Frontiers in drug delivery最新文献

Ovarian cancer treatment by chemotherapy is often complicated by severe systemic toxicity, highlighting the need for targeted delivery techniques that can improve drug efficacy while minimizing off-target effects. Our previous research identified the G protein-coupled receptor (GPCR), coagulation factor II thrombin receptor/protease activated receptor 1 (F2R/PAR1), as a potential therapeutic target in metastatic ovarian cancer tissues. Here we report the design of an engineered lipid nanoparticle (LNP), conjugated with a synthetic short peptide agonist that mimics the F2R-activating tethered ligand. Doxorubicin (DOX)-loaded LNPs (LNP-DOX), were physically characterized to assess the drug encapsulation efficacy, particle size, polydispersity index (PDI), zeta potential, and release kinetics. In vitro investigation demonstrated that the peptide-conjugated LNPs had significantly increased cellular uptake and cytotoxicity compared to their non-conjugated equivalents in an established ovarian cancer cell line. The results underscore the therapeutic potential of ligand-directed nanocarriers for targeted drug delivery into ovarian cancer cells and further validates F2R as a promising cell surface target.

Metastatic breast cancer is associated with very poor overall survival and a reduced quality of life. HER2-positive breast cancer forms brain metastases at the late stages. Established therapies such as trastuzumab, pertuzumab, trastuzumab/pertuzumab, lapatinib and tucatinib are widely used and are selectively toxic to HER2-positive breast cancer cell line. However, the effects of these therapies on the properties of the blood-brain barrier (BBB) remain unclear. We investigated this using an in vitro human BBB model derived from CD34⁺ cells differentiated into brain-like endothelial cells (BLECs) and hCMEC/D3 cell line. BLECs were treated with different concentrations of trastuzumab, pertuzumab, trastuzumab/pertuzumab, lapatinib or tucatinib for 24 h and 48 h. We measured cell viability, transendothelial electrical resistance (TEER), paracellular permeability to fluorescein and mRNA expression profiles. Most treatments showed no effect on cell viability, permeability and TEER of endothelial cells. While treatment of BLECs with lapatinib and tucatinib at low concentrations resulted in increased cell viability/metabolism, treatment with a higher concentration of 5 μg/mL resulted in toxic effects. These results were confirmed using another BBB in vitro model, hCMEC/D3. Treatment with trastuzumab and trastuzumab/pertuzumab resulted in changes in the mRNA expression of BBB marker genes encoding efflux pumps (P-gp (ABCB1)/BCRP (ABCG2)), the glucose transporter GLUT-1 (SLC2A1), tight junction proteins (occludin (OCLN)/claudin-5 (CLDN5)) and the pro-inflammatory chemokine CCL2. In conclusion, we demonstrate different time- and concentration-dependent effects of anti-HER2-targeted therapies for the treatment of advanced HER2-positive breast cancer on the BBB in vitro. Further experiments are required to assess the clinical relevance of our results.

Glucocorticoids are cornerstone treatment for inflammatory diseases but are limited by systemic toxicity from high-dose and prolonged use. Encapsulation of dexamethasone sodium phosphate (DSP) in autologous erythrocytes aims for sustained drug release with an improved safety profile. This manuscript summarizes early clinical studies of encapsulated DSP (eDSP) in pulmonary and inflammatory bowel disorders (IBD). From 2001 to 2013, eight clinical studies investigated eDSP in patients whose age ranged from 5 to 83 years, with chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), Crohn's disease (CD), and ulcerative colitis (UC). DSP was loaded into autologous erythrocytes ex vivo and reinfused every 2 weeks, or monthly. Follow-up ranged from 1 to 24 months. In pulmonary indications, eDSP resulted in improved FEV1 and reduced infections in CF patients, and improved symptoms in COPD with markedly reduced corticosteroid doses. In IBD, eDSP enabled steroid withdrawal in 60%-78% of patients and achieved remission in pediatric and adult CD and UC. Adverse effects typical of corticosteroids were notably absent. Limitations of these studies included small sample sizes, lack of placebo groups in some trials, and inter-patient variability in erythrocyte drug loading. Pharmacokinetic studies documented persistence of dexamethasone levels up to 4 weeks post-infusion. Early studies demonstrate that eDSP is a feasible and well-tolerated treatment in children and older patients, delivering low-dose corticosteroids with prolonged therapeutic levels. These findings support further development of erythrocyte-based drug delivery for chronic inflammatory diseases in patients with steroid sensitive or steroid-dependent disease.

The blood-brain barrier (BBB) restricts development of drug delivery systems for brain, which hinders the potential applications of numerous pharmaceutical agents for treating central nervous system (CNS) diseases. A number of drug delivery systems have been developed to enhance the capacity of drugs to cross BBB. A detailed introduction of the structure and function of BBB was given based on the mechanism of BBB, while comparing with the pathological changes of BBB in neurodegenerative diseases (NDDs), including activation of endothelial cells, the loose of tight junction and increase of BBB permeability. The liposomes, polymer nanoparticles and other novelty approaches for treating NDDs were summarized. Here, we provide a novel perspective to classify the strategies of drug delivery system as passive targeting and active targeting according to their mechanisms. The potential of clinical translational for drug delivery systems in NDDs was explored and underscored the imperative of safety and verification through clinical trials. In summary, this review proposed current developments of drug delivery systems and discussing the potentials of drug delivery systems in clinical translational which bring new breakthroughs for treating NDDs.

Colorectal cancer is among the most redundant cancer of the gastrointestinal tract, with its burden expected to rise 60% by 2030. Morin hydrate (MH) is a bioflavonoid with anticancer attributes. However, the implementation of MH is limited due to its hydrophobic properties, along with poor stability and bioavailability. Protein-based nanoparticle may encapsulate the drug and this complex can enhance the drug efficacy and delivery to colorectal carcinoma cells. To investigate the molecular interactions between BSA and MH, the Lamarckian genetic approach was used. In the current study, we prepared BSA encapsulated MH nanoparticles by desolvation method. The characterization of the nanoparticles was done by XRD, DSC, TGA and FTIR was performed to corroborate the results. MHNPs were spherical with a particle size of 90 nm determined by TEM and a zeta potential of -11 ± 5.90 mV. BSA nanoparticles improve the thermal stability and sustained release profile of Morin Hydrate, enabling its application as a phytochemical-based anticancer nanocarrier. The antioxidant test of MHNPs showed higher radical scavenging ability than MH. Additionally, our release investigations show that drug release occurs from the matrix of the nanoformulation to reach the target site efficiently. An increase in the anticancer potential was shown by an in vitro cytotoxicity assay in comparison to MH. These data suggest that MH was successfully encapsulated and enhanced solubility, resulting in greater bioavailability.

Traditional cancer treatment methods often encounter limitations, such as poor targeting, low bioavailability, and high systemic toxicity. These challenges have led researchers to explore alternative therapeutic strategies. Nickel nanoparticles (NiNPs), owing to their distinctive physicochemical properties and tunable biocompatibility, have attracted considerable attention in cancer therapy and drug delivery applications. These nanomaterials demonstrate excellent magnetic properties, photothermal conversion capabilities, catalytic activity, and potential for multifunctionality and targeted drug delivery via surface modification. This review highlights recent advancements in the use of NiNPs for cancer treatment, emphasizing their advantages as drug carriers that enhance the bioavailability, targeting, and therapeutic efficacy of anticancer agents. Additionally, the synergistic applications of NiNPs in multimodal therapies, including magnetic hyperthermia, photothermal therapy, and chemodynamic therapy, are discussed, as well as their potential as theranostic platforms. Although nickel-based nanodelivery systems show significant promise for clinical translation, issues related to biosafety, degradation metabolism, and long-term toxicity remain and require further investigation to support their clinical application.

Gene therapy, a pivotal cornerstone in biomedical research, has emerged as a transformative approach for addressing a wide spectrum of dermatologic conditions, including hereditary disorders, chronic wounds, and immune related skin diseases. The skin, with its expansive surface area and regenerative capacity, serves as an ideal platform for localized gene delivery. However, conventional gene therapy strategies face critical limitations, such as high costs, suboptimal transfection efficiency, immunogenicity, and off-target effects. In this context, gene hydrogels have emerged as an innovative paradigm, offering tailored physicochemical and biological functionalities to overcome these challenges. Gene hydrogels are distinguished by their tunable morphologies (e.g., particulate or bulk gel configurations), which enable precise control over therapeutic release kinetics and spatial distribution. Their three-dimensional polymeric networks recapitulate the extracellular matrix, functioning as bioactive scaffolds that enhance tissue regeneration, facilitate cell migration, and accelerate wound healing. By integrating stimuli-responsive polymers, these hydrogels achieve spatiotemporal control of gene delivery, improving target specificity while minimizing systemic exposure. Furthermore, their inherent biocompatibility and biodegradability mitigate immunogenic risks and prevent long-term residue accumulation, addressing pivotal safety concerns in clinical translation. This review systematically examines the multifaceted advantages of gene hydrogels, including their ability to bypass the stratum corneum barrier, protect genetic payloads from enzymatic degradation, and sustain localized therapeutic effects over extended periods. Recent advancements in "smart" hydrogels, responsive to pathological cues such as pH fluctuations or matrix metalloproteinase overexpression, further underscore their potential in personalized medicine. By synergizing material science with gene-editing technologies, gene hydrogels represent a revolutionary leap toward precision dermatologic therapies. Future challenges, such as scalable manufacturing and dynamic regulatory mechanisms, are critically analyzed alongside opportunities in intelligent material design and interdisciplinary innovation. This comprehensive analysis positions gene hydrogels as a cornerstone for next-generation dermatologic therapeutics, bridging the gap between laboratory innovation and clinical impact.