pyrrolidone and acrylic acid of various molecular weights synthesized through the AIBN‐initiated radical copolymerization of N‐vinyl‐2‐pyrrolidone and acrylic acid in the presence of n‐octadecyl mercaptan. The structure of the copolymers is characterized by 1Н NMR, 13С NMR, IR and MALDI‐TOF MS spectroscopy. It is shown that the length of the hydrophilic block defines the size of the nanoaggregates while impacting the steric stabilization efficiency and the probability of the interchain hydrogen bond formation. The hydrogen bonds formation between the residues of N‐vinyl‐2‐pyrrolidone and acrylic acid is in agreement with the reduction of the ζ‐potential of the nanoaggregates and the critical aggregation concentrations upon increasing the molecular weight. The presence of acrylic acid residues in the amphiphilic macromolecules leads to a higher affinity for doxorubicin and slow partial release of doxorubicin bonded with the aggregates' corona, which is helpful for reducing its cardiac toxicity. Nanoaggregates with a paclitaxel‐loaded hydrophobic core are obtained, showing the possibility of dual loading. The amphiphilic copolymers of N‐vinyl‐2‐pyrrolidone and acrylic acid containing an n‐octadecyl thio end group are thus promising candidates for combination cancer therapy with immobilized anti‐cancer drugs, paclitaxel, and doxorubicin. [ABSTRACT FROM AUTHOR]

The incidence and lethal rate of cancers are rapidly rising recently, however current treatments of cancers, such as surgical resection, radiotherapy, chemotherapy and targeted therapy, usually require long treatment period and have more side effects and high recurrence rate. Enzyme‐powered micro/nanomotors (EMNMs), with powerful self‐propulsion, enhanced permeability and good biocompatibility, have shown great potential in crossing biological barrier and targeted drug transportation for cancer treatment; moreover, advanced approaches based on EMNMs such as photothermal therapy and starvation therapy have also been widely explored in cancer treatment. Although there are several review works discussing the progress of micro/nanomotors for biomedical applications, there is not one review paper with the focus on the cancer treatment based on EMNMs. Therefore, in this review, we try to concisely and timely summarize the recent progress of cancer treatment based on enzyme‐driven micro/nanomotors, such as brain tumors, bladder cancer, breast cancer and others. Finally, the challenges and outlook of cancer therapy based on EMNMs are discussed, hoping to provide fundamental guidance for the future development. [ABSTRACT FROM AUTHOR]

Stimulus‐sensitive drug delivery materials are of vital significance to modern therapeutic technology. In particular, glucose‐responsive hydrogels capable of biomimetic release of hypoglycemic drugs according to glucose concentrations are one of the current research hotspots. In this paper, an injectable, glucose‐induced disintegrated natural‐polysaccharide‐based hydrogel with good self‐healing ability and biocompatibility is reported. The glucose‐responsiveness of the hydrogel stems from the reversible phenylborate ester bonds. The glucose‐triggered disintegration and insulin release are demonstrated in the hydrogel in a physiological environment. The two polymers produced by the disintegration of the hydrogel have good biocompatibility and biodegradability. Therefore, the hydrogel is considered to result in the development of smart insulin delivery systems. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Inspired by the adaptation of cells to the surrounding environment, the combination of cell membrane and nanomaterials has gradually become a new type of biomimetic nanocomposite. The construction of endogenous membrane biomimetic nanocarriers (EMBNs) not only retains the structure of membrane surface protein, but also has the properties of nanoparticles (NPs), also provides the ability of natural interaction between nanomaterials and organisms, thus overcoming the severe challenges faced by traditional nanodelivery systems in clinical application. In this paper, the construction methods of EMBNs are reviewed, focusing on a simple method to prepare membrane proteins. Secondly, EMBNs were classified according a variety of cell membranes. Finally, the unique advantages of EMBNs in nanomedicine are introduced, including improving biocompatibility, homologous targeting ability, prolonging blood circulation time and immune escape ability. In nanomedicine, such as targeted delivery, phototherapy, immunotherapy and tumor imaging, multifaceted biological interfaces through membrane masking provide a new approach for the development of multifunctional NPs. [ABSTRACT FROM AUTHOR]

The stimuli‐responsiveness of injectable hydrogel has been drastically developed for the controlled release of drugs and has achieved encouraging curative effects in a variety of diseases including wounds, cardiovascular diseases, and tumors. The gelation, swelling, and degradation of such hydrogels respond to endogenous biochemical factors (such as pH, reactive oxygen species, glutathione, enzymes, glucose) and/or to exogenous physical stimulations (like light, magnetism, electricity, and ultrasound), thereby accurately releasing loaded drugs in response to specifically pathological status and as desired for treatment plan, and thus improving therapeutic efficacy effectively. This paper gives a detailed introduction of recent progresses in responsive injectable hydrogels and focuses on the design strategy of various stimuli‐sensitivities and their resultant alteration of gel dissociation and drug liberation behavior. Their application in disease treatment is also discussed. [ABSTRACT FROM AUTHOR]

Deregulated inflammations induced by various factors are one of the most common diseases in people's daily life, while severe inflammation can even lead to death. Thus, the efficient treatment of inflammation has always been the hot topic in the research of medicine. In the past decades, as a potential biomaterial, stimuli‐responsive hydrogels have been a focus of attention for the inflammation treatment due to their excellent biocompatibility and design flexibility. Recently, thanks to the rapid development of nanotechnology and material science, more and more efforts have been made to develop safer, more personal and more effective hydrogels for the therapy of some frequent but tough inflammations such as sepsis, rheumatoid arthritis, osteoarthritis, periodontitis, and ulcerative colitis. Herein, from recent studies and articles, the conventional and emerging hydrogels in the delivery of anti‐inflammatory drugs and the therapy for various inflammations are summarized. And their prospects of clinical translation and future development are also discussed in further detail. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are naturally occurring nanoparticles released from all eucaryotic and procaryotic cells. While their role was formerly largely underestimated, EVs are now clearly established as key mediators of intercellular communication. Therefore, these vesicles constitute an attractive topic of study for both basic and applied research with great potential, for example, as a new class of biomarkers, as cell‐free therapeutics or as drug delivery systems. However, the complexity and biological origin of EVs sometimes complicate their identification and therapeutic use. Thus, this rapidly expanding research field requires new methods and tools for the production, enrichment, detection, and therapeutic application of EVs. In this review, we have sought to explain how polymer materials actively contributed to overcome some of the limitations associated to EVs. Indeed, thanks to their infinite diversity of composition and properties, polymers can act through a variety of strategies and at different stages of EVs development. Overall, we would like to emphasize the importance of multidisciplinary research involving polymers to address persistent limitations in the field of EVs. [ABSTRACT FROM AUTHOR]

The alignment of anisotropic nanoparticles in flow has been used for a range of applications such as the preparation of strong fibres and the assembly of in‐plane aligned 1D‐nanoobjects that are used for electronic devices, sensors, energy and biological application. Important is also the flow behaviour of nanoparticles that were designed for nanomedical applications such as drug delivery. It is widely observed that non‐spherical nanoparticles have longer circulation times and a more favourable biodistribution. To be able to understand this behaviour, researchers have turned to analyzing the flow of non‐spherical nanoparticles in the blood stream. In this review, an overview of microfluidic techniques that are used to monitor the alignment of anisotropic nanoparticles in solution will be provided, which includes analysis by small angle X‐ray scattering (SAXS) and polarized light microscopy. The flow of these nanoparticles in blood is then discussed as the presence of red blood cells causes margination of some nanoparticles. Using fluorescence microscopy, the extent of margination can be identified, which coincides with the ability of nanoparticles to adhere to the cells grown along the wall. While these studies are mainly carried out in vitro using blood, initial investigations in vivo were able to confirm the unusual flow of anisotropic nanoparticles. [ABSTRACT FROM AUTHOR]

Lipid‐based nanostructures have garnered considerable interests over the last two decades, and have achieved tremendous clinical success including the first clinical approval of a liposome (Doxil) for cancer therapy in 1995 and the recent COVID‐19 mRNA lipid nanoparticle vaccines. Compared to liposomes which have a lipid bilayer surrounding an aqueous core, lipid nanoparticles with a particle structure have several attractive advantages for encapsulating poorly water‐soluble drugs such as better stability due to the particle structure, high drug encapsulation efficiency because of a pre‐ or co‐drug‐loading strategy. While many studies have reported the synthesis of lipid nanoparticles for hydrophobic drug encapsulation, the precise control of drug loading and encapsulation efficiency remains a significant challenge. This work reports a new concentration‐controlled nanoprecipitation platform technology for fabricating lipid nanoparticles with tunable drug loading up to 70 wt%. This method is applicable for encapsulating a wide range of drugs from very hydrophobic to slightly hydrophilic. Using this facile method, nanoparticles with tunable drug loading exhibited excellent properties such as small particle size, narrow size distribution, good particle stability, showing great promise for future drug delivery applications. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICI), pembrolizumab and atezolizumab, were recently approved for treatment‐refractory triple‐negative breast cancer (TNBC), where those with Programmed death‐ligand 1 (PD‐L1) positive early‐stage disease had improved responses. ICIs are administered systemically in the clinic, however, reaching effective therapeutic dosing is challenging due to severe off‐tumor toxicities. As such, intratumoral (IT) injection is increasingly investigated as an alternative delivery approach. However, repeated administration, which sometimes is invasive, is required due to rapid drug clearance from the tumor caused by increased interstitial fluid pressure. To minimize off‐target drug biodistribution, we developed the nanofluidic drug‐eluting seed (NDES) platform for sustained intratumoral release of therapeutic via molecular diffusion. Here we compared drug biodistribution between the NDES, intraperitoneal (IP) and intratumoral (IT) injection using fluorescently labeled PD‐L1 monoclonal antibody (αPD‐L1). We used two syngeneic TNBC murine models, EMT6 and 4T1, that differ in PD‐L1 expression, immunogenicity, and transport phenotype. We investigated on‐target (tumor) and off‐target distribution using different treatment approaches. As radiotherapy is increasingly used in combination with immunotherapy, we sought to investigate its effect on αPD‐L1 tumor accumulation and systemic distribution. The NDES‐treated cohort displayed sustained levels of αPD‐L1 in the tumor over the study period of 14 days with significantly lower off‐target organ distribution, compared to the IP or IT injection. However, we observed differences in the biodistribution of αPD‐L1 across tumor models and with radiation pretreatment. Thus, we sought to extensively characterize the tumor properties via histological analysis, diffusion evaluation and nanoparticles contrast‐enhanced CT. Overall, we demonstrate that ICI delivery via NDES is an effective method for sustained on‐target tumor delivery across tumor models and combination treatments. [ABSTRACT FROM AUTHOR]

Melittin, the principal constituent in bee venom, is an attractive candidate for cancer therapy. However, its clinical applications are limited by hemolysis, nonspecific cytotoxicity, and rapid metabolism. Herein, a novel genetically engineered vesicular antibody‐melittin (VAM) drug delivery platform was proposed and validated for targeted cancer combination therapy. VAM generated from the cellular plasma membrane was bio‐synthetically fabricated, with the recombinant protein (hGC33 scFv‐melittin) being harbored and displayed on the cell membrane. The bioactive and targetable nanomelittin conjugated by hGC33 scFv could be released in an MMP14‐responsive manner at tumor sites, which reduced off‐target toxicity, especially the hemolytic activity of melittin. Importantly, VAM could be loaded with small‐molecule drugs or nanoparticles for combination therapy. Nanomelittin formed pores in membranes and disturbed phospholipid bilayers, which allowed the anticancer agents (i.e., chemotherapeutic drug doxorubicin and sonosensitizer purpurin 18 nanoparticles) co‐delivered by VAM to penetrate deeper tumor sites, leading to synergistic therapeutic effects. In particular, the punching effect generated by sonodynamic therapy further improved the immunomodulatory effect of nanomelittin to activate the immune response. Taken together, our findings indicate that clinically translatable VAM‐based strategies represent a universal, promising approach to multimodal synergetic cancer therapy. [ABSTRACT FROM AUTHOR]

The main purpose herein is to provide an up‐to‐date review on noninvasive biomimetic, bioinspired, and bioengineered drug delivery system (DDS). Noninvasive DDS is an ever‐growing field critical for the applicability of drugs. It offers noninvasive administration routes with improved controlled, targeted, and triggered drug delivery. Noninvasive DDS employ many approaches and strategies, such as, nano‐ and microparticles, lipid‐based systems, sonophoresis, electrophoresis and iontophoresis, penetration enhancers, microneedles, and gels. The last decade seen a surge in research papers employing the paradigms of biomimicry, bioinspiration, and bioengineering. However, since the use of these terms in noninvasive DDS field is often inconsistent and unclear, some generalized perspectives are provided on the possible usage of these terms in future publications. Additionally, a critical discussion on the novelty and origins of these paradigms is provided. The advantages and disadvantages of each of the noninvasive routes and their current main limitations are summarized. The main aspects of indicated fields are discussed: The unique physiology of the related tissues, the main hurdles for mass transport, the various DDS tested, and materials selection. Finally, the basic concepts and therapeutic effects of these DDS are discussed and future venues for noninvasive biomimetic, bioinspired, and bioengineered DDS research are proposed. [ABSTRACT FROM AUTHOR]