Journal of Drug Targeting最新文献

The worldwide HIV cases were 39.0 million (33.1-45.7 million) in 2022. Due to genetic variations, HIV-1 is more easily transmitted than HIV-2 and favours CD4 + T cells and macrophages, producing AIDS. Conventional HIV drug therapy has many drawbacks, including adherence issues leading to resistance, side effects that lower life quality, drug interactions, high costs limiting global access, inability to eliminate viral reservoirs, chronicity requiring lifelong treatment, emerging toxicities, and a focus on managing infections. Conventional dosage forms have bioavailability issues due to intestinal P-glycoprotein (P-gp) efflux, which can reduce anti-retroviral drug efficacy and lead to resistance. Use of phyto-constituents with P-gp regulating actions has great benefits for semi-synthetic modification to create formulations with greater bioavailability and reduced toxicity, which improves drug effectiveness. Lipid-based nanocarriers, solid lipid nanoparticles, nanostructured lipid carriers, polymer-based nanocarriers, and inorganic nanoparticles may inhibit P-gp efflux. Employing potent P-gp inhibitors within nanocarriers as a Trojan horse approach can enhance the intracellular accumulation of anti-retroviral drugs (ARDs), which are substrates for efflux transporters. This technique increases oral bioavailability and offers lower-dose options, boosting HIV patient compliance and lowering costs. Molecular docking of the inhibitor with P-gp may anticipate optimum binding and function, allowing drug efflux to be minimised.

Cardiovascular diseases (CVDs) are the leading cause of death globally, with oxidative stress (OS) identified as a primary contributor to their onset and progression. Given the elevated incidence and mortality rates associated with CVDs, there is an imperative need to investigate novel therapeutic strategies. Nuclear factor erythroid 2-related factor 2 (Nrf2), ubiquitously expressed in the cardiovascular system, has emerged as a promising therapeutic target for CVDs due to its role in regulating OS and inflammation. This review aims to delve into the mechanisms and actions of the Nrf2 pathway, highlighting its potential in mitigating the pathogenesis of CVDs.

Nanoparticles (NPs) have played a pivotal role in various biomedical applications, spanning from sensing to drug delivery, imaging and anti-viral therapy. The therapeutic utilisation of NPs in clinical trials was established in the early 1990s. Silver nanoparticles (AgNPs) possess anti-microbial, anti-cancer and anti-viral properties, which make them a possible anti-viral drug to combat the COVID-19 virus. Free radicals and reactive oxygen species are produced by AgNPs, which causes apoptosis induction and prevents viral contamination. The shape and size of AgNPs can influence their interactions and biological activities. Therefore, it is recommended that silver nanoparticles (AgNPs) be used as a valuable tool in the management of COVID-19 pandemic. These nanoparticles possess strong anti-microbial properties, allowing them to penetrate and destroy microbial cells. Additionally, the toxicity level of nanoparticles depends on the administered dose, and surface modifications are necessary to reduce toxicity, preventing direct interaction between metal surfaces and cells. By utilising silver nanoparticles, drugs can be targeted to specific areas in the body. For example, in the case of COVID-19, anti-viral drugs can be stimulated as nanoparticles in the lungs to accelerate disease recovery. Nanoparticle-based systems have the capability to transport drugs and treat specific body parts. This review offers an examination of silver nanoparticle-based drug delivery systems for combatting COVID-19, with the objective of boosting the bioavailability of existing medications, decreasing their toxicity and raising their efficiency.

N-doped carbon quantum dot (CQD) nanoparticle was prepared as a novel nanocarrier with excellent solubility, stability, and high quantum yield to overcome Indocyanine Green (ICG) obstacle in photodynamic therapy (PDT) with simultaneous cell imaging property. Cell culture study and In vivo assessments on the C57BL/6 mice containing melanoma cancer cells was performed. Results showed that CQD size after ICG loading slightly enhanced from 24.55 nm to 42.67 nm. Detection of reactive oxygen species (ROS) test demonstrated that CQD improved ICG photo-stability and ROS generation capacity upon laser irradiation. Cell culture study illustrated that ICG@CQD could decrease the survival rate of melanoma cancer cells of B16F10 cell line from 48% for pure ICG drug to 28% for ICG@CQD. Captured images by confocal microscopy approved more cellular uptake of ICG@CQD and more qualified cell imaging ability of the nanocarrier. In vivo assessments on the C57BL/6 mice containing melanoma cancer cells displayed the obvious inhibitory effect of the tumor growth for ICG@CQD in comparison to free ICG. In vivo fluorescence images confirmed that ICG@CQD accumulates remarkably more than free ICG in the tumor region. In conclusion, ICG@CQD is proposed as an innovative nanocarrier with great potential for PDT and diagnosis.

Breast cancer presents a significant global health challenge, ranking highest incidence rate among all types of cancers. Functionalised nanocarriers offer a promising solution for precise drug delivery by actively targeting cancer cells through specific receptors, notably folate receptors. By overcoming the limitations of passive targeting in conventional therapies, this approach holds the potential for enhanced treatment efficacy through combination therapy. Encouraging outcomes from studies like in vitro and in vivo, underscore the promise of this innovative approach. This review explores the therapeutic potential of FA (Folic acid) functionalised nanocarriers tailored for breast cancer management, discussing various chemical modification techniques for functionalization. It examines FA-conjugated nanocarriers containing chemotherapeutics to enhance treatment efficacy and addresses the pharmacokinetic aspect of these functionalised nanocarriers. Additionally, the review integrates active targeting via folic acid with theranostics, photothermal therapy, and photodynamic therapy, offering a comprehensive management strategy. Emphasising rigorous experimental validation for practical utility, the review underscores the need to bridge laboratory research to clinical application. While these functionalised nanocarriers show promise, their credibility and applicability in real-world settings necessitate thorough validation for effective clinical use.

The World Health Organization (WHO) reported that of all the non-communicable diseases, cancer is considered the second cause of death worldwide. This has driven the big pharma companies to prioritise anticancer products in their pipeline. In addition, research has focused on exploration of new anticancer molecules and design of suitable dosage forms to achieve effective drug delivery to the tumour site. Nanotechnology is a valuable tool to build nano delivery systems with controlled and targeted drug release properties. Nanoparticles can be fabricated by robust, scalable and economic techniques using various polymers. Moreover, specific functional groups can be introduced to the surface of nanoparticles enabling targeting to a specific tissue; besides, they exhibit versatile drug release patterns according to the rate of polymer degradation. This review outlines the processes and advances in surface functionalisation of nanoparticles employed for treatment of breast cancer. The therapeutic molecules, the polymers used to fabricate nanoparticles, the techniques used to prepare the nanoparticles have been reviewed with a focus on the processes employed to functionalise these nanoparticles with suitable ligands to target different types of breast cancer.

Ferroptosis is a novel form of programmed cell death that is iron-dependent and distinct from autophagy, apoptosis, and necroptosis. It is primarily characterised by a decrease in glutathione peroxidase 4 (GPX4) activity, or by the accumulation of lipid peroxidation and reactive oxygen species (ROS). Renal fibrosis is a common pathological change in the progression of various primary and secondary renal diseases to end-stage renal disease and poses a serious threat to human health with high morbidity and mortality. Multiple pathways contribute to the development of renal fibrosis, with ferroptosis playing a crucial role in renal fibrosis pathogenesis due to its involvement in the production of ROS. Ferroptosis is related to several signalling pathways, including System Xc-/GPX4, abnormal iron metabolism and lipid peroxidation. A number of studies have indicated that ferroptosis is closely involved in the process of renal fibrosis caused by various kidney diseases such as glomerulonephritis, renal ischaemia-reperfusion injury, diabetic nephropathy and renal calculus. Identifying the underlying molecular mechanisms that determine cell death would open up new insights to address a therapeutic strategy to renal fibrosis. The review aimed to browse and summarise the known mechanisms of ferroptosis that may be associated with biological reactions of renal fibrosis.