Search Results (1,899)

Oxidative stress plays a crucial role in chronic nasal disorders, contributing to inflammation, tissue damage, and impaired mucosal function, highlighting the need for targeted therapies. Recent advancements in nasal drug delivery systems have expanded their applications for treating respiratory and inflammatory conditions. Among these, hydrogel-based systems offer prolonged release of active pharmaceutical ingredients (APIs), enhancing therapeutic efficacy and reducing dosing frequency. This study initially evaluates the antioxidant, anti-inflammatory, antimicrobial, and cytotoxic properties of Nanotriphala, followed by its incorporation into a thermoresponsive in situ hydrogel system, which was subsequently developed and characterized as a novel formulation. Nanotriphala exhibited >90% cell viability and significantly reduced nitric oxide (NO) levels by 40.55 µg/mL at 250 µg/mL. The hydrogel was characterized by key parameters, including viscosity, gelling time, pH, gelling temperature, texture analysis, and ex vivo spreadability. Stability was assessed under various conditions, and mutagenicity and antimutagenicity were evaluated using the Ames test. Results showed that the hydrogel gelled at 34 °C, exhibited good spreadability (10.25 ± 0.28 cm), a viscosity of 227 ± 22 cP, and maintained a pH of 5.75 ± 0.01, with optimal hardness and adhesiveness suitable for nasal application. It demonstrated antimicrobial activity against E. coli, P. aeruginosa, S. aureus, and S. epidermidis at minimal bactericidal concentrations (MBCs) of 32, 2, 4, and 8 µg/mL, respectively, with low mutagenicity (mutagenic index < 2) and strong antimutagenic activity (>60%). The gallic acid content was 0.5796 ± 0.0218 µg/100 mL. Stability studies confirmed optimal storage at 4 °C. These findings suggest that in situ hydrogel loaded with Nanotriphala is a promising nasal drug delivery system for managing oxidative stress and related inflammatory conditions. Full article

Background/Objectives: Oral mucositis (OM) is a common and debilitating side effect of cancer therapy, characterized by ulceration or inflammation of the oral mucosa. This study evaluates the preclinical efficacy of curcumin-loaded bicosome systems (cur-BS) in mitigating chemotherapy-induced OM in mice. Methods: BS were prepared using a combination of 1,2-di-palmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-dihexanoyl-sn-glycero-3-phosphocholine (DHPC), α-tocopherol, and curcumin, encapsulated within liposomal vesicles. Three formulations with different curcumin concentrations (180, 540, and 900 μM) were characterized by particle size, polydispersity index (PDI), encapsulation efficiency (EE), appearance, and morphology. The formulation with the highest concentration (cur-BS 5×) was selected for ex vivo permeability studies, release profile analysis, and in vitro anti-inflammatory efficacy. OM was induced in mice using 5-fluorouracil (5-FU) and acetic acid. Cur-BS 5× was compared to the commercial product Dentoxol^®. Results: The results showed that cur-BS 5× provided sustained release through a mechanism involving both diffusion and matrix relaxation, enhancing curcumin retention in deeper skin layers. Treatment with cur-BS 5× downregulated the expression of inflammatory markers (IL-1β and TNF-α). Macroscopic assessments demonstrated that both cur-BS 5× and Dentoxol^® reduced OM severity, with the greatest improvement observed between days 6 and 9. By day 24, OM scores were 1.25 ± 0.5 for cur-BS 5× and 1.0 ± 0.0 for Dentoxol^®, indicating effectiveness in both treatments. However, histological analysis revealed superior tissue recovery with cur-BS 5×, showing better epithelial structure and reduced inflammation. Cur-BS 5×-treated mice also exhibited greater weight recovery and higher survival rates compared to the Dentoxol^® group. Conclusions: These findings suggest that cur-BS 5× may enhance OM treatment, offering outcomes comparable to or better than those of Dentoxol^®. Full article

Existing dosimeters for radiation therapy are typically large, and their performance in in vivo system applications has not been assessed. This study develops a compact real-time dosimeter using silicon photomultipliers, plastic scintillators, and optical fibers and evaluates its in vivo applicability for radiation therapy. Dose calibration, dose-rate dependency and linearity, and short-term repeatability tests were conducted using solid water phantoms and bolus materials, and in vivo dosimetry was performed using an in-house phantom. The characterization evaluation results showed high linearity, with a coefficient of determination of 0.9995 for dose rates of 100–600 monitoring units (MU)/min, confirming an error rate within 2% when converted to dosage. In the short-term repeatability tests, the dosimeter exhibited good characteristics, with relative standard deviation (RSD) values lower than 2% for each beam delivery and an RSD value of 0.03% over ten beam deliveries. Dose measurements using the phantom indicated an average error rate of 3.83% compared to the values calculated using the treatment planning system. These results demonstrate a performance comparable to that of commercial metal-oxide-semiconductor field-effect transistors and plastic scintillator-based dosimeters. Based on these findings, the developed dosimeter has significant potential for in vivo radiation therapy applications. Full article

Liposomal doxorubicin (Dox), a treatment option for recurrent ovarian cancer, often suffers from suboptimal biodistribution and efficacy, which might be addressed with precision drug delivery systems. Here, we introduce a catheter-based endoscopic probe designed for multispectral, quantitative monitoring of light-triggered drug release. This tool utilizes red-light photosensitive porphyrin−phospholipid (PoP), which is encapsulated in liposome bilayers to enhance targeted drug delivery. By integrating diffuse reflectance and fluorescence spectroscopy, our approach not only corrects for the effects of tissue optical properties but also ensures accurate drug delivery to deep-seated tumors. Preliminary results validate the probe’s effectiveness in controlled settings, highlighting its potential for future clinical adaptation. This study sets the stage for in vivo applications, enabling the exploration of next-generation treatment paradigms for the management of cancer that involve optimizing chemotherapy administration for precision and control. Full article

Transforming growth factor-β₁ (TGF-β₁) promotes the growth and metastasis of lung cancer cells. Therefore, TGF-β₁ siRNA (siTGF-β₁) gene therapy was introduced to inhibit the expression of TGF-β₁ at the nucleic acid level to avert tumor growth and metastasis. However, the delivery of naked siRNA is typically restricted by a short half-life in vivo, difficulties in delivery in vivo, and safety issues. Using siTGF-β₁ as a model drug, we established an actively targeted immunoliposome delivery system to investigate the role of siTGF-β₁ in non-small-cell lung cancer (NSCLC). The results showed that the constructed immune liposomes were in a position to deliver siTGF-β₁ to tumor cells, thus achieving a series of effects such as improving the poor stability and short half-life of naked siRNA. RNA interference of siTGF-β₁ reduced the cell viability, growth, and migration potential of human non-small cell lung cancer cells (A549). Moreover, in an A549 tumor-bearing nude mouse model, siTGF-β₁ transfection markedly reduced tumor growth and tumor volume. Inhibiting TGF-β₁ diminished cancer cell viability and migration and promoted apoptosis in NSCLC, as confirmed by the findings of this study. Therefore, targeting siTGF-β₁ with immunoliposomes may be a new therapeutic strategy for treating non-small-cell lung cancer. Full article

The photosensitizer (PS) in the Photodynamic Therapy (PDT) field represents a key factor, being directly connected to the therapeutic efficacy of the process. Chlorin e6 is a second-generation photosensitizer, approved by the FDA with the most desired clinical properties for PDT applications, presenting high reactive oxygen species (ROS) generation and proven anticancer properties. However, hydrophobicity is a major limitation, leading to poor biodistribution. To overcome this condition, the present work developed an up-to-date nanoemulsion incorporating Ce6 in a new nanosystem (Ce6/NE). A comprehensive study of physicochemical properties, stability, fluorescence characteristics, the in vitro release profile, in vivo and ex vivo biocompatibility, and ex vivo efficacy was established. The nanoemulsions showed the desired particle size and stability over six months, with no spectroscopic or photophysical alterations. Uptake studies demonstrated the internalization of the Ce6/NE in monolayers, with biocompatibility at the lowest concentrations. The HET-CAM assay, however, revealed a higher biocompatibility range, also indicating Ce6/NE’s potential for cancer treatment through antiangiogenic studies. These findings highlight the use of a new promising photosensitizer for PDT modulated with nanotechnology that promotes low toxicity, higher bioavailability, and site-specific delivery. Full article

Transdermal drug delivery minimizes pain and provides a controlled, stable release of drugs, but its effectiveness is limited by the skin’s natural barriers. Microneedles overcome this problem, enabling minimally invasive drug delivery. Microneedle patches (MNPs) with 80 µm-tall needles composed of hyaluronic acid (HA) were developed and evaluated for their formability, structural integrity, dissolution rate, skin penetration ability, and drug transmission capacity. The influence of the molecular weight of HA on these properties was also investigated. MNPs made from low-molecular-weight HA (30 kDa–50 kDa) demonstrated 12.5 times superior drug permeability in ex vivo human skin compared to needleless patches (NLPs). Furthermore, in the same test, low-molecular-weight HA MNPs had 1.7 times higher drug permeability than high-molecular-weight HA MNPs, suggesting superior transdermal administration. The molecular weight of HA significantly influenced its solubility and permeability, highlighting the potential effectiveness of MNPs as drug delivery systems. Puncture tests demonstrated a penetration depth of 50–60 µm, indicating minimal nerve irritation in the dermis and effective drug delivery to the superficial dermal layer. These results present a manufacturing technique for MNPs incorporating model drug compounds and highlight their potential as a novel and minimally invasive drug delivery method for the biomedical applications of soft gels. Full article

Background/Objectives: The present study focused on the formulation and evaluation of novel topical systems containing Salvia officinalis (sage), emphasizing their antioxidant and anti-inflammatory properties. Sage, rich in carnosol, offers considerable therapeutic potential, yet its low water solubility limits its effectiveness in traditional formulations. The aim of our experimental work was to improve the solubility and thus bioavailability of the active ingredient by developing self-nano/microemulsifying drug delivery systems (SN/MEDDSs) with the help of Labrasol and Labrafil M as the nonionic surfactants, Transcutol HP as the co-surfactant, and isopropyl myristate as the oily phase. Methods: The formulations were characterized for droplet size, zeta potential, polydispersity index (PDI), encapsulation efficacy, and stability. The composition exhibiting the most favorable characteristics, with particle sizes falling within the nanoscale range, was incorporated into a cream and a gel, which were compared for their textural properties, carnosol penetration, biocompatibility and efficacy. Results: Release studies conducted using Franz diffusion cells demonstrated that the SNEDDS-based cream achieved up to 80% carnosol release, outperforming gels. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) test and enzyme-linked immunosorbent assays (ELISA) showed strong efficacy, with an in vivo carrageenan-induced rat paw edema model revealing that the SNEDDS-based cream significantly reduced inflammation. Conclusions: These findings highlight the potential of SNEDDS-enhanced topical formulations in improving therapeutic outcomes. Further research is warranted to confirm their long-term safety and efficacy. Full article

Background: In cancer immunotherapy, gene therapy has become a promising strategy through the introduction of immunostimulatory components into its formulation. However, ideal non-viral gene delivery platforms capable of simultaneously maintaining a high delivery efficiency and immune activation are still in demand. As an intestinal probiotic, Lactobacillus reuteri has potential correlation with cancer progression. Its unique antigenicity also confers its immunomodulatory activity. Method: We engineered a new non-viral siRNA delivery system, DMPLAC. By wrapping the lysate of Lactobacillus reuteri, it is expected to enhance the anti-cancer immunostimulatory properties. Result: Supported by certain internalization pathways, the prepared DMPLAC nanoparticles showed high siRNA delivery efficiency in vitro (up to 97.62%). They also strongly promoted the maturation and activation of immune cells, including dendritic and T cells, both in vitro and in vivo. By loading siRNA targeting the immune checkpoint CD47 gene, the DMPLAC/siCD47 complex strongly suppressed the growth of multiple colon cancer models through local administration with high safety. Conclusions: Our study developed a novel intestinal probiotic lysate-based gene delivery system with dual immunomodulatory abilities, suggesting a potential strategy for cancer immunotherapy. Full article

Extracellular vesicles (EVs) are lipid bilayer particles released by virtually all cells, with prominent roles in both physiological and pathological processes. The size, number, and molecular composition of released EVs correlate to the cells of origin, modulated by the cell’s environment and pathologic state. The proteins, DNA, RNA, and protein cargo carried by EVs are protected by degradation, with a prominent role in targeted intercellular signaling. These properties make EVs salient targets as both carriers of biomarkers and potential therapeutic delivery vehicles. The majority of EV research has focused on blood, urine, saliva, and cerebrospinal fluid due to easy accessibility. EVs have also been identified and studied in all ocular biofluids, including the vitreous humor, the aqueous humor, and the tear film, and the study of EVs in ocular disease is a new, promising, and underexplored direction with unique challenges and considerations. This review covers recent advances in the diagnostic and therapeutic use of ocular EVs, with a focus on human applications and key preceding in vitro and in vivo animal studies. We also discuss future directions based on the study of EVs in other organ systems and disease sates. Full article

Hepatitis C virus (HCV) is a major public health concern, and the development of an effective HCV vaccine plays an important role in the effort to prevent new infections. Supramolecular co-assembly and co-presentation of the HCV envelope E1E2 heterodimer complex and core protein presents an attractive vaccine design strategy for achieving effective humoral and cellular immunity. With this objective, the two antigens were non-covalently assembled with an immunostimulant (TLR 7/8 agonist) into virus-mimicking polymer nanocomplexes (VMPNs) using a biodegradable synthetic polyphosphazene delivery vehicle. The resulting assemblies were characterized using dynamic light scattering and asymmetric flow field-flow fractionation methods and directly visualized in their vitrified state by cryogenic electron microscopy. The in vivo superiority of VMPNs over the individual components and an Alum-formulated vaccine manifests in higher neutralizing antibody titers, the promotion of a balanced IgG response, and the induction of a cellular immunity—CD4+ T cell responses to core proteins. The aqueous-based spontaneous co-assembly of antigens and immunopotentiating molecules enabled by a synthetic biodegradable carrier offers a simple and effective pathway to the development of polymer-based supramolecular nanovaccine systems. Full article

Background: Amphotericin B (AmB) is a commonly utilized antifungal agent, which is also recommended for the treatment of certain neglected tropical diseases, including leishmaniasis. However, its clinical application is constrained because of its poor oral bioavailability and adverse effects, prompting the investigation of alternative drug delivery systems. Polymeric nanoparticles (PNPs) have gained attention as a potential drug delivery vehicle, providing advantages such as sustained release and enhanced bioavailability, and could have potential as AmB carriers. However, concerns persist regarding nanomaterials’ toxicity, requiring more studies. Zebrafish (Danio rerio) embryos were used as a valuable model for toxicity testing, especially because of their genetic similarity to humans and standardized developmental assessments. Methods: In this study, we produced and characterized AmB loaded and non-loaded PNPs by nanoprecipitation, dynamic light scattering, transmission electron microscopy, atomic force microscopy and spectroscopy. Afterwards, we verified their toxicity through in vitro MTT assays in three cell lines (HEK293, HepG2, and J774 A1) and in vivo tests with zebrafish embryos. Results: In both trials, it was noted that nanoencapsulation of the drug led to increased toxicity when compared to non-encapsulated AmB, possibly indicating that they penetrated the embryo’s chorion. Nevertheless, it was demonstrated that the polymers used are safe and they are not the cause of toxicity, neither are the nanostructures per se. Conclusions: Therefore, it is believed that the objective of improving the bioavailability of AmB may have been achieved, and the observed toxicity was probably linked to AmB’s ability to destabilize cell membranes. Full article

In recent years, the near-infrared (NIR) fluorescence theranostic system has garnered increasing attention for its advantages in the simultaneous diagnosis- and imaging-guided delivery of therapeutic drugs. However, challenges such as strong background fluorescence signals and rapid metabolism have hindered the achievement of sufficient contrast between tumors and surrounding tissues, limiting the system’s applicability. This study aims to integrate the pegylation strategy with a tumor microenvironment-responsive approach. A novel esterase-activated EPR strategy prodrug, OBHSA-PEG-DCM, was designed. This prodrug links OBHSA, a protein degrader capable of efficient ERα protein degradation, to the PEG-modified fluorescent group (dicyanomethylene-4H-pyran, DCM) via an ester bond. This integration facilitates targeted drug delivery and enhances the retention of the fluorescent group within the tumor, allowing distinct in vivo tumor imaging periods. Experimental results show that, benefiting from overexpressed esterase in cancer cells, OBHSA-PEG-DCM can be efficiently hydrolyzed, releasing OBHSA and pegylated DCM. OBHSA demonstrated potent inhibition against MCF-7 cells (IC₅₀ = 1.09 μM). Simultaneously, pegylated DCM exhibited remarkable in vivo imaging capabilities, lasting up to 12 days in mice, due to the enhanced permeability and retention (EPR) effect. OBHSA-PEG-DCM holds promise as a theranostic agent for ERα-positive breast cancer, offering both therapeutic and diagnostic capabilities. Importantly, this study highlights the utility of pegylated NIR fluorophores for long-circulating drug delivery systems, addressing current challenges in achieving high-contrast tumor imaging and effective targeted drug release. Full article

Objectives: This in vivo study introduces a newly developed spirooxindole derivative that is deemed safe and effective as a potential targeted therapy for various cancers. Methods: Extensive in vivo investigations, including histopathology, immunohistochemistry, and molecular biology, validated its potential for further preclinical and clinical exploration, necessitating comprehensive examinations of its bioavailability, pharmacodynamics, and pharmacokinetics. Additionally, this study involves the development of a commercially viable proniosomal drug delivery system for the compound, facilitating controlled drug release. Results: The data revealed efficacy of spirooxindole derivative in halting the progression of liver cancer, metastasis, and portal vein thrombosis, with potential implications for enhancing regeneration and recovery of early-stage cancer cells in multiple organs, thereby improving recovery rates and remission among cancer patients. The proniosomes, loaded with the compound, exhibited high entrapment efficiency and prolonged drug release rates of up to 12 h in vitro. The optimized formula demonstrated superior drug release percentages and stability compared to conventional niosomes. Further analysis via FTIR and DSC confirmed the absence of chemical interactions and proper entrapment of the compound within the nanovesicles, indicating a stable and effective drug delivery system. Conclusions: This study presents a novel, safe, and effective chemical entity of spirooxindole derivatives for further preclinical and clinical studies. Full article

Background/Objectives: Platycodon grandiflorus (PG) has been widely researched as a conductant drug for the treatment of lung diseases by ancient and modern traditional Chinese medicine (TCM) practitioners. Inspired by the mechanism and our previous finding about fructans and fructooligosaccharides from Platycodon grandiflorus (FFPG), we developed a nano drug delivery system (NDDS) targeting lung cancer. The aim was to improve the efficiency of the liposomal delivery of Paclitaxel (PTX) and enhance the anti-tumor efficacy. Methods: The FFPG-Lip-PTX NDDS was prepared by electrostatic adsorption. Dynamic light scattering, zeta potential, and transmission electron microscopy were used for physical characterization. The release behavior of the NDDS was simulated by dialysis. The uptake of the NDDS was observed by confocal microscopy and flow cytometry. Cytotoxicity, apoptosis, migration, and invasion experiments were used to evaluate the anti-tumor ability of the NDDS in vitro. The penetration and inhibition of tumor proliferation were further analyzed via a 3D tumor sphere model. Finally, in vivo biological distribution and pharmacodynamic experiments verified the targeting and anti-tumor ability of the FFPG-Lip-PTX NDDS. Results: FFPG-Lip-PTX possessed a homogeneous particle size distribution, high encapsulation efficiency, and stability. In vitro experiments confirmed that FFPG promoted the uptake of the NNDS by tumor cells and enhanced cytotoxicity. It also increased the anti-tumor effect by promoting cell apoptosis and inhibiting invasion and metastasis. The same conclusion was obtained in 3D tumor spheres. In vivo experiments exhibited that FFPG-lips-PTX showed more significant lung cancer-targeting activity and anti-tumor effects. Conclusions: In this study, a novel lung-targeted NDDS is proposed to enhance the therapeutic effect of chemotherapy drugs on lung cancer. Full article