Journal of Drug Targeting最新文献

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.

The geriatric population encompasses the largest part of the health care system worldwide. Chronic medical conditions are highly prevalent in the elderly, consequently, due to their complex health needs, there is a significant rate of multi-drug therapy. Despite the high numbers of medications prescribed, geriatric patients face several barriers when it comes to successful drug delivery including alterations in cognitive and physical function. The current review highlights the impact of chronic diseases on the ageing population along with how changes in drug pharmacokinetics could impact drug efficacy and safety. Also discussed are applications of administration routes in the geriatric population and complications that could arise. A focus is placed on the traditional and upcoming drug delivery advancements being employed in seniors with a focus addressing obstacles faced by this patient category. Nanomedicines, three-dimensional printing, long-acting formulations, transdermal systems, orally disintegrating tablets, and shape/taste modification technologies are discussed. Several barriers to drug delivery in the elderly have been identified in literature and directions for future studies should focus on addressing these gaps for geriatric drug formulation development including personalised medicine, insights into novel drug delivery systems like nanomedicines, methods for decreasing pill burden and shape/size modifications.ARTICLE HIGHLIGHTSTypically, senior citizens take more medications than any other patient population, yet most drug delivery technologies are not tailored to address the specific cognitive and physical barriers that these individuals encounter.The safety of drug delivery systems in the elderly patients should be prioritised with considerations on changes in pharmacokinetics with age, use of non-toxic excipients, and selecting drugs with minimal off-target side effects.Several commercialised and upcoming drug delivery technologies have begun to address the current limitations that the ageing population faces.Future research should focus on applying novel strategies like 3D printing, personalised medicine, and long-acting formulations to improve drug delivery to elderly patients.

Alzheimer's disease (AD), which is marked by gradual neuronal decline and subsequent loss of cognitive functions and memory, poses significant treatment challenges. The present study involved the development, in vitro, and in vivo evaluation of a novel intranasal mucoadhesive in-situ gel of vinpocetine (VIN) with the aim to target the brain. An innovative gel formulation composed of poloxamer 407, HPMC E15 LV, and citric acid as a solubilizer was developed by 2³ Factorial Design. The developed optimal formulation exhibited favorable rheological properties as it displayed ideal gelation time (31.6 ± 1.52 sec), optimum gelling temperature (32 ± 1.0 °C), enhanced mucoadhesive strength (6622 ± 2.64 dynes/cm²), prolonged adhesion (7.22 ± 0.57 hrs) compared with the baseline formulation (F18), and improved drug release in 12 hrs (39.59 ± 1.6%). In vivo, pharmacokinetics revealed a significant increase in C_max (∼2-fold) and AUC_0-t (∼2-fold) in the brain with the in-situ intranasal gel compared to the oral route. In the rat model of AD, in-situ intranasal gel demonstrated significantly greater efficacy (p < 0.001) than oral administration in alleviating AD symptoms as evidenced by behavioral and histological studies. Thus, VIN in-situ gel can be safe and noninvasive for nose-to-brain drug delivery.

Atherosclerosis (AS) is a chronic systemic inflammatory disease, where early diagnosis and theranostics strategy for AS are crucial for improving outcomes. However, conventional diagnostic techniques are limited in identifying early AS lesions, failing to stop the progression of AS in time. Nano-delivery systems have shown significant potential in AS diagnosis and treatment, offering distinct advantages in plaque identification and enhancing drugs concentration at lesion sites, thereby advancing new-generation theranostics strategy. This review discusses the application of nano-delivery systems based on imaging technology in AS diagnosis, and we further explore recent advancements in combining different imaging technologies with emerging theranostics strategy. In addition, we also discuss the challenges faced by nano-delivery systems for AS diagnosis and theranostics in clinical translation, such as nanoparticle targeting efficiency, cytotoxicity and long-term accumulation, immune clearance and inaccurate disease modelling. Finally, we also provide prospects on nano-delivery systems based on diagnostic and therapeutic strategies.