Virulence traits and novel drug delivery strategies for mucormycosis post-COVID-19: a comprehensive review

The outbreak of a fatal black fungus infection after the resurgence of the cadaverous COVID-19 has exhorted scientists worldwide to develop a nutshell by repurposing or designing new formulations to address the crisis. Patients expressing COVID-19 are more susceptible to Mucormycosis (MCR) and thus fall easy prey to decease accounting for this global threat. Their mortality rates range around 32-70% depending on the organs affected and grow even higher despite the treatment. The many contemporary recommendations strongly advise using liposomal amphotericin B and surgery as first-line therapy whenever practicable. MCR is a dangerous infection that requires an antifungal drug administration on appropriate prescription, typically one of the following: Amphotericin B, Posaconazole, or Isavuconazole since the fungi that cause MCR are resistant to other medications like fluconazole, voriconazole, and echinocandins. Amphotericin B and Posaconazole are administered through veins (intravenously), and isavuconazole by mouth (orally). From last several years so many compounds are developed against invasive fungal disease but only few of them are able to induce effective treatment against the micorals. Adjuvant medicines, more particularly, are difficult to assess without prospective randomized controlled investigations, which are challenging to conduct given the lower incidence and higher mortality from Mucormycosis. The present analysis provides insight into pathogenesis, epidemiology, clinical manifestations, underlying fungal virulence, and growth mechanisms. In addition, current therapy for MCR in Post Covid-19 individuals includes conventional and novel nano-based advanced management systems for procuring against deadly fungal infection. The study urges involving nanomedicine to prevent fungal growth at the commencement of infection, delay the progression, and mitigate fatality risk

COMPASSIONATE USE OF INVESTIGATIONAL DRUG DURING EMERGENCY CONDITIONS AND ASSOCIATED ETHICAL ASPECTS, CHALLENGES, AND BENEFITS

“Compassionate Use,” also known as expanded access, is a method by which patients with a life-threatening or seriously debilitating disease that has no satisfactory treatment alternatives can gain access to new drugs outside the context of a clinical trial. Compassionate use (CU) of unlicensed drugs serves the need of patients with the serious debilitating disease in the absence of alternative approved therapies. CU does allow limited access to new products currently in clinical trials. However, it must be remembered that there are strict guidelines to follow. As with any new drug-device or treatment, there are strict guidelines determined by the Food and Drug Administration and study sponsor, especially for CU. This article contains the use of an investigational drug in emergencies, which are the ethical aspects for getting approval, the major challenges in taking a compassionate drug, and the benefits for dying patients

Nanodelivery systems: An efficient and target‐specific approach for drug‐resistant cancers

Abstract Background Cancer treatment is still a global health challenge. Nowadays, chemotherapy is widely applied for treating cancer and reducing its burden. However, its application might be in accordance with various adverse effects by exposing the healthy tissues and multidrug resistance (MDR), leading to disease relapse or metastasis. In addition, due to tumor heterogeneity and the varied pharmacokinetic features of prescribed drugs, combination therapy has only shown modestly improved results in MDR malignancies. Nanotechnology has been explored as a potential tool for cancer treatment, due to the efficiency of nanoparticles to function as a vehicle for drug delivery. Methods With this viewpoint, functionalized nanosystems have been investigated as a potential strategy to overcome drug resistance. Results This approach aims to improve the efficacy of anticancer medicines while decreasing their associated side effects through a range of mechanisms, such as bypassing drug efflux, controlling drug release, and disrupting metabolism. This review discusses the MDR mechanisms contributing to therapeutic failure, the most cutting‐edge approaches used in nanomedicine to create and assess nanocarriers, and designed nanomedicine to counteract MDR with emphasis on recent developments, their potential, and limitations. Conclusions Studies have shown that nanoparticle‐mediated drug delivery confers distinct benefits over traditional pharmaceuticals, including improved biocompatibility, stability, permeability, retention effect, and targeting capabilities

It’s all in the noise: A review of noise stress on gastric secretions via the stimulation of corticosteroids and management options

One of the toughest sources of restrictions on the environment and the workplace is noise. Numerous impacts of noise on the immune system, hormone levels, and the cardiovascular and pulmonary systems have been well recognized. In this regard, noise induced stress imparts a very serious effect on the body and is considered one of the richest elements of pollution in the environment. It is well documented in the research arena that noise affects immune function, hormonal levels, and the cardiovascular and respiratory systems through the secretion of hormones and other biomolecules. For example, the excessive secretion of acids leads to an acidic bounce or the peptic juice over secretion that can end with gastric as well as the peptic ulcers. This review article was focused on the latest information concerning gastric acid secretion through noise induced corticosteroid hormones. The pathophysiology of noise stress-induced disorders is heavily influenced by the disruption of the brain-gut axis. Noise stress enhances visceral sensitivity, affects gastrointestinal (GI) motility, increases intestinal permeability, and profoundly activates mast cells, which release a variety of proinflammatory mediators. The main aim here is to make clear that the effects of noise of varying intensities can alter gastric stimulation and key health issues so that the medical community can focus on probable treatment options, something that has not been acknowledged in medicine to date

Radiopharmaceuticals: navigating the frontier of precision medicine and therapeutic innovation

Abstract This review article explores the dynamic field of radiopharmaceuticals, where innovative developments arise from combining radioisotopes and pharmaceuticals, opening up exciting therapeutic possibilities. The in-depth exploration covers targeted drug delivery, delving into passive targeting through enhanced permeability and retention, as well as active targeting using ligand-receptor strategies. The article also discusses stimulus-responsive release systems, which orchestrate controlled release, enhancing precision and therapeutic effectiveness. A significant focus is placed on the crucial role of radiopharmaceuticals in medical imaging and theranostics, highlighting their contribution to diagnostic accuracy and image-guided curative interventions. The review emphasizes safety considerations and strategies for mitigating side effects, providing valuable insights into addressing challenges and achieving precise drug delivery. Looking ahead, the article discusses nanoparticle formulations as cutting-edge innovations in next-generation radiopharmaceuticals, showcasing their potential applications. Real-world examples are presented through case studies, including the use of radiolabelled antibodies for solid tumors, peptide receptor radionuclide therapy for neuroendocrine tumors, and the intricate management of bone metastases. The concluding perspective envisions the future trajectory of radiopharmaceuticals, anticipating a harmonious integration of precision medicine and artificial intelligence. This vision foresees an era where therapeutic precision aligns seamlessly with scientific advancements, ushering in a new epoch marked by the fusion of therapeutic resonance and visionary progress. Graphical Abstrac

Multi drug resistance in Colorectal Cancer- approaches to overcome, advancements and future success

A significant obstacle to treating cancer is multidrug resistance (MDR), which is the capacity of cancerous cells to develop resistance to both traditional and cutting-edge chemotherapeutic treatments. Following the initial discovery that cellular pumps reliant on ATP were the root of chemotherapy resistance, more research has revealed the involvement of additional mechanisms, including increased drug metabolism, reduced drug entry, and compromised apoptotic pathways. Numerous projects have focused on MDR, and innumerable research has been conducted to better understand MDR and develop methods to mitigate its consequences. Multidrug resistance (MDR) is a key challenge in treating cancer. 90% of cancer-related fatalities are brought on by tumor metastasis and recurrence, which is possible with MDR. Drug resistance in cancerous cells is influenced by diverse internal and extrinsic variables, including genetic and epigenetic changes, drug efflux systems, DNA repair mechanisms, apoptosis, and autophagy. In this review paper, we list the potential hazards associated with cancer therapy in general, primarily multidrug resistance developing a theory for colorectal cancer in particular. We discussed the unique instance of multidrug resistance in colorectal cancer in malignancies generally and 5-fluorouracil, curcumin, and lipids as viable therapy options for the condition. The use of nanotechnology (mainly nanoparticles) has facilitated better in vitro as well as in vivo efficacy during preclinical phases, summarized below, allowing for a more thorough investigation of colorectal cancers and pancreatic carcinomas with their translation to following clinical trials

Overview of processed excipients in ocular drug delivery: Opportunities so far and bottlenecks

Ocular drug delivery presents a unique set of challenges owing to the complex anatomy and physiology of the eye. Processed excipients have emerged as crucial components in overcoming these challenges and improving the efficacy and safety of ocular drug delivery systems. This comprehensive overview examines the opportunities that processed excipients offer in enhancing drug delivery to the eye. By analyzing the current landscape, this review highlights the successful applications of processed excipients, such as micro- and nano-formulations, sustained-release systems, and targeted delivery strategies. Furthermore, this article delves into the bottlenecks that have impeded the widespread adoption of these excipients, including formulation stability, biocompatibility, regulatory constraints, and cost-effectiveness. Through a critical evaluation of existing research and industry practices, this review aims to provide insights into the potential avenues for innovation and development in ocular drug delivery, with a focus on addressing the existing challenges associated with processed excipients. This synthesis contributes to a deeper understanding of the promising role of processed excipients in improving ocular drug delivery systems and encourages further research and development in this rapidly evolving field

A narrative review on the role of magnesium in immune regulation, inflammation, infectious diseases, and cancer

Abstract Background Magnesium (Mg) has gained much importance recently because of its unique range of biological functions. It is one of the most significant micronutrients in biological systems. This review aims to outline the immune-regulating actions of Mg and its crucial role in regulating inflammation and immune response to infectious agents and malignancies. Methods We conducted a literature review on MEDLINE, PubMed, EMBASE, Web of Science to determine the impact of Mg on immune regulation in three settings of inflammation, infection, and cancer. We thoroughly examined all abstracts and full-text articles and selected the most relevant ones for inclusion in this review. Results Mg has long been associated with immunological responses, both nonspecific and specific. It plays a pivotal role in diverse immune responses by participating in multiple mechanisms. It facilitates substance P binding to lymphoblasts, promotes T helper, B cell, and macrophage responses to lymphokines, and facilitates antibody-dependent cytolysis and immune cell adherence. Besides, Mg serves as a cofactor for C'3 convertase and immunoglobulin synthesis. It additionally boasts a significant anti-cancer effect. Chronic Mg deficiency leads to enhanced baseline inflammation associated with oxidative stress, related to various age-associated morbidities. A deficiency of Mg in rodents has been observed to impact the cell-mediated immunity and synthesis of IgG adversely. This deficiency can lead to various complications, such as lymphoma, histaminosis, hypereosinophilia, increased levels of IgE, and atrophy of the thymus. The immunological consequences of Mg deficiency in humans can be influenced by the genetic regulation of Mg levels in blood cells. Mg can also mediate cell cycle progression. There has been a renewed interest in the physiology and therapeutic efficacy of Mg. However, the in-depth mechanisms, their clinical significance, and their importance in malignancies and inflammatory disorders still need to be clarified. Conclusions Mg is essential for optimal immune function and regulating inflammation. Deficiency in Mg can lead to temporary or long-term immune dysfunction. A balanced diet usually provides sufficient Mg, but supplementation may be necessary in some cases. Excessive supplementation can have negative impacts on immune function and should be avoided. This review provides an update on the importance of Mg in an immune response against cancer cells and infectious agents and how it regulates inflammation, oxidative stress, cell progression, differentiation, and apoptosis

Potentially active aspirin derivative to release nitric oxide: In-vitro, in-vivo and in-silico approaches

The series of newer salicylate derivatives incorporating nitroxy functionality were synthesized and evaluated for their potential effect in gastrointestinal (GI) related toxicity produced by aspirin. The synthesized compounds (5a-j) were subjected to %NO (nitric oxide) release study, in-vitro anti-inflammatory potential, % inhibition of carrageenan-induced paw edema and the obtained results were validated by in-silico studies including molecular docking, MD simulations and in-silico ADME (absorption, distribution, metabolism, and elimination) calculations. Compounds 5a (20.86 %) and 5g (18.20 %) displayed the highest percentage of NO release in all the tested compounds. Similarly, 5a and 5h were found to have (77.11 % and 79.53 %) &(78.56 % and 66.10 %) inhibition in carrageenan induced paw edema in animal mode which were relatively higher than ibuprofen (standard used). The obtained results were validated by molecular docking and MD simulations studies. The molecular docking study of 5a and 5h revealed that docking scores were also obtained in very close proximity of −8.35, −9.67 and −8.48 for ibuprofen, 5g and 5h respectively. In MD simulations studies, the calculated lower RMSD (root mean square deviation) values 2.8 Å and 5.6 Å for 5g and 5h, respectively indicated the stability of ligand-protein complexes. Similarly lower RSMF (root mean square fluctuation) values indicated the molecules remained in the active pocket throughout the entire MD simulations run. Further, in-silico ADME calculations were determined and all compounds obey the Lipinski’s rule of five and it was predicted that these molecules would be orally active without any serious toxic effect