Journal of Drug Targeting最新文献

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.

Oral cancers frequently metastasise to adjacent cervical lymph nodes (CLNs), leading to systemic dissemination and poor prognosis. Intranasal (i.n.) drug delivery provides direct access to cervical lymphatics, enabling high local drug concentrations while minimising systemic exposure. This study evaluated the pharmacokinetics (PK) and anti-metastatic efficacy of two vascular endothelial growth factor receptor (VEGFR)-3 inhibitors - cediranib maleate (CDNB) and pazopanib hydrochloride (PPNB) - administered i.n. in a mouse model of tongue cancer. Pharmacokinetic analysis showed that i.n. delivery yielded significantly higher CLN concentrations of both drugs than intravenous administration, despite lower plasma levels. In tumour-bearing mice, i.n. CDNB markedly reduced the incidence of CLN metastasis (0.167) versus controls (0.875, p < .01) and was more effective than intraperitoneal CDNB (0.571) or i.n. PPNB (0.500). Although less potent, PPNB significantly reduced the number of metastatic CLNs (0.438, p < .05). CDNB exhibited superior and more consistent efficacy. The reduced effect of PPNB may reflect its lower dose - limited by solubility - and possible differences in target specificity. These findings highlight the potential of i.n. administration to deliver VEGFR-3 inhibitors to CLNs, suppress lymphangiogenesis and lymphatic metastasis, and reduce systemic toxicity. This approach may offer a non-invasive alternative to neck dissection in oral cancer.

This work aims to assess mechanisms of synthesis of folate-conjugated mesoporous silica nanoparticles (MNPs) for targeted delivery of paclitaxel in cancer treatment. Paaclitaxel, while potent, suffers from poor solubility and severe side effects due to off-target toxicity. The important factors including particle size (140 ± 6 nm), zeta potential (-29.2 ± 1.5 mV), drug loading (11.3 ± 0.8%), and entrapment efficiency (89.5 ± 1.7%) were determined by response surface methodology (RSM) by employing polynomial equations derived from factorial design. In biological fluids, optimised MNPs had good stability, low degree of aggregation (≤5%) and low drug release (≤4%). In vitro cytotoxicity analysis established higher anti-cancer efficacy, the optimised formulation depicted 78.5% tumour cell mortality to contrast with the 58% with free paclitaxel. In vivo, the MNPs containing paclitaxel enhanced the tumour targeting effect with the 87% of tumours observed with the treatment, while Taxol^® was effective in only 65% of the cases, and free paclitaxel in 58%. These results highlight the promise of folate-decorated MNPs as an advanced nanocarrier for safer and more effective paclitaxel chemotherapy, with significantly reduced systemic toxicity compared to commercial Taxol^®. However, further studies assessing drug penetration in larger tumour volumes and addressing scalability for clinical are warranted.

Background: Glycemic memory contributes to the progression of diabetic nephropathy (DN) despite glycemic control. This study investigates γ-aminobutyric acid (GABA), a natural compound with 82.5% structural similarity to metformin, for its potential in mitigating glycemic memory and DN.

Methods: Structural similarity and molecular docking identified GABA as a SIRT1-targeting metformin analog (binding affinity: 5.8 kcal/mol), supported by ADME profiling. In vitro assays assessed antioxidant activity (DPPH IC₅₀: 141.09 µg/mL), cytotoxicity (MTT assay), oxidative stress markers, and histone H3 acetylation. In vivo, high-fat diet-fed Sprague-Dawley rats underwent dietary reversal and GABA treatment (100/200 mg/kg) to evaluate metabolic, renal, hepatic, oxidative, and epigenetic effects.

Results: GABA maintained >90% cell viability at 5 µM, with no cytotoxicity up to 150 µM. It reduced oxidative markers and restored histone acetylation in vitro. In vivo, 200 mg/kg GABA treatment significantly reduced cholesterol (44.44%), triglycerides (28.64%), and LDL (40.80%), while increasing HDL by 103.65%. At 100 mg/kg, GABA lowered blood urea (30.43%), creatinine (4.65%), uric acid (75.00%), bilirubin (53.57%), SGOT (54.24%), SGPT (39.52%), and ALP (60.58%), with histopathological improvements in renal tissues.

Conclusion: GABA exhibits antioxidant, hepatoprotective, and renoprotective properties, highlighting its potential as a therapeutic agent for glycemic memory-associated DN.

Skin cancer is the most prevalent malignancy, with rising incidence and morbidity, particularly among the white population. This study aims to develop a dual drug-loaded nanoemulsion (NE) gel incorporating 5-fluorouracil (5-FU) and lepidine (LPD) to enhance drug deposition in the stratum corneum and dermal layer for improved skin cancer therapy. Oil-in-water (o/w) NEs were prepared using peppermint oil, Tween 80 and PEG-400 via aqueous phase titration method and optimised through pseudo-ternary phase diagrams. The optimised dual drug-loaded NE showed particle size of 131.7 ± 3.21 nm, PDI of 0.21 ± 0.005 and zeta potential of -26.24 ± 1.532 mV. This NE was then dispersed into a 1% carbopol 934 gel for topical application. In vitro and ex vivo studies demonstrated significantly enhanced drug deposition and prolonged release (**p < .001) compared to a conventional gel. Furthermore, dermatokinetic and CLSM studies confirmed enhanced skin permeation and deeper drug distribution. Skin irritation studies indicated that the NE gel was safe and non-irritant. It is concluded that the developed 5-FU and LPD co-loaded NE gel enhances topical drug delivery against skin cancer by improving drug absorption and distribution between the epidermis and dermis in rodent skin model, which could represent promising strategy for the management of skin cancer.

This review critically evaluates the emerging role of lactoferrin, an iron-chelating glycoprotein, as a macromolecular ligand in precision cancer therapy. Lactoferrin exhibits potent anti-tumour, anti-inflammatory, and immunomodulatory properties and targets cancer cells via high-affinity binding to transferrin and LDL receptor-related proteins, enhancing selectivity and minimizing off-target toxicity. It modulates key oncogenic pathways such as PI3K/Akt and MAPK to suppress tumour growth and metastasis. Nanoformulations-like liposomes and polymeric nanoparticles-improve pharmacokinetics, enable targeted drug delivery, and enhance therapeutic efficacy. Lactoferrin's ability to cross biological barriers, including the blood-brain barrier via receptor-mediated transcytosis, offers promise for treating difficult cancers such as glioblastoma. Additionally, it enhances anti-tumour immunity by activating NK cells and polarizing macrophages to the M1 phenotype. Importantly, lactoferrin helps overcome multidrug resistance by modulating efflux pumps like P-glycoprotein. Integrating molecular insights with preclinical and clinical evidence, this review underscores lactoferrin's transformative potential in precision oncology through advanced nanoformulations and synergistic immunomodulatory mechanisms.