Journal of Drug Targeting最新文献

Atopic dermatitis (AD) is the most widespread chronic inflammatory skin disease characterised by impaired skin barrier, higher immunoglobulin E (IgE)-mediated sensitisation, and pronounced inflammatory and immune activity. In this study, mizolastine-loaded spanlastics (MZSPs) with edge activators (Brij 35, Tween 80, and Cremophor RH40) were formulated using ethanol injection method. Spanlastics were assessed for their average particle size, surface charge, encapsulation efficacy, morphology, in vitro drug release, and ex vivo skin permeation. MZSPs showed average particle size ranging from 186.2 ± 13.0 nm to 380.7 ± 25.9 nm and high MZ encapsulation efficiency percentage of (95.8 ± 0.68%-98.1 ± 0.86%). The prepared MZSPs were incorporated into 2.5% HPMC hydrogel base to facilitate its topical delivery. The in vitro release experiments showed a sustained release profile of MZ from MZSPs-hydrogel over 24 h with effective flux and permeation through rat skin compared to free drug. Additionally, the therapeutic efficacy of MZSPs-hydrogel in an AD model utilising seven-week-old male Balb/C mice outperformed the free drug in improving cytokine profiles, histopathological and immunohistochemical parameters, along with a quantitative analysis of mast cell immunostaining. These findings support the potential application of MZSPs for the transdermal delivery of MZ, offering enhanced management for AD.

Liposomes composed of phospholipids (PLs) either alone or with an active molecule, can reveal a significant potential in the improvement of severe disorders such as Alzheimer's disease, osteoporosis, and inflammatory conditions. For instance, PLs exhibit anti-inflammatory, antioxidant, neuroprotective, and osteogenic properties in pathological conditions which accelerate the therapeutic effect of the drugs. These pharmacological properties can be modulated by the type and dose of PLs or liposome administration. They affect disorders through the signalling pathways, down or upregulation of gene expression, balance of oxidative stress, and other biological mechanisms. Interestingly, liposomes containing essential PLs like phosphatidylserine with active molecules such as curcumin or alendronate could synergistically improve certain diseases like osteoporosis in experimental models. Accordingly, we aimed to highlight the unique advantages of various PLs or liposomes with an emphasis on their diverse therapeutic modalities and potentiation of liposomes in synergy with the cargos in experimental studies. These properties suggest a promising approach to enhance drug efficacy and mitigate the side effects through reduced drug usage in chronic diseases, however, their clinical translation requires further validation of safety and effectiveness in human.

Type 1 diabetes (T1D) is an autoimmune disease characterised by the destruction of insulin-producing β cells, which leads to chronic hyperglycaemia and lifelong insulin dependence. Despite advances in diabetes care, achieving optimal glucose control and preventing complications remains a challenge. Gene therapy has emerged as a transformative approach, targeting the underlying mechanisms of β-cell destruction and immune dysregulation. Studies have suggested the feasibility of using viral vectors, such as adeno-associated viruses (AAVs) and lentiviruses, to deliver genes aimed at preserving pancreatic function and restoring immune balance. Innovative strategies, including CRISPR/Cas9-based genome editing and non-viral delivery systems, offer promise for addressing safety and efficacy challenges. This systematic review aims to evaluate the current state of gene therapy in T1D, focusing on findings from preclinical studies and ongoing clinical trials. It explores key approaches, such as β-cell regeneration, immune tolerance induction, and metabolic regulation, while critically assessing challenges related to delivery efficiency, long-term effects, and scalability. By synthesising existing evidence, this review provides a comprehensive overview of the progress and obstacles in translating gene therapy into a viable treatment for T1D, highlighting future directions to accelerate clinical application.

The stroma plays a pivotal role in the development of prostate tumours. The tumour stroma includes different immune and stromal cells. Stromal cells can include fibroblasts, activated fibroblasts, endothelial cells, stem cells, etc. Immune system cells also consist of different subsets of T cells, B cells, macrophages and myeloid cells. Targeting different cells and their expressed or released molecules and genes in the tumour stroma has been proposed as an intriguing strategy for remodelling stroma and repressing prostate cancer (PCa) growth. Leveraging nanotechnology, researchers have developed innovative strategies to target these components. This review examines the latest progress in nanoparticle-based therapies specifically designed to interact with the prostate tumour stroma. We overview the functionalisation and targeting mechanisms of various nanoparticles, including organic and inorganic nanoparticles, highlighting their ability to specifically target stromal elements such as fibroblasts, extracellular matrix (ECM) and immune cells in PCa. Furthermore, we evaluate the synergistic potential of combining nanoparticle-based targeting with other therapies such as chemotherapy, radiotherapy, targeted therapy and photothermal and photodynamic therapies.

In this study, we developed a novel theranostic nanoplatform integrating a covalent organic framework (COF) with superparamagnetic iron oxide nanoparticles (SPIONs) for targeted cancer therapy and diagnosis. The system was engineered to co-deliver deferasirox (DFX), an iron chelator, and a MUC1-specific aptamer for selective targeting of cancer cells. This multifunctional architecture enables simultaneous imaging via MRI and enhanced therapeutic efficacy through targeted drug delivery. Both in vitro and in vivo experiments demonstrated promising antitumor performance and selective cytotoxicity towards cancer cells compared to non-targeted controls. These findings highlight the potential of COF-based platforms in advancing personalised nanomedicine.

Sutures play an essential role in surgical operations, as they secure and stabilise the edges of wounds to facilitate healing. Nonetheless, microbes on sutures can heighten the likelihood of surgical site infections (SSI) because of pathogen colonisation. This research focused on addressing surgical site infections (SSI) by creating silver nanoparticles (Ag-NPs) through a modified nanoprecipitation technique and utilising them to coat antimicrobial sutures. The physiochemical characteristics of Ag-NPs were confirmed by morphology (through TEM) with a particle size of 26.23 ± 0.234 nm, a PDI of 0.383 ± 0.156, and a zeta potential range of 1.04 ± 0.0.98 mV. Drug content and release studies were conducted for Ag-NP-coated silk sutures. Scanning electron microscopy (SEM) was conducted to determine the coating of Ag-NP-coated silk sutures. Antimicrobial activity was studied using five microorganisms (E. coli, P. aeruginosa, E. faecalis, S. aureus, and T. asperellum) for Ag-NP-coated silk sutures. The cytotoxicity of the Ag-NP-coated silk sutures was investigated using HaCaT for 24 h, which exhibited good cell viability. Finally, this study evaluates the pharmacokinetics of Ag-NP-coated silk sutures in a rat model to determine the pharmacokinetic profile of Ag. Overall, the results indicate that Ag-NP-coated sutures can potentially be used as antimicrobials to diminish or inhibit SSI in postoperative or general surgery patients.

Lung cancer is a leading cause of cancer-related mortality, with approximately 2 million new cases and 1.8 million deaths annually, and studies suggest that by 2050, these numbers will reach 3.8 million cases and 3.2 million deaths. The high mortality rate highlights the urgent need for early diagnosis and rapid drug development. Genomic approaches provide insights into tumour biology, supporting personalised medicine. This study explores the role of machine learning (ML) in enhancing genomic analysis and drug discovery for lung cancer treatment. A comprehensive PubMed search was conducted to identify relevant publications from the last 10 years. Selected studies were critically reviewed to understand how ML algorithms are applied in lung cancer genomics and drug discovery. ML algorithms such as random forests, gradient boosting, support vector machines, autoencoders, CNNs, and RNNs are widely used for genomic pattern identification. Techniques like reinforcement learning, deep neural networks, GANs, and GNNs are employed for drug discovery. ML models have achieved over 95% accuracy in certain lung cancer applications. However, challenges remain, including data scarcity and model interpretability. ML significantly enhances lung cancer's genomic analysis and drug design; however, further optimisation and clinical validation are essential for effective real-world implementation.

Human epidermal growth factor 2-negative breast cancer (HER2-BC) is characterised by the lack of HER2 amplification and encompasses triple-negative breast cancer and hormone receptor-positive HER2-negative breast cancer. Triple-negative breast cancer is distinguished by a total lack of oestrogen and progesterone receptors, along with the lack of HER2 amplification. While hormone receptor-positive HER2-negative breast cancer is marked by expression of oestrogen receptors with or without progesterone receptors. The major drawback of triple-negative breast cancer is the lack of an enforceable biomarker, and that of hormone receptor-positive HER2-negative breast cancer is endocrine therapy resistance. Consequently, these therapeutic failures result in relapse/recurrence, disease progression, and ultimately a poor prognosis. Sacituzumab govitecan is a novel 3^rd generation antibody-drug conjugate that selectively blocks trophoblast cell-surface antigen-2, a highly expressed protein in HER2-BC. This review elaborates on the shortcomings of the standard therapeutic regimens in HER2-BC and the role of Sacituzumab govitecan in addressing these limitations. Clinical trials proposing its application in locally advanced HER2-BC have also been included. Furthermore, clinical trials showcasing the combination of Sacituzumab govitecan with numerous therapeutic modalities improving patient survival and quality of life in metastatic disease have also been included in the text.

The emergence of novel long-acting and antiretroviral (ARV) drug delivery systems has reshaped the landscape of HIV pre-exposure prophylaxis (PrEP). Intravaginal delivery platforms are increasingly recognised for their ability to deliver ARVs directly at the portal of viral entry. These systems are well retained at the portal, ensuring sustained local inhibitory levels, minimising systemic exposure. Compared to oral PrEP, these systems offer better protection against viral transmission, reduce dosing frequency and minimise systemic side effects. Among these systems, polymeric nanoparticles (NPs) stand out due to their customisable surface chemistry, mucoadhesive potential and sustained drug release profiles, ensuring enhanced mucosal retention and minimal systemic absorption. Recent innovations integrate these NPs into versatile platforms such as in situ gelling systems, bioadhesive films, microneedles, vaginal rings and electrospun nanofibres. These specialised platforms have demonstrated superior user acceptance, stability and pharmacokinetics compared to traditional vaginal formulations. Cell-based HIV challenge models using engineered TZM-bl and PHA-stimulated peripheral blood mononuclear cells (PBMCs) have emerged as reliable in silico tools for evaluation of viral inhibition, cytotoxicity and mucosal interaction of NPs. This review critically highlights recent advances in intravaginal polymeric NP-based carrier systems for effective and sustained HIV prevention.

Glioblastoma multiforme (GBM) treatment is hindered by the blood-brain barrier (BBB) and an immunosuppressive tumour microenvironment (TME) rich in M2 tumor-associated macrophages (TAMs). Carmustine (BCNU) efficacy is limited by systemic toxicity. To address this, we developed transferrin-modified, BCNU-loaded superparamagnetic iron oxide nanoparticles (Tf/BCNU-SPIONs) for nose-to-brain delivery. Optimized Tf/BCNU-SPIONs were monodisperse (41.92 ± 2.81 nm), with high BCNU encapsulation (>80%) and transferrin anchoring (∼98%). Cellular studies showed Tf/BCNU-SPIONs enhanced Gl261 cellular uptake 2.1-fold versus non-targeted nanoparticles, achieving 76.4 ± 6.29% apoptosis at 8 h. In orthotopic GBM mice, single-dose intranasal administration suppressed tumour growth by 84.6 ± 5.3% (p < 0.01 vs. saline) and extended maximum survival to >60 days (vs. 48 days for free BCNU), due to BBB bypass and transferrin targeting. Crucially, SPIONs reprogrammed TAMs in the TME, increasing M1 polarization to 41.8 ± 6.5% (vs. 6.5 ± 3.2% in controls, p < 0.01). Safety assessments showed minimal hepatorenal/hematologic toxicity (p > 0.05 vs. saline) at just 20% of the clinical BCNU dose. This work establishes a synergistic chemo-immunotherapeutic strategy that concurrently overcomes BBB limitations, reprograms the immunosuppressive TME, and mitigates systemic toxicity, demonstrating promising preclinical efficacy.