Search Results (5,061)

In this study, a pH-responsive molecularly imprinted polymer (MIP) drug carrier was developed utilizing boric acid-functionalized mesoporous silica nanoparticles (MSNs) as the substrate. The carrier was engineered for controlled drug release, with capecitabine (CAPE) being selected as the template molecule due to its structural characteristics and clinical relevance. In vitro drug release studies demonstrated the pH-responsive release behaviors of the fabricated carrier, highlighting its promising applicability in the controlled release of pharmaceutical compounds containing cis-diols, particularly for site-specific therapy where pH variations serve as physiological triggers. Full article

The Caco-2 in vitro model of the intestinal barrier is a well-established system for the investigation of the intestinal fate of orally ingested chemicals and drugs, and it has been used for over ten years by pharmaceutical industries as a model for absorption in preclinical studies. The Caco-2 model shows a fair correlation with in vivo drug absorption, though some inherent biases remain unresolved. Its main limitation lies in the lack of structural complexity, as it does not replicate the diverse cell types and mucus layer present in the human intestinal epithelium. Consequently, the development of advanced in vitro models of the intestinal barrier, that more structurally resemble the human intestinal epithelium physiology, has increased the potential applications of these models. Recently, Caco-2-based advanced intestinal models have proven effective in predicting nanomaterial uptake and transport across the intestinal barrier. The aim of this review is to provide a state-of-the-art of human in vitro intestinal barrier models for the study of translocation/uptake of nanoparticles relevant for oral exposure, including inorganic nanomaterials, micro/nano plastic, and fiber nanomaterials. The main effects of the above-mentioned nanomaterials on the intestinal barrier are also reported. Full article

Appropriate carriers or templates are crucial for maintaining the stability, biological activity, and bioavailability of selenium nanoparticles (SeNPs). Selecting suitable templates remains challenging for fully utilizing SeNPs functionalities and developing applicable products. Exosome-like nanoparticles (ELNs) have gained importance in drug delivery systems, yet research on selenium products prepared using exosomes remains limited. To address this gap, we utilized Cyperus bean ELNs to deliver SeNPs, investigated three preparation methods for SeNPs-ELNs, identified the optimal approach, and performed characterization studies. Notably, all three methods successfully loaded SeNPs. Ultrasonic cell fragmentation is the optimal approach, achieving significant increases in selenium loading (5.59 ± 0.167 ng/μg), enlargement of particle size (431.17 ± 10.78 nm), and reduced absolute zeta potential (−4.1 ± 0.43 mV). Moreover, both exosome formulations demonstrated enhanced stability against aggregation during storage at 4 °C, while their stability varied with pH conditions. In vitro digestibility tests showed greater stability of SeNP-ELNs in digestive fluids compared to ELNs alone. Additionally, neither ELNs nor SeNP-ELNs exhibited cytotoxicity toward LO₂ cells, and the relative erythrocyte hemolysis remained below 5% at protein concentrations of 2.5, 7.5, 15, 30, and 60 μg/mL. Overall, ultrasonic cell fragmentation effectively loaded plant-derived exosomes with nano-selenium at high capacity, presenting new opportunities for their use as functional components in food and pharmaceutical applications. Full article

Concern over the presence of pharmaceutical waste in the environment has prompted research into the management of emerging organic micropollutants (EOMs). In response, sustainable technologies have been applied as alternatives to reduce the effects of these contaminants. This study investigated the capacity of filamentous fungi isolated from iron mine soil in the Amazon region to biodegrade the drug chloroquine diphosphate. An initial screening assessed the growth of four fungal strains on solid media containing chloroquine diphosphate: Trichoderma pseudoasperelloides CBMAI 2752, Penicillium rolfsii CBMAI 2753, Talaromyces verruculosus CBMAI 2754, and Penicillium sp. cf. guaibinense CBMAI 2758. Among them, Penicillium sp. cf. guaibinense CBMAI 2758 was selected for further testing in liquid media. A Box–Behnken factorial design was applied with three variables, pH (5, 7, and 9), incubation time (5, 10, and 15 days), and chloroquine diphosphate concentration (50, 75, and 100 mg·L⁻¹), totaling 15 experiments. The samples were analyzed by gas chromatography–mass spectrometry (GC-MS). The most effective conditions for chloroquine biodegradation were pH 7, 100 mg·L⁻¹ concentration, and 10 days of incubation. Four metabolites were identified: one resulting from N-deethylation M1 (N4-(7-chloroquinolin-4-yl)-N1-ethylpentane-1,4-diamine), two from carbon–carbon bond cleavage M2 (7-chloro-N-ethylquinolin-4-amine) and M3 (N1,N1-diethylpentane-1,4-diamine), and one from aromatic deamination M4 (N1-ethylbutane-1,4-diamine) by enzymatic reactions. The toxicity analysis showed that the products obtained from the biodegradation of chloroquine were less toxic than the commercial formulation of this compound. These findings highlight the biotechnological potential of Amazonian fungi for drug biodegradation and decontamination. Full article

Poly(organo)phosphazenes (PPZs) are increasingly recognized as versatile biomaterials for drug delivery applications in nanomedicine. Their unique hybrid structure—featuring an inorganic backbone and highly tunable organic side chains—confers exceptional biocompatibility and adaptability. Through precise synthetic methodologies, PPZs can be engineered to exhibit a wide spectrum of functional properties, including the formation of multifunctional nanostructures tailored for specific therapeutic needs. These attributes enable PPZs to address several critical challenges associated with conventional drug delivery systems, such as poor pharmacokinetics and pharmacodynamics. By modulating solubility profiles, enhancing drug stability, enabling targeted delivery, and supporting controlled release, PPZs offer a robust platform for improving therapeutic efficacy and patient outcomes. This review explores the fundamental chemistry, biopharmaceutical characteristics, and biomedical applications of PPZs, particularly emphasizing their role in zero-dimensional nanotherapeutic systems, including various nanoparticle formulations. PPZ-based nanotherapeutics are further examined based on their drug-loading mechanisms, which include electrostatic complexation in polyelectrolytic systems, self-assembly in amphiphilic constructs, and covalent conjugation with active pharmaceutical agents. Together, these strategies underscore the potential of PPZs as a next-generation material for advanced drug delivery platforms. Full article

High-mobility group box 1 (HMGB1) is a nuclear protein that can interact with a transmembrane cell surface receptor for advanced glycation end products (RAGEs) and mediates the inflammatory pathways that lead to various pathological conditions like cancer, diabetes, cardiovascular diseases, and neurodegenerative disorders. Blocking the HMGB1/RAGE axis using various small synthetic or natural molecules has been proven to be an effective therapeutic approach to treating these inflammatory conditions. However, the low water solubility of these pharmacoactive molecules limits their clinical use. Pharmaceutically active molecules with low solubility and bioavailability in vivo convey a higher risk of failure for drug development and drug innovation. The pharmacokinetic and pharmacodynamics parameters of these compounds are majorly affected by their solubility. Enhancement of the bioavailability and solubility of drugs is a significant challenge in the area of pharmaceutical formulations. This review mainly describes various technologies utilized to improve the bioavailability of synthetic or natural molecules which have been particularly used in various inflammatory conditions acting specifically through the HMGB1/RAGE pathway. Full article

Background/Objectives. This manuscript presents an overview of advances in oncological radiotherapy as an effective treatment method for cancerous tumors, focusing on mechanisms of action within metabolite–antimetabolite systems. The urgency of this topic is underscored by the fact that cancer remains one of the leading causes of death worldwide: as of 2022, approximately 20 million new cases were diagnosed globally, accounting for about 0.25% of the total population. Given prognostic models predicting a steady increase in cancer incidence to 35 million cases by 2050, there is an urgent need for the latest developments in physics, chemistry, molecular biology, pharmacy, and strict adherence to oncological vigilance. The purpose of this work is to demonstrate the relationship between the nature and mechanisms of past diagnostic and therapeutic oncology approaches, their current improvements, and future prospects. Particular emphasis is placed on isotope technologies in the production of therapeutic nuclides, focusing on the mechanisms of formation of simple and complex theranostic compounds and their classification according to target specificity. Methods. The methodology involved searching, selecting, and analyzing information from PubMed, Scopus, and Web of Science databases, as well as from available official online sources over the past 20 years. The search was structured around the structure–mechanism–effect relationship of active pharmaceutical ingredients (APIs). The manuscript, including graphic materials, was prepared using a narrative synthesis method. Results. The results present a sequential analysis of materials related to isotope technology, particularly nucleus stability and instability. An explanation of theranostic principles enabled a detailed description of the action mechanisms of radiopharmaceuticals on various receptors within the metabolite–antimetabolite system using specific drug models. Attention is also given to radioactive nanotheranostics, exemplified by the mechanisms of action of radioactive nanoparticles such as Tc-99m, AuNPs, wwAgNPs, FeNPs, and others. Conclusions. Radiotheranostics, which combines the diagnostic properties of unstable nuclei with therapeutic effects, serves as an effective adjunctive and/or independent method for treating cancer patients. Despite the emergence of resistance to both chemotherapy and radiotherapy, existing nuclide resources provide protection against subsequent tumor metastasis. However, given the unfavorable cancer incidence prognosis over the next 25 years, the development of “preventive” drugs is recommended. Progress in this area will be facilitated by modern medical knowledge and a deeper understanding of ligand–receptor interactions to trigger apoptosis in rapidly proliferating cells. Full article

Since its discovery in the late 19th century, spinal muscular atrophy (SMA) has had a significant medical and societal impact, primarily affecting newborns, toddlers, and young adults. While new pharmaceutical strategies are effective in treating SMA in a particular subset of patients, continued research is necessary to improve the well-being of patients. Treatments are needed for those who do not respond to newly approved drugs and older patients with significantly compromised neuron systems. After summarizing SMA genotypes, phenotypes, and approved pharmacological treatments, this review presents ongoing trials for approved and new molecules, new formulations, and administration methods. Based on the work of our lab, we also discuss nutritional interventions that aim to counteract the oxidative stress present in SMA cells. Finally, we assess rehabilitative interventions, focusing on psychological approaches. Full article

Background: Precision medicine refers to the formulation of personalized drug regimens according to the individual characteristics of patients to achieve optimal efficacy and minimize adverse reactions. Additive manufacturing (AM), also known as three-dimensional (3D) printing, has emerged as an optimal solution for precision drug delivery, enabling customizable and the fabrication of multifunctional structures with precise control over morphology and release behavior in pharmaceutics. However, the influence of 3D printing parameters on the printed tablets, especially regarding in vitro and in vivo performance, remains poorly understood, limiting the optimization of manufacturing processes for controlled-release profiles. Objective: To establish the fabrication process of 3D-printed controlled-release tablets via comprehensively understanding the printing parameters using fused deposition modeling (FDM) combined with hot-melt extrusion (HME) technologies. HPMC-AS/HPC-EF was used as the drug delivery matrix and carbamazepine (CBZ) was used as a model drug to investigate the in vitro drug delivery performance of the printed tablets. Methodology: Thermogravimetric analysis (TGA) was employed to assess the thermal compatibility of CBZ with HPMC-AS/HPC-EF excipients up to 230 °C, surpassing typical processing temperatures (160–200 °C). The formation of stable amorphous solid dispersions (ASDs) was validated using differential scanning calorimetry (DSC), hot-stage polarized light microscopy (PLM), and powder X-ray diffraction (PXRD). A 15-group full factorial design was then used to evaluate the effects of the fan speed (20–100%), platform temperature (40–80 °C), and printing speed (20–100 mm/s) on the tablet properties. Response surface modeling (RSM) with inverse square-root transformation was applied to analyze the dissolution kinetics, specifically t_50% (time for 50% drug release) and Q_4h (drug released at 4 h). Results: TGA confirmed the thermal compatibility of CBZ with HPMC-AS/HPC-EF, enabling stable ASD formation validated by DSC, PLM, and PXRD. The full factorial design revealed that printing speed was the dominant parameter governing dissolution behavior, with high speeds accelerating release and low speeds prolonging release through porosity-modulated diffusion control. RSM quadratic models showed optimal fits for t_50% (R² = 0.9936) and Q_4h (R² = 0.9019), highlighting the predictability of release kinetics via process parameter tuning. This work demonstrates the adaptability of polymer composite AM for tailoring drug release profiles, balancing mechanical integrity, release kinetics, and manufacturing scalability to advance multifunctional 3D-printed drug delivery devices in pharmaceutics. Full article

In the preceding and early stages of cancer progression, local drug delivery to pre-cancerous and cancerous skin lesions may be applied as an alternative or supplementary therapy. At present, 5-Fluorouracil, imiquimod, and tirbanibulin creams and ointments have established their place in practice, while several other active pharmaceutical ingredients (APIs) (e.g., calcipotriol, tretinoin, diclofenac) have been repurposed, used off-label, or are currently being investigated in mono- or combined chemotherapies of skin cancers. Apart from them, dozens to hundreds of therapeutics of natural and synthetic origin are proven to possess anti-tumor activity against melanoma, squamous cell carcinoma (SCC), and other skin cancer types in in vitro studies. Their clinical introduction is most often limited by low skin permeability, challenged targeted drug delivery, insufficient chemical stability, non-selective cytotoxicity, or insufficient safety data. A variety of prodrug and nanotechnological approaches, including vesicular systems, micro- and nanoemulsions, solid lipid nanoparticles, nanostructured lipid carriers, polymeric nanoparticles, and others, offer versatile solutions for overcoming the biophysical barrier function of the skin and the undesirable physicochemical nature of some drug molecules. This review aims to present the most significant aspects and latest achievements on the subject. Full article

Fused and spiro nitrogen-containing heterocycles play an important role as structural motifs in numerous biologically active natural products and pharmaceuticals. The review summarizes various approaches to the synthesis of three-, four-, five-, and six-membered fused and spiro heterocycles with one or two nitrogen atoms. The assembling of the titled compounds via cycloaddition, oxidative cyclization, intramolecular ring closure, and insertion of sextet intermediates—carbenes and nitrenes—is examined on a vast number of examples. Many of the reactions proceed with high regio-, stereo-, or diastereoselectivity and in excellent, up to quantitative, yield, which is of principal importance for the synthesis of chiral drug-like compounds. For most unusual and hardly predictable transformations, the mechanisms are given or referred to. Full article

The pharmaceutical industry faces significant challenges when promising drug candidates fail during development due to suboptimal ADME (absorption, distribution, metabolism, excretion) properties or toxicity concerns. Natural compounds are subject to the same pharmacokinetic considerations. In silico approaches offer a compelling advantage—they eliminate the need for physical samples and laboratory facilities, while providing rapid and cost-effective alternatives to expensive and time-consuming experimental testing. Computational methods can often effectively address common challenges associated with natural compounds, such as chemical instability and poor solubility. Through a review of the relevant scientific literature, we present a comprehensive analysis of in silico methods and tools used for ADME prediction, specifically examining their application to natural compounds. Whereas we focus on identifying the predominant computational approaches applicable to natural compounds, these tools were developed for conventional drug discovery and are of general use. We examine an array of computational approaches for evaluating natural compounds, including fundamental methods like quantum mechanics calculations, molecular docking, and pharmacophore modeling, as well as more complex techniques such as QSAR analysis, molecular dynamics simulations, and PBPK modeling. Full article

The popularity of bioactive compounds extracted from sea cucumbers is growing due to their wide application in the pharmaceutical industry, particularly in the development of drugs for neurological disorders. Different types of compounds, such as saponins, phenolic compounds, cerebrosides, and glucocerebrosides, are being studied intensively for their efficacy in assessing the treatment of neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and brain tumors, among others. Positive results have been observed in the upregulation in the content of p-CREB, p-PL3K, BDNF, SOD, and MDA. Furthermore, the neuroprotective mechanism of the compounds against Alzheimer’s disease revealed that suppressing the phosphorylation of tau protein by the PI3K/Akt/GSK3β pathway leads to improved synaptic plasticity and reduced nerve fiber tangles. This comprehensive review explores recent findings on the therapeutic potential of sea cucumber bioactives in the treatment of brain-related disorders. Full article