Explore the vast range of titles available.

Drug molecules transformed into nanoparticles or endowed with nanostructures with or without the aid of carrier materials are referred to as \"nanomedicines\" and can overcome some inherent drawbacks of free drugs, such as poor water solubility, high drug dosage, and short drug half-life in vivo. However, most of the existing nanomedicines possess the drawback of low drug-loading (generally less than 10%) associated with more carrier materials. For intravenous administration, the extensive use of carrier materials might cause systemic toxicity and impose an extra burden of degradation, metabolism, and excretion of the materials for patients. Therefore, on the premise of guaranteeing therapeutic effect and function, reducing or avoiding the use of carrier materials is a promising alternative approach to solve these problems. Recently, high drug-loading nanomedicines, which have a drug-loading content higher than 10%, are attracting increasing interest. According to the fabrication strategies of nanomedicines, high drug-loading nanomedicines are divided into four main classes: nanomedicines with inert porous material as carrier, nanomedicines with drug as part of carrier, carrier-free nanomedicines, and nanomedicines following niche and complex strategies. To date, most of the existing high drug-loading nanomedicines belong to the first class, and few research studies have focused on other classes. In this review, we investigate the research status of high drug-loading nanomedicines and discuss the features of their fabrication strategies and optimum proposal in detail. We also point out deficiencies and developing direction of high drug-loading nanomedicines. We envision that high drug-loading nanomedicines will occupy an important position in the field of drug-delivery systems, and hope that novel perspectives will be proposed for the development of high drug-loading nanomedicines.

Intrinsic immunosuppressive tumor microenvironment (ITM) and insufficient tumor infiltration of T cells severely impede the progress of glioblastoma (GBM) immunotherapy. In this study, it is identify that inhibiting the expression of glucose transporter 1 (GLUT1) can facilitate the prevention of lactate excretion from tumor glycolysis, which significantly alleviates the lactate‐driven ITM by reducing immunosuppressive tumor‐associated macrophages (TAMs) and regulatory T cells (Tregs). Simultaneously, the findings show that the generated inflammatory cytokine IFN‐γ during immune activation aggravates the immune escape by upregulating immune checkpoint programmed death‐ligand 1 (PD‐L1) in tumor cells and TAMs. Therefore, an injectable thermogel loaded with a GLUT1 inhibitor BAY‐876 and a PD‐1/PD‐L1 blocker BMS‐1 (Gel@B‐B) for dual‐regulation of metabolism and immunity of GBM is developed. Consequently, in situ injection of Gel@B‐B significantly delays tumor growth and prolongs the survival of the orthotopic GBM mouse model. By actively exposing tumor antigens to antigen‐presenting cells, the GBM vaccine combined with Gel@B‐B is found to significantly increase the fraction of effector T cells (Th1/CTLs) in the tumor microenvironment, thereby remarkably mitigating tumor recurrence long‐term. This study may provide a promising strategy for GBM immunotherapy. Intrinsic immunosuppressive tumor microenvironment and insufficient tumor infiltration of T cells severely impede the progress of glioblastoma (GBM) immunotherapy. Herein, an injectable thermogel loaded with a GLUT1 inhibitor and a PD‐1/PD‐L1 blocker is fabricated for dual‐regulating the metabolism/immunity of GBM mice. Further combined with GBM vaccines significantly increased tumor infiltration of effector T cells (Th1/CTLs), delayed tumor growth, and prolonged survival.

Stem cell exosomes are nanoscale membrane vesicles released from stem cells of various origins that can regulate signal transduction pathways between liver cells, and their functions in intercellular communication have been recognized. Due to their natural substance transport properties and excellent biocompatibility, exosomes can also be used as drug carriers to release a variety of substances, which has great prospects in the treatment of critical and incurable diseases. Different types of stem cell exosomes have been used to study liver diseases. Due to current difficulties in the treatment of acute liver failure (ALF), this review will outline the potential of stem cell exosomes for ALF treatment. Specifically, we reviewed the pathogenesis of acute liver failure and the latest progress in the use of stem cell exosomes in the treatment of ALF, including the role of exosomes in inhibiting the ALF inflammatory response and regulating signal transduction pathways, the advantages of stem cell exosomes and their use as a drug‐loading system, and their pre‐clinical application in the treatment of ALF. Finally, the clinical research status of stem cell therapy for ALF and the current challenges of exosome clinical transformation are summarized. Mesenchymal stem cell‐derived exosomes from different sources and their use as drug‐loading systems to repair acute liver failure induced by inflammation, autophagy, apoptosis, various cytokines and signaling pathways,etc.

Calcium carbonate has slowly paved its way into the field of nanomaterial research due to its inherent properties: biocompatibility, pH-sensitivity, and slow biodegradability. In our efforts to synthesize calcium carbonate nanoparticles (CSCaCO3NP) from blood cockle shells (Anadara granosa), we developed a simple method to synthesize CSCaCO3NP, and loaded them with gefitinib (GEF) and paclitaxel (PTXL) to produce mono drug-loaded GEF-CSCaCO3NP, PTXL-CSCaCO3NP, and dual drug-loaded GEF-PTXL-CSCaCO3NP without usage of toxic chemicals. Fourier-transform infrared spectroscopy (FTIR) results reveal that the drugs are bound to CSCaCO3NP. Scanning electron microscopy studies reveal that the CSCaCO3NP, GEF-CSCaCO3NP, PTXL-CSCaCO3NP, and GEF-PTXL-CSCaCO3NP are almost spherical nanoparticles, with a diameter of 63.9 ± 22.3, 83.9 ± 28.2, 78.2 ± 26.4, and 87.2 ± 26.7 (nm), respectively. Dynamic light scattering (DLS) and N2 adsorption-desorption experiments revealed that the synthesized nanoparticles are negatively charged and mesoporous, with surface areas ranging from ~8 to 10 (m2/g). Powder X-ray diffraction (PXRD) confirms that the synthesized nanoparticles are aragonite. The CSCaCO3NP show excellent alkalinization property in plasma simulating conditions and greater solubility in a moderately acidic pH medium. The release of drugs from the nanoparticles showed zero order kinetics with a slow and sustained release. Therefore, the physico-chemical characteristics and in vitro findings suggest that the drug loaded CSCaCO3NP represent a promising drug delivery system to deliver GEF and PTXL against breast cancer.

Liposomes have been considered promising and versatile drug vesicles. Compared with traditional drug delivery systems, liposomes exhibit better properties, including site-targeting, sustained or controlled release, protection of drugs from degradation and clearance, superior therapeutic effects, and lower toxic side effects. Given these merits, several liposomal drug products have been successfully approved and used in clinics over the last couple of decades. In this review, the liposomal drug products approved by the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) are discussed. Based on the published approval package in the FDA and European public assessment report (EPAR) in EMA, the critical chemistry information and mature pharmaceutical technologies applied in the marketed liposomal products, including the lipid excipient, manufacturing methods, nanosizing technique, drug loading methods, as well as critical quality attributions (CQAs) of products, are introduced. Additionally, the current regulatory guidance and future perspectives related to liposomal products are summarized. This knowledge can be used for research and development of the liposomal drug candidates under various pipelines, including the laboratory bench, pilot plant, and commercial manufacturing.

Formulating drugs into nanoparticles offers many attractive advantages over free drugs including improved bioavailability, minimized toxic side effects, enhanced drug delivery, feasibility of incorporating other functions such as controlled release, imaging agents for imaging, targeting delivery, and loading more than one drug for combination therapies. One of the key parameters is drug loading, which is defined as the mass ratio of drug to drug‐loaded nanoparticles. Currently, most nanoparticle systems have relatively low drug loading (<10 wt%), and developing methods to increase drug loading remains a challenge. This Minireview presents an overview of recent research on developing nanoparticles with high drug loading (>10 wt%) from the perspective of synthesis strategies, including post‐loading, co‐loading, and pre‐loading. Based on these three different strategies, various nanoparticle systems with different materials and drugs are summarized and discussed in terms of their synthesis methods, drug loadings, encapsulation efficiencies, release profiles, stabilities, and their applications in drug delivery. The advantages and disadvantages of these strategies are presented with an objective of providing useful design rules for future development of high‐drug‐loading nanoparticles. Loaded up: This Minireview presents an overview of recent research on developing nanoparticles with high drug loading (>10 wt%) from the perspective of synthesis strategies, including post‐loading, co‐loading, and pre‐loading. Based on these three different strategies, various nanoparticle systems with different materials and drugs are summarized, and the advantages and disadvantages of these strategies are discussed to provide useful design rules for the future development of high‐drug‐loading nanoparticles.

The metabolic activity of tumor cells leads to the acidification of the surrounding microenvironment, which provides new strategies for the application of nanotechnology in cancer therapy. Researchers have developed various types of pH-responsive nanomaterials based on the tumor acidic microenvironment. This review provides an in-depth discussion on the design mechanisms, drug-loading strategies, and application pathways of tumor acidic microenvironment-responsive nanodrug delivery systems. These materials trigger drug release upon reaching the tumor microenvironment, enhancing therapeutic targeting and reducing toxicity to healthy cells. pH-responsive nanomaterials include organic nanomaterials, inorganic nanomaterials, and composite nanomaterials. Additionally, this review outlines the drug-loading strategies, application prospects, and challenges of pH-responsive nanomaterials, aiming to promote the development and clinical translation of this field.

Extracellular vesicles (EVs) are nano-sized, natural, cell-derived vesicles that contain the same nucleic acids, proteins, and lipids as their source cells. Thus, they can serve as natural carriers for therapeutic agents and drugs, and have many advantages over conventional nanocarriers, including their low immunogenicity, good biocompatibility, natural blood – brain barrier penetration, and capacity for gene delivery. This review first introduces the classification of EVs and then discusses several currently popular methods for isolating and purifying EVs, EVs-mediated drug delivery, and the functionalization of EVs as carriers. Thereby, it provides new avenues for the development of EVs-based therapeutic strategies in different fields of medicine. Finally, it highlights some challenges and future perspectives with regard to the clinical application of EVs. Graphical Abstract Highlights Various current techniques for isolating extracellular vesicles are reviewed, and their advantages and disadvantages are compared. An overview of the strategies used for the modification of extracellular vesicles and their application as delivery systems or therapeutic agents in different diseases is provided. Several challenges in the clinical application of extracellular vesicles-based nanoplatforms are discussed, along with solutions for their implementation as a promising therapeutic tool.

This systematic review offers a comprehensive analysis of plant-derived extracellular vesicles (PDEVs) as emerging drug delivery systems, focusing on original research articles published between 2016 and 2024 that exclusively examine the use of PDEVs for drug delivery. After a rigorous search across multiple databases, 20 relevant studies out of 805 initial results were selected for analysis. This review systematically summarizes the critical data on PDEV components, isolation methods, and drug-loading techniques. It highlights the potential of PDEVs to significantly enhance drug safety and efficacy, reduce dosage and toxicity, and align drug development with sustainable and environmentally friendly biotechnological processes. This review also emphasizes the advantages of PDEVs over mammalian-derived vesicles, such as cost-effectiveness, higher yield, and reduced immunogenicity. Additionally, it explores the synergistic potential between encapsulated drugs and bioactive compounds naturally present in PDEVs. This study acknowledges the challenges in standardizing isolation and formulation methods for clinical use. Overall, this review provides valuable insights into the current state and future directions of PDEV-based drug delivery systems, highlighting their promising role in advancing pharmaceutical research and development.

Cancer treatment is currently one of the most critical healthcare issues globally. A well-designed drug delivery system can precisely target tumor tissues, improve efficacy, and reduce damage to normal tissues. Stimuli-responsive drug delivery systems (SRDDSs) have shown promising application prospects. Intelligent nano drug delivery systems responsive to endogenous stimuli such as weak acidity, complex redox characteristics, hypoxia, active energy metabolism, as well as exogenous stimuli like high temperature, light, pressure, and magnetic fields are increasingly being applied in chemotherapy, radiotherapy, photothermal therapy, photodynamic therapy, and various other anticancer approaches. Metal–organic frameworks (MOFs) have become promising candidate materials for constructing SRDDSs due to their large surface area, tunable porosity and structure, ease of synthesis and modification, and good biocompatibility. This paper reviews the application of MOF-based SRDDSs in various modes of cancer therapy. It summarizes the key aspects, including the classification, synthesis, modifications, drug loading modes, stimuli-responsive mechanisms, and their roles in different cancer treatment modalities. Furthermore, we address the current challenges and summarize the potential applications of artificial intelligence in MOF synthesis. Finally, we propose strategies to enhance the efficacy and safety of MOF-based SRDDSs, ultimately aiming at facilitating their clinical translation. Graphical Abstract