Search Results (99)

Background/Objectives: Advanced drug delivery systems (DDSs) are essential for targeted delivery, controlled release, and reduced systemic toxicity, but their clinical adoption is limited by biological barriers, manufacturing complexities, and cost. The aim of this systematic review is to critically evaluate the quantitative relationships between platform design, overcoming biological barriers, and clinical translation outcomes for DDS developed between 2016 and 2025. Methods: A comprehensive literature search was conducted in PubMed/MEDLINE, Scopus, and Web of Science (January 2016–April 2025) in accordance with the PRISMA 2020 guidelines. Included studies focused on experimental or clinical data for nanocarrier platforms (liposomes, lipid nanoparticles, polymer systems, biomimetic carriers, extracellular vesicles). Data on platform characteristics, interactions with barriers, pharmacokinetics, manufacturing, and clinical outcomes were extracted and synthesized in narrative form due to the significant methodological heterogeneity. Results: An analysis of 77 included studies confirms that successful clinical translation depends on matching the physicochemical properties of the carrier (size, surface chemistry, material) to specific biological barriers. Liposomes and lipid nanoparticles (LNPs) remain the most clinically validated platforms, exploiting the EPR effect and liver tropism, respectively. Key engineering solutions include stealth coatings, ligand-mediated targeting, and stimulus-responsive materials to overcome barriers such as mononuclear phagocyte system clearance, the blood–brain barrier, and mucosal barriers. Microfluidic and continuous manufacturing processes enable reproducibility, but scalability, cost, and immunogenicity (e.g., anti-PEG responses) remain key translational challenges. Engineered extracellular vesicles, biomimetic carriers, and 3D/4D-printed systems combined with AI-driven design demonstrate the potential for personalized, adaptive delivery. Conclusions: Cutting-edge DDSs have validated their clinical value, but realizing their full potential requires a holistic, patient-centered design approach integrating barrier-specific engineering, scalable manufacturing, and rigorous safety assessment from the earliest stages of development. Further progress will depend on standardizing methods for new platforms (e.g., extracellular vesicles), implementing digital and AI tools, and ensuring translational feasibility as a fundamental principle. Full article

Extracellular vesicles (EVs) are naturally occurring cell-derived vesicles that contain the same nucleic acids, proteins, and lipids as their source cells. These nano-sized systems, which are derived from a wide range of cell types within an organism and are present in all body fluids. EVs play a crucial role both in health and disease, particularly in cancer and neurodegenerative disorders. Due to their particular structure, they can function as natural carriers for therapeutic agents and drugs, akin to synthetic liposomes. EVs exhibit numerous advantages over conventional synthetic nanocarriers and other lipid-based delivery systems, including their favorable biocompatibility, natural blood–brain barrier penetration, and capacity for gene delivery. However, EVs’ complex characterization and standardization, as well as being more expensive than other vesicular systems, are major drawbacks that need to be addressed before drug loading. The present review introduces the classification of EVs and their physiological roles, currently popular methods for isolating and purifying EVs, the main therapeutic approaches of EV-mediated drug delivery, and the functionalization of EVs as carriers. Consequently, it establishes novel pathways for advancing EV-based therapeutic methodologies across diverse medical disciplines. The study concludes with a discussion of the new challenges and future perspectives related to the clinical application of EVs. Full article

The development of polymer-based systems is central to the design of next-generation drug delivery carriers, as polymers enable versatile tuning of physicochemical properties and responsiveness. In this work, we introduce a 3D printing-based strategy for the fabrication of multicompartment capsules that integrate multiple polymers within a unique one-step process. This approach allows precise spatial organization and structural complexity, yielding capsules with customizable features such as compartmentalization, polymer-specific responsiveness, and localized release control. In particular, pH-triggered release can be programmed across distinct polymeric regions of the capsules, enabling site-specific delivery along different intestinal segments, including the small intestine and colon. The use of 3D printing thus provides a scalable and adaptable platform to generate multifunctional polymer-based carriers with finely tunable drug release profiles, paving the way for new directions in polymer-enabled controlled delivery technologies. Full article

Background/Objectives: In this work, a series of six new indazole-benzimidazole hybrids (M1–M6) were designed, synthesized, and fully characterized. The design of these compounds was based on the combination of two pharmacophoric units, indazole and benzimidazole, both known for their broad spectrum of biological activities. Methods: The molecular hybridization strategy was planned to combine these scaffolds through an effective synthetic pathway, using 6-nitroindazole, two 2-mercaptobenzimidazoles, and 1,3- or 1,5-dihaloalkanes as key precursors, affording the desired hybrids in good yields and with enhanced biological activity. Quantum chemical calculations were performed to investigate the structural, electronic, and electrostatic properties of M1–M6 molecules using Density Functional Theory (DFT) at the B3LYP/6-311++G(d,p) level. The antimicrobial activity efficacy of these compounds was assessed in vitro against four Gram-positive bacteria (Staphylococcus aureus, Enterococcus faecalis, Bacillus cereus, and Lactobacillus plantarum), four Gram-negative bacteria (Salmonella enteritidis, Escherichia coli, Campylobacter coli, Campylobacter jejuni), and four fungal strains (Saccharomyces cerevisiae, Candida albicans, Candida tropicalis, and Candida glabrata) using ampicillin and tetracycline as reference standard drugs. Results: Among the series, compound M6 exhibited remarkable antimicrobial activity, with minimum inhibitory concentrations (MIC) of 1.95 µg/mL against S. cerevisiae and C. tropicalis, and 3.90 µg/mL against S. aureus, B. cereus, and S. enteritidis, while the standards Ampicillin (AmB) (MIC ≥ 15.62 µg/mL) and Tetracycline (TET) (MIC ≥ 7.81 µg/mL) exhibited higher MIC values. To gain molecular insights into the compounds, an in silico docking study was performed to determine the interactions of M1–M6 ligands against the antimicrobial target beta-ketoacyl-acyl carrier protein (ACP) synthase III complexed with malonyl-COA (PDB ID: 1HNJ). Molecular modeling data provided valuable information on the structure-activity relationship (SAR) and the binding modes influencing the candidate ligand-protein recognition. Amino acid residues, such as Arg249, located in the solvent-exposed region, were essential for hydrogen bonding with the nitro group of the 6-nitroindazole moiety. Furthermore, polar side chains such as Asn274, Asn247, and His244 participated in interactions mediated by hydrogen bonding with the 5-nitrobenzimidazole moiety of these compound series. Conclusions: The hybridization of indazole and benzimidazole scaffolds produced compounds with promising antimicrobial activity, particularly M6, which demonstrated superior potency compared to standard antibiotics. Computational and docking analyses provided insights into the structure–activity relationships, highlighting these hybrids as potential candidates for antimicrobial drug development. Full article

Alzheimer’s disease (AD) is a complex neurodegenerative disease. The pathogenesis of AD remains incompletely understood. It is characterized by a variety of neuropathological changes, including neuroinflammation, neuronal loss and synaptic damage. Multiple pathological changes make achieving good therapeutic effects with a single drug treatment difficult, and using multiple drugs for combination therapy is currently the most effective method. Currently, the mainstay drugs used for AD treatment are hydrophobic drugs, such as curcumin, donepezil, and resveratrol. Because hydrophobic drugs cannot dissolve in bodily fluids and often aggregate or precipitate, their efficacy is greatly reduced. Therefore, there is an urgent need for a drug carrier that can effectively load and continuously release drugs. However, currently, there are few drug carriers that can achieve efficient co-loading of multiple hydrophobic drugs. Therefore, three of two-dimensional imine covalent organic frameworks (COFs) with different monomers were synthesized through rational design and screening. These three synthesized COFs are simultaneously loaded with curcumin (CUR) and benzofurazan (BZ) to achieve combined therapy. The results indicate that among this series of synthesized COFs, the COF synthesized from 4,4′,4″-(1,3,5-Triazine-2,4,6-triyl) trianiline and benzene-1,3,5-tricarboxaldehyde (COF-TB) exhibits optimal hydrophobic drug-loading capacity, enabling effective co-loading of CUR and BZ (BC@COF-TB). After treatment with BC@COF-TB, the cognitive function of 5×FAD mice was significantly improved. The COF platform provides a new way to deliver hydrophobic drugs for AD treatment. Full article

Fucoidan is of considerable interest for the development of drug carriers. The inclusion of fucoidan allows calcium carbonate microparticles in the form of vaterite to acquire new properties, enabling their use in the immobilization of protein preparations. In this work, we investigated the properties of hybrid vaterite microparticles with fucoidan from Fucus vesiculosus obtained by co-precipitation and loaded with recombinant human lactoferrin from goats. The hybrid microparticles had a smaller diameter (3–4 µm), larger surface area (35–36 m²g⁻¹), smaller pore size (5–10 nm average), and more negative ζ-potential (−(11–13) mV) than the control vaterite microparticles. The incorporation of lactoferrin into the microparticles by co-precipitation in complex with fucoidan was greater than when the protein was adsorbed onto the hybrid microparticles. Microparticles with fucoidan and lactoferrin were stable in acidic environments, released both components over a prolonged period at pH 7.4, and possessed mucoadhesive properties and anticoagulant activity. The antibacterial properties of hybrid microparticles with fucoidan and lactoferrin against Bacillus subtilis were characterized. Microparticles of vaterite with fucoidan can serve as a platform for the microfabrication of effective means of delivering therapeutic proteins. Full article

Today, cathinone and its synthetic derivatives are among the most popular narcotics in the world. Their different cytotoxic activities on humans are increasingly and rapidly being published in forensic reports and the scientific literature. New studies demonstrate that these compounds target the apoptosis of some human cancer cell lines. These results could potentially open a new perspective for cathinones’ use as potential therapeutic agents. Even so, the psychostimulant effects of these compounds require testing their activity in the form of drug delivery systems. In our work, we report on the first theoretical studies concerning the potential use of functionalised carbon nanotubes (CNTs) as carriers in the targeted transport of cathinones. Using density functional theory (DFT), we predicted cathinone–CNT interaction energies in environments with different polarity, as well as the stability of complexes in simplified models of healthy and cancer tissue. The results of the current work provide first-step insights into cathinone–CNT non-covalent complex formation in neutral and acidified environments. This study may serve as the theoretical basis for further experimental works on the possibility of using cathinone–CNT complexes in targeted anticancer therapy. Full article

Sarcomas are very complex and clinically challenging mesenchymal tumors. Although the standard therapeutic approach has improved the 5-year survival rate, many patients experience local relapses and/or distant metastases. To improve patient outcome, new strategies need to be investigated. Immunotoxins (ITs) based on rRNA N-glycosylases (also named ribosome-inactivating proteins, RIPs) are promising tools for cancer therapy because, by combining rRNA-glycosylase’s high cytotoxicity with carrier selectivity, they can specifically eliminate target neoplastic cells. In the last few years, 3D models have been extensively used in cancer research, particularly for target-specific drug screening. This study aimed to evaluate the possibility of utilizing ribosome-inactivating protein (RIP)-containing ITs to selectively target TfR1-, EGFR1- and Her2-expressing sarcoma adherent cells (ACs), spheroids (SSs) and organoids (ORs). To compare Its’ efficacy and ability to induce apoptosis, we performed dose–response viability and caspase 3/7 activation assays on rhabdomyosarcoma and osteosarcoma ACs, SSs and ORs treated with Tf-IT, αEGFR1-IT and αHer2-IT. Our results indicate that, compared to the corresponding unconjugated RIPs, all ITs showed increased cytotoxicity in sarcoma ACs. Despite the increased complexity characterizing 3D models, the higher IC₅₀ differences between ITs and unconjugated RIPs were obtained in ORs, which appeared more resistant to the nonspecific killing of the RIPs than either the ACs or SSs, thus augmenting the therapeutic window between unconjugated and conjugated RIPs. IT induced a more delayed apoptosis in 3D compared to 2D models. Our results provide essential outcomes for the potential use of these RIP-based ITs as a therapeutic strategy to treat sarcoma. Full article

A new method of the design of stimuli-sensitive multiliposomal containers for encapsulation and controlled drug release is described. Despite quite a wide choice of pH-sensitive containers, there is still a considerable challenge to synthesize those that respond quickly to small variations in pH and release most of the encapsulated drug in a short time. The suggested AMS-containing multiliposomal complexes demonstrated an excellent rate of encapsulated substance release under altering the pH of the outer solution. To improve the efficiency of the delivery of bioactive compounds to target cells and to increase the therapeutic effect, pH-sensitive liposomes were concentrated on the surface of the carrier- PEG-coated cationic liposomes. A pH-sensitive ampholytic derivative of cholan-24-oic acid embedded into the membrane of anionic liposomes allowed the rapid release of the cargo in the areas of low pH, such as tumors, inflammation sites, etc. The diameter of the complexes was optimized for passive targeting and typically ranged from 250 to 400 nm. The biodegradability of liposomes ensured enzymatic destruction of the multiliposomal containers and their elimination from the body after performing their transport function. The multiliposomal complexes and products of their biodegradation demonstrated low cytotoxicity. The composition of multiliposomal complexes, in particular, the amount of PEGylated lipid in the bilayer, was estimated to provide a high speed of the cargo release upon changing the pH. The novel developed pH-sensitive containers show potential for biomedical applications. Full article

Background: The aim of this study was to investigate the radioprotective efficacy of polymer complexes constructed from amifostine (WR-2721) and poly(hydroxyoxyethylene phosphate)s with different molecular weights. The use of suitable polymers for the immobilization of radioprotective drugs is aimed at improving or obtaining important new properties. Methods: The radioprotective efficacy of the compounds was investigated by cytotoxicity and the survival of mouse embryonic fibroblasts MEF LIG4^+/+ and MEF LIG4^−/− cells irradiated with 2, 6 and 12 Gy in the presence of amifostine (WR-2721) and its polymer complexes. Results: The radioprotective efficacy of the polymer complexes constructed of amifostine (WR-2721) and poly(hydroxyoxyethylene phosphate)s with different molecular weights showed promising activity and dose regimens. Conclusions: Cytotoxicity studies for tested cell lines MEF LIG4^+/+ and MEF LIG4^−/− cells showed that the polymer complexes were not toxic when equivalent doses of the drug amifostine (WR-2721) were applied to the cells. Irradiated MEF LIG4^+/+ cells demonstrated an increase in the surviving fraction when pre-treated with 0.5–5 mM polymer complexes when equivalent doses of amifostine (WR-2721) were applied to the cells and irradiated. The radioprotective efficacy had increased when the cells MEF LIG4^+/+ were irradiated with 12 Gy. These findings demonstrate that poly(hydroxyoxyethylene phosphate)s are suitable carriers of the radioprotective drug amifostine (WR-2721). They further suggest that they may be interesting for researchers seeking new challenges in discovering advanced radioprotective active substances. Full article

Neutrophils, the most abundant white blood cells, play a dual role in cancer progression. While they can promote tumor growth, metastasis, and immune suppression, they also exhibit anti-tumorigenic properties by attacking cancer cells and enhancing immune responses. This review explores the complex interplay between neutrophils and the tumor microenvironment (TME), highlighting their ability to switch between pro- and anti-tumor phenotypes based on external stimuli. Pro-tumorigenic neutrophils facilitate tumor growth through mechanisms such as neutrophil extracellular traps (NETs), secretion of pro-inflammatory cytokines, and immune evasion strategies. They contribute to angiogenesis, tumor invasion, and metastasis by releasing vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs). Conversely, anti-tumor neutrophils enhance cytotoxicity by generating reactive oxygen species (ROS), promoting antibody-dependent cell-mediated cytotoxicity (ADCC), and activating other immune cells such as cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. Recent advances in neutrophil-based drug delivery systems have harnessed their tumor-homing capabilities to improve targeted therapy. Neutrophil-mimicking nanoparticles and membrane-coated drug carriers offer enhanced drug accumulation in tumors, reduced systemic toxicity, and improved therapeutic outcomes. Additionally, strategies to modulate neutrophil activity, such as inhibiting their immunosuppressive functions or reprogramming them towards an anti-tumor phenotype, are emerging as promising approaches in cancer immunotherapy. Understanding neutrophil plasticity and their interactions with the TME provides new avenues for therapeutic interventions. Targeting neutrophil-mediated mechanisms could enhance existing cancer treatments and lead to the development of novel immunotherapies, ultimately improving patient survival and clinical outcomes. Full article

In this study, we report the synthesis and characterization of aminated poly(methyl silsesquioxane)-based hydrogels ((AP/MS)SO-hydrogels) as potential enzyme-sensitive vehicles for antianemic drugs. The hydrogels were synthesized via sol–gel polymerization and functionalized with amine groups. Characterization techniques included Congo red assay, Brunauer–Emmett–Teller (BET) surface area analysis, scanning electron microscopy, elemental analysis, ¹³C NMR, ²⁹Si NMR, and ATR-FTIR spectroscopy and microscopy of hydrogels. The sorption of ferric chloride and ferrous D-gluconate, as well as complexes of ferrous D-gluconate with HPCD, was evaluated. Crosslinking of the gel with bifunctional agents was performed to create a new amide enzyme-sensitive bond, followed by infrared characterization of the crosslinked product. Trypsin-mediated degradation studies demonstrated the sensitivity of the hydrogel to enzymatic cleavage under model conditions. Iron release experiments in gastric and intestine-simulating media confirmed prolonged release. Overall, our findings suggest that aminated PMSSO-hydrogels hold promise as versatile and biocompatible carriers for targeted delivery of antianemic agents, warranting further exploration in preclinical and clinical applications. Full article

The relevance of active research lies in the need to develop new technologies to improve drug delivery methods for the effective treatment of wound healing. Additionally, the potential application of organogels in other areas of biomedicine, such as creating medical patches with controlled drug delivery, indicates a wide range of possibilities for using this technology. This study focuses on developing controlled drug delivery systems using organogels as carriers for ceftriaxone and ofloxacin. By selecting optimal formulations, organogels were created to immobilize the drugs, facilitating their effective and sustained release. The swelling behavior of the hydrogels was studied, showing a swelling coefficient between 16 and 32%, indicating their ability to absorb liquid relative to their weight. Drug release studies demonstrated that ceftriaxone was released 1.8 times slower than ofloxacin, ensuring a more controlled delivery. Microbiological tests confirmed that the organogels containing ofloxacin exhibited antimicrobial activity against Escherichia coli, Bacillus subtilis, and Staphylococcus aureus. However, it was a challenge to estimate activity for the model antibiotic ceftriaxone due to bacterial resistance to it. Organogel poly(vinyl alcohol) (PVA)-DMSO–alginate modifications with surfactant cetylpyridinium bromide led to the formation of a polyelectrolyte complex on the interphase, allowing further enhanced the prolonged release of the drugs. The research identified that the optimal compositions for sustained drug release were organogels with compositions PVA (10%)-PVP (1%) DMSO (50%) and PVA (10%)-DMSO (50%) formulations, illustrating the transparent nature of these organogels making them suitable for ophthalmological application. Various organogels compositions (PVA-DMSO, PVA-poly(vinylpyrrolidone)-DMSO, PVA-DMSO–alginate, PVA-DMSO-PLGA, PVA-DMSO–drug–surfactant) loaded with ceftriaxone, ofloxacin, and surfactant were prepared and characterized, highlighting their potential use in antibiotic patches for wound healing. These organogels illustrate promising results for localized treatment of infections in wounds, cuts, burns, and other skin lesions. Full article

To avoid the critical problems of effective drugs not being carried to their targeted cancers and their quantity and location not being sensed in situ, this work presents a completely new innovative strategy to achieve both smart cancer targeting (SCT) and super-sensitive sensing (SSS), where one drug carrier works for effective drug loading and release. Herein, malignant melanoma treatment is used as an example of reliable detection and effective therapy. We report two characteristic dumbbell-like nano-micelles and spherical-like nano-micelles of hyaluronan induced by the Eu³⁺/Tb³⁺ complexes for effective drug loading and release, respectively. These special Eu³⁺/Tb³⁺-loaded nano-micelles (marked as ENM and TNM) have strong and sharp red/green luminescence that can sensitively detect the malignant melanoma drug dacarbazine through changes in fluorescence intensity. Cytotoxicity experiments confirmed that both ENM and TNM are not toxic to normal cells at very high concentrations of 4 mM. However, when loaded with cancer drugs (D-ENM and D-ENM), they both killed cancer cells with more than 40% efficacy at this concentration. The in vivo experiments confirmed that D-ENM and D-TNM can effectively target cancer cells in tissue and effectively impede cancer growth. The detection limits of ENM and TNM in sensing cancer drugs can reach 0.456 μg/mL and 0.139 μg/mL, respectively. Therefore, the reported Eu³⁺/Tb³⁺-induced hyaluronan nano-micelles (ENM and TNM) are distinguished carriers of this cancer drug and excellent in situ sensors, and they have highly therapeutic effects with extremely low toxicity to normal cells. Full article

This study introduces novel CD44-targeted and redox-responsive nanoparticles (FNPs), proposed as doxorubicin (DOX) delivery devices for breast cancer. A cationized and redox-responsive Human Serum Albumin derivative was synthesized by conjugating Human Serum Albumin with cystamine moieties and then ionically complexing it with HA. The suitability of FNPs for cancer therapy was assessed through physicochemical measurements of size distribution (mean diameter of 240 nm), shape, and zeta potential (15.4 mV). Nanoparticles possessed high DOX loading efficiency (90%) and were able to trigger the drug release under redox conditions of the tumor environment (55% release after 2 h incubation). The use of the carrier increased the cytotoxic effect of DOX by targeting the CD44 protein. It was shown that, upon loading, the cytotoxic effect of DOX was enhanced in relation to CD44 protein expression in both 2D and 3D models. DOX@FNPs significantly decrease cellular metabolism by reducing both oxygen consumption and extracellular acidification rates. Moreover, they decrease the expression of proteins involved in the oxidative phosphorylation pathway, consequently reducing cellular viability and motility, as well as breast cancer stem cells and spheroid formation, compared to free DOX. This new formulation could become pioneering in reducing chemoresistance phenomena and increasing the specificity of DOX in breast cancer patients. Full article