Journal of Drug Targeting最新文献

Ferulic acid (FA) is a phenolic compound obtained naturally and is a versatile antioxidant identified for its potential in managing hypertension. However, its application is constrained due to its classification as a BCS Class IV moiety. To address this, we concentrated on improving its solubility and permeability by developing nanostructured lipid carriers (NLCs) of FA using emulsification probe sonication technique. Lipids stearic acid and Labrasol, surfactant Tween 80, and sonication time were adopted for the formulation studies, with optimization utilizing Box-Behnken design. The FA-NLCs were evaluated for particle size, zeta potential, PDI, entrapment efficiency, and in vitro release. Pharmacokinetic and intestinal uptake studies were carried out on male Wistar rats. Pharmacodynamic studies were performed using the high fructose diet model for hypertension in Sprague Dawley rats.In-silico studies, exposed a strong interaction between FA and ACE receptor (1UZF), with docking score of -7.144 kcal/mol and binding energy of -54.624 kcal/mol. Optimized formulation (F12 FA-NLC) established a particle size of 103.4 ± 8.89 nm, zeta potential of -43.6 mV, polydispersity index of 0.531 ± 0.021, and entrapment efficiency of 88.90 ± 6.27%. In-vitro release studies displayed, that plain FA released 103.13 ± 8.80% within 4 hours, whereas, FA-NLCs released 40.34 ± 5.35% drug after 24 hours indicating sustained release.Pharmacokinetic studies of FA-NLC showed a 2.6-fold increase in C _max and a 1.9-fold increase in AUC and half-life compared to pure FA, which was extremely significant (p < 0.001). Pharmacodynamic assessments specified that FA-NLC significantly reduced blood pressure by 39.9 ± 7.10 mmHg over 8 hours, compared to 30.8 ± 8.12 mmHg for plain FA (p < 0.001). Intestinal uptake results emphasized significant lymphatic uptake via clathrin-mediated endocytosis, bypassing first-pass metabolism, thus, improving therapeutic efficacy. Therefore, the study concluded that FA-NLC effectively reduced blood pressure as compared to plain FA.

Mutations that overexpress the epidermal growth factor receptor (EGFR) are linked to cancers like breast (15-20%), head and neck (10-15%), colorectal (5-8%), and non-small cell lung cancer (10-50%), especially in East Asian populations. EGFR activation stimulates 'RAS/RAF/MEK/ERK, PI3K/Akt, and MAPK' pathways, which enhance cell division, survival, angiogenesis, and tumour growth while inhibiting apoptosis and metastasis. Secondary mutations (e.g. 'T790M', 'C797S'), off-target effects, and resistance due to alternate pathway activation reduce the efficacy of currently available EGFR inhibitors. To address these issues, 'novel heterocyclic inhibitors with structural versatility were developed to improve selectivity and binding affinity for mutant EGFR forms'. These new EGFR reduce side effects, enhance pharmacokinetics, and enhance therapeutic efficacy at low concentrations. This review focuses on 'EGFR mutations in various cancers' detailing the biochemical effects, clinical profiles, and binding interactions of globally approved EGFR inhibitors. Furthermore, it focuses into recent progress in nano-formulations and the development of heterocyclic derivatives that can successfully 'target mutant EGFRs' through varied synthesis methods. These inhibitors have the potential to have better binding affinities, selectivity's, and less side-effect. Further research required to refine the structures and develop nanoformulations of EGFR-targeted therapeutics in order to improve therapeutic efficiency and, provide more effective cancer treatments.

A significant area of computer science called artificial intelligence (AI) is successfully applied to the analysis of intricate biological data and the extraction of substantial associations from datasets for a variety of biomedical uses. AI has attracted significant interest in biomedical research due to its features: (i) better patient care through early diagnosis and detection; (ii) enhanced workflow; (iii) lowering medical errors; (v) lowering medical costs; (vi) reducing morbidity and mortality; (vii) enhancing performance; (viii) enhancing precision; and (ix) time efficiency. Quantitative metrics are crucial for evaluating AI implementations, providing insights, enabling informed decisions, and measuring the impact of AI-driven initiatives, thereby enhancing transparency, accountability, and overall impact. The implementation of AI in biomedical fields faces challenges such as ethical and privacy concerns, lack of awareness, technology unreliability, and professional liability. A brief discussion is given of the AI techniques, which include Virtual screening (VS), DL, ML, Hidden Markov models (HMMs), Neural networks (NNs), Generative models (GMs), Molecular dynamics (MD), and Structure-activity relationship (SAR) models. The study explores the application of AI in biomedical fields, highlighting its enhanced predictive accuracy, treatment efficacy, diagnostic efficiency, faster decision-making, personalised treatment strategies, and precise medical interventions.

Colorectal cancer (CRC) continues to be a major worldwide health issue, with elevated death rates linked to late stages of the illness. Immunotherapy has made significant progress in developing effective techniques to improve the immune system's capacity to identify and eradicate cancerous cells. This study examines the most recent advancements in CAR-T cell treatment and exosome-based immunotherapy for CRC. CAR-T cell therapy, although effective in treating blood cancers, encounters obstacles when used against solid tumours such as CRC. These obstacles include the presence of an immunosuppressive tumour microenvironment and a scarcity of tumour-specific antigens. Nevertheless, novel strategies like dual-receptor CAR-T cells and combination therapy involving cytokines have demonstrated promise in surmounting these obstacles. Exosome-based immunotherapy is a promising approach for targeted delivery of therapeutic drugs to tumour cells, with high specificity and minimal off-target effects. However, there are still obstacles to overcome in the field, such as resistance to treatment, adverse effects associated with the immune system, and the necessity for more individualised methods. The current research is focused on enhancing these therapies, enhancing the results for patients, and ultimately incorporating these innovative immunotherapeutic approaches into the standard treatment protocols for CRC.

Treating burn lesions has always been challenging because any product should be cheap, accessible, and have anti-bacterial commodities and tissue regeneration properties. The green synthesis of magnesium oxide nanoparticles (GS-MgONPs) can create an optimal prospect that is safe with low toxicity in biological tissue and better safety for application while including the antibacterial effect. This recent study aimed to evaluate the effectiveness of burn wound treatment using GS-MgONPs in rats. GS-MgONPs were synthesised for the first time using a Falcaria vulgaris extract (FVE) and characterised. Thirty male Wistar rats were divided into five groups: An untreated group, conventional product treated group, GS-MgONPs (1 wt%), GS-MgONPs (3 wt%) and 5. FVE (1 wt%). Treatments commenced immediately following burn induction and were administered daily for a duration of 21 d. GS-MgONPs showed a spherical morphology with a diameter of less than 100 nm. The NPs (1% and 3 wt%) and FVE demonstrated significant growth inhibition against Staphylococcus aureus while showing no cytotoxic effects on human fibroblast cells. The proposed subjects treated with 1 wt% and 3 wt% GS-MgONPs were able to significantly increase the rate of wound closure (p < 0.05). Histological observations revealed that collagen formation and epithelial regeneration were more pronounced in the groups receiving 1 wt% and 3 wt% MgONPs. These results indicate that GS-MgONPs effectively enhance the regeneration process.

The goal of this study is to assess the potential advantages of utilising methotrexate (MTH), and mangiferin (MFR), in nanoparticulate configuration which is transethosomes (TRS), which could result in increased stability and solubility, as well as improved infiltration into the arthritic tissues under investigation. The synthesised MTH-MFR-TRS demonstrated a particle size of 151.7 nm and a PDI of 0.1199. Additionally, the zeta potential was observed to be favourable at -30.43 mV. Supplementary evaluations were performed, comprising transmission electron microscopy (TEM), confocal microscopy and skin permeation analysis. The CLSM study revealed that the MTH-MFR-TRS gel formulation demonstrated enhanced permeation of MTH and MFR through the skin layers in comparison with MTH-MFR suspension gel. The results of the in vivo investigation indicate that the MTH-MFR-TRS gel displays favourable anti-arthritic characteristics compared to the diclofenac standard gel. The aforementioned phenomenon was evidenced by means of histopathological investigations and radiographic scrutiny. The study at hand has validated the utility of TRS vesicles as a carrier for the transdermal administration of MTH and MFR, thereby offering a promising therapeutic approach for the management of rheumatoid arthritis.

Breast cancer (BC) is a substantial reason for cancer-related mortality among women across the globe. Anastrozole (ANS) is an effective orally administered hormonal therapy for estrogen+ (ER+) BC treatment. However, several side effects and pharmacokinetic limitations restricted its uses in BC treatment. Therefore, this study developed an in situ gelling injectable-loaded silk fibroin (SF)-ANS NPs, which offers sustained drug release and improved pharmacokinetic properties compared to conventional oral formulations. The optimized in situ gel (ISG) incorporated SF-ANS-NPs were developed, and the pharmacokinetic parameters were accessed in subcutaneous administration of NMU-induced Wistar albino rats. The results demonstrated that SF-ANS-NP-ISG exhibited a significantly higher C_max, T_max, and AUC compared to pure ANS suspension. In addition, tumor multiplicity (1.40 ± 0.66), tumor latency (75 ± 9.2 days), and incidence rate (90 ± 2.1%) were recorded, and post-treatment analysis reported a marked reduction in tumor volume and weight compared to positive control within 90 days of a single dose. The SF-ANS-NP-ISG treated group's histopathological assessment indicated a low-grade carcinoma, reduced epithelial hyperplasia, and haemorrhage in mammary tumor tissues compared to positive control. Thus, the SF-ANS-NPs-ISG investigated to overcome the pharmacokinetic limitations of ANS further exhibited targeted delivery and bioavailability compared to conventional techniques.

In recent years, the use of traditional Chinese medicine (TCM) in the treatment of cancer has received widespread attention. Treatment of tumours using TCM can effectively reduce the side effects of anti-tumour drugs, meanwhile to improve the treatment efficacy of patients. However, most of the active ingredients in TCM, such as saponins, alkaloids, flavonoids, volatile oils, etc., have defects such as low bioavailability and poor solubility in clinical application, which seriously restrict the application of TCM. Meanwhile, the encapsulation of TCM into lipid nano-delivery systems for cancer therapy has received much attention. Lipid nano-delivery systems are obtained by using phospholipids as the base material and adding other auxiliary materials under a certain preparation process, including, for example, liposomes, solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), microemulsions, and self-microemulsion drug delivery systems (SMEDDS), can resolve the application problems of TCM by improving the efficacy of active ingredients of TCM and reducing the toxicity of anti-tumour drugs. This paper focuses on the categories, development status, and research progress of lipid nano delivery system of TCM, aiming to provide a certain theoretical basis for further in-depth research and rational application of these systems.

This review delves into the evolving landscape of mediated drug delivery, focusing on the versatility of a variety of drug delivery vehicles such as microspheres, microbots, and nanoparticles (NPs). The review also expounds on the critical components and mechanisms for light-mediated drug delivery, including photosensitizers and light sources such as visible light detectable by the human eye, ultraviolet (UV) light, shorter wavelengths than visible light, and near-infra-red (NIR) light, which has longer wavelength than visible light. This longer wavelength has been implemented in drug delivery for its ability to penetrate deeper tissues and highlighted for its role in precise and controlled drug release. Furthermore, this review discusses the significance of these drug delivery vehicles towards a spectrum of diverse applications spanning gene therapy, cancer treatment, diagnostics, and microsurgery, and the materials used in the fabrication of these vehicles encompassing polymers, ceramics, and lipids. Moreover, the review analyses the challenges and limitations of such drug delivery vehicles as areas of improvement to provide researchers with valuable insights for addressing current obstacles in the progression of drug delivery. Overall, this review underscores the potential of light-mediated drug delivery to revolutionise healthcare and personalised medicine, providing precise, targeted, and effective therapeutic interventions.

The occurrence of oral bone tissue degeneration and bone defects by osteoporosis, tooth extraction, obesity, trauma, and periodontitis are major challenges for clinicians. Traditional bone regeneration methods often come with limitations such as donor site morbidity, limitation of special shape, inflammation, and resorption of the implanted bone. The treatment oriented with biomimetic bone materials has achieved significant attention recently. In the oral bone tissue engineering arena, insulin has gained considerable attention among all the known biomaterials for osteogenesis and angiogenesis. It also exhibits osteogenic and angiogenic properties by interacting with insulin receptors on osteoblasts. Insulin influences bone remodelling both directly and indirectly. It acts directly through the PI3K/Akt and MAPK signalling pathways and indirectly by modulating the RANK/RANKL/OPG pathway, which helps reduce bone resorption. The current review reports the role of insulin in bone remodelling and bone tissue regeneration in the oral cavity in the form of scaffolds and nanomaterials. Different insulin delivery systems, utilising nanomaterials and scaffolds functionalised with polymeric biomaterials have been explored for oral bone tissue regeneration. The review put forward a theoretical basis for future research in insulin delivery in the form of scaffolds and composite materials for oral bone tissue regeneration.