Journal of Drug Targeting最新文献

Vascular neogenesis, an early event in the development of rheumatoid arthritis (RA) inflammation, is critical for the formation of synovial vascular networks and plays a key role in the progression and persistence of chronic RA inflammation. microRNAs (miRNAs), a class of single-stranded, non-coding RNAs with approximately 21-23 nucleotides in length, regulate gene expression by binding to the 3' untranslated region (3'-UTR) of specific mRNAs. Increasing evidence suggests that miRNAs are differently expressed in diseases associated with vascular neogenesis and play a crucial role in disease-related vascular neogenesis. However, current studies are not sufficient and further experimental studies are needed to validate and establish the relationship between miRNAs and diseases associated with vascular neogenesis, and to determine the specific role of miRNAs in vascular development pathways. To better treat vascular neogenesis in diseases such as RA, we need additional studies on the role of miRNAs and their target genes in vascular development, and to provide more strategic references. In addition, future studies can use modern biotechnological methods such as proteomics and transcriptomics to investigate the expression and regulatory mechanisms of miRNAs, providing a more comprehensive and in-depth research basis for the treatment of related diseases such as RA.

Cardiovascular disease is the leading cause of death worldwide, and it's of great importance to understand its underlying mechanisms and find new treatments. Sphingosine 1-phosphate (S1P) is an active lipid that exerts its effects through S1P receptors on the cell surface or intracellular signal, and regulates many cellular processes such as cell growth, cell proliferation, cell migration, cell survival, and so on. S1PR modulators are a class of modulators that can interact with S1PR subtypes to activate receptors or block their activity, exerting either agonist or functional antagonist effects. Many studies have shown that S1P plays a protective role in the cardiovascular system and regulates cardiac physiological functions mainly through interaction with cell surface S1P receptors (S1PRs). Therefore, S1PR modulators may play a therapeutic role in cardiovascular diseases. Here, we review five S1PRs and their functions and the progress of S1PR modulators. In addition, we focus on the effects of S1PR modulators on atherosclerosis, myocardial infarction, myocardial ischaemia/reperfusion injury, diabetic cardiovascular diseases, and myocarditis, which may provide valuable insights into potential therapeutic strategies for cardiovascular disease.

Efferocytosis refers to the process by which phagocytes remove apoptotic cells and related apoptotic products. It is essential for the growth and development of the body, the repair of damaged or inflamed tissues, and the balance of the immune system. Damaged efferocytosis will cause a variety of chronic inflammation and immune system diseases. Many studies show that efferocytosis is a process mediated by mitochondria. Mitochondrial metabolism, mitochondrial dynamics, and communication between mitochondria and other organelles can all affect phagocytes' clearance of apoptotic cells. Therefore, targeting mitochondria to modulate phagocyte efferocytosis is an anticipated strategy to prevent and treat chronic inflammatory diseases and autoimmune diseases. In this review, we introduced the mechanism of efferocytosis and the pivoted role of mitochondria in efferocytosis. In addition, we focused on the therapeutic implication of drugs targeting mitochondria in diseases related to efferocytosis dysfunction.

Nanotechnology has significantly impacted human life, particularly in overcoming the limitations associated with neurodegenerative diseases (NDs). Various nanostructures and vehicle systems, such as polymer nanoparticles, carbon nanotubes (CNTs), nanoliposomes, nano-micelles, lipid nanoparticles, lactoferrin, polybutylcyanoacrylate, and poly lactic-co-glycolic acid, have been shown to enhance drug efficacy, reduce side effects, and improve pharmacokinetics. NDs affect millions worldwide and are challenging to treat due to the blood-brain barrier (BBB), which hinders drug delivery to the central nervous system (CNS). Research suggests that natural ingredients can be formulated into nanoparticles, offering a promising approach for ND treatment. This review examines the advantages and disadvantages of herbal-based nanoformulations, highlighting their potential effectiveness when used alone or in combination with other medications. Herbal nanoparticles provide benefits over synthetic ones due to their biocompatibility, reduced toxicity, and potential for synergistic effects. The study's findings can be applied to develop more efficient drug delivery systems, improving the treatment of NDs by enhancing drug penetration across the BBB and targeting affected CNS areas more precisely.

Cancer has a devastating impact globally regardless of gender, age, and community, which continues its severity to the population due to the lack of efficient strategy for the cancer diagnosis and treatment. According to the World Health Organisation report, one out of six people dies due to this deadly cancer and we need effective strategies to regulate it. In this context, trace element has a very hidden and unexplored role and require more attention from investigators. The variation in concentration of trace elements was observed during comparative studies on a cancer patient and a healthy person making them an effective target for cancer regulation. The percentage of trace elements present in the human body depends on environmental exposure, food habits, and habitats and could be instrumental in the early diagnosis of cancer. In this review, we have conducted inclusive analytics on trace elements associated with the various types of cancers and explored the several methods involved in their analysis. Further, intricacies in the correlation of trace elements with prominent cancers like prostate cancer, breast cancer, and leukaemia are represented in this review. This comprehensive information on trace elements proposes their role during cancer and as biomarkers in cancer diagnosis.

Cancer is a leading cause of death worldwide, and imposes a substantial socioeconomic burden with little impact especially on aggressive types of cancer. Conventional therapies have many serious side effects including generalised systemic toxicity which limits their long-term use. Tumour resistance and recurrence is another main problem associated with conventional therapy. Purified or extracted natural products have been investigated as cost-effective cancer chemoprotective agents with the potential to reverse or delaying carcinogenesis. Curcumin (CUR) as a natural polyphenolic component, exhibits many pharmacological activities such as anti-cancer, anti-inflammatory, anti-microbial, activity against neurodegenerative diseases including Alzheimer, antidiabetic activities (type II diabetes), anticoagulant properties, wound healing effects in both preclinical and clinical studies. Despite these effective protective properties, CUR has several limitations, including poor aqueous solubility, low bioavailability, chemical instability, rapid metabolism and a short half-life time. To overcome the pharmaceutical problems associated with free CUR, novel nanomedicine strategies (including polymeric nanoparticles (NPs) such as poly (lactic-co-glycolic acid) (PLGA) NPs have been developed. These formulations have the potential to improve the therapeutic efficacy of curcuminoids. In this review, we comprehensively summarise and discuss recent in vitro and in vivo studies to explore the pharmaceutical significance and clinical benefits of PLGA-NPs delivery system to improve the efficacy of CUR in the treatment of cancer.

Background and objective: Researchers have put in significant laboratory time and effort in measuring the permeability coefficient (Kp) of xenobiotics. To develop alternative approaches to this labour-intensive procedure, predictive models have been employed by scientists to describe the transport of xenobiotics across the skin. Most quantitative structure-permeability relationship (QSPR) models are derived statistically from experimental data. Recently, artificial intelligence-based computational drug delivery has attracted tremendous interest. Deep learning is an umbrella term for machine-learning algorithms consisting of deep neural networks (DNNs). Distinct network architectures, like convolutional neural networks (CNNs), feedforward neural networks (FNNs), and recurrent neural networks (RNNs), can be employed for prediction.

Methods: In this project, we used a convolutional neural network, feedforward neural network, and recurrent neural network to predict skin permeability coefficients from a publicly available database reported by Cheruvu et al. The dataset contains 476 records of 145 chemicals, xenobiotics, and pharmaceuticals, administered on the human epidermis in vitro from aqueous solutions of constant concentration either saturated in infinite dose quantities or diluted. All the computations were conducted with Python under Anaconda and Jupyterlab environment after importing the required Python, Keras, and Tensorflow modules.

Results: We used a convolutional neural network, feedforward neural network, and recurrent neural network to predict log kp.

Conclusion: This research work shows that deep learning networks can be successfully used to digitally screen and predict the skin permeability of xenobiotics.

Introduction: The search for fast and efficient treatment for dermonecrotic lesions caused by the venom of the spider from the Loxosceles simillis, is a demand in health. Prednisolone is one of the most used drugs, however it has side effects. In this context, addictionally gold nanoparticles (GNPs) have anti-inflammatory, antioxidant, and antibacterial properties. The use of photobiomodulation has show to be efficient in the process of tissue repair. Therefore, the purpose of this study was to investigate the anti-inflammatory effect of photobiomodulation and GNPs associated or not with a low concentration of prednisolone in animal models of dermonecrotic lesion.Methodology: For this, rabbits with venon-induced dermonecrotic lesion were subjected to topical treatment with prednisolone + laser or GNPs + laser or Pred-GNPs + laser. The area of edema, necrosis and erythema were measured. On the last day of treatment, the animals were euthanized to remove the organs for histopathological and biochemical analysis.Results: All treatments combinations were effective in promoting the reduction of necrotic tissue and erythema.Conclusion: With this results, we suggest that the use of laser and nanoparticles, associated or not with prednisolone, should be considered for the treatment of dermonecrotic injury.

Pharmaceutical cocrystals, owing to their manifold applications, are acting as bridge between drug discovery and pharmaceutical product development. The ability to scale up pharmaceutical cocrystals through continuous manufacturing approaches offers superior and economic pharmaceutical products. Moreover, cocrystals can be an aid for the nanoparticulate systems to solve the issues related to scale-up and cost. Cocrystals grabbed attention of academic researchers and pharmaceutical scientist due to their potential to target various diseases like cancer. The present review is mainly focussed on the diverse and comprehensive applications of pharmaceutical cocrystals in drug delivery including solubility and dissolution enhancement, improvement of bioavailability of drug, mechanical and flow properties of active pharmaceutical ingredients, controlled/sustained release and colour tuning of API. Besides, phytochemical based cocrystals, multi-drug cocrystals and cocrystals for tumour therapy have been discussed in this review. Additionally, recent progress pertinent to pharmaceutical cocrystals is also included, which may provide future directions to manufacturing and scale-up of cocrystals.

Aims: Nerve growth factor is a well characterised neurotrophic factor that play a critical role in the survival, growth and differentiation of neurons both in central and peripheral nervous system. However, it is difficult for the conventional exogenous nerve growth factor administration delivery to the central nervous system due to the biological barrier in human bodies.Results: We validated a series of cell penetrating peptides and found that L-PenetraMax significantly enhanced the efficiency of recombinant human nerve growth factor entry into the rat retina. In the optic nerve crush mice model, eye drop administration of recombinant human nerve growth factor alone promoted retinal ganglion cell survival and axon regeneration at high dose, while the combination of recombinant human nerve growth factor with L-PenetraMax significantly enhanced the neuroprotective efficacy at lower dose, thus potentially enhancing the availability of recombinant human nerve growth factor eye drops in patients with optic neuropathy.Conclusions: This study provides the evidence that the noncovalent coadministration of recombinant human nerve growth factor with L-PenetraMax could be a potent strategy for the non-invasive and sustained ocular delivery of therapeutic proteins for improving the optic nerve injury.