Browsing by Author "Dua, K."
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- ItemA new era in oxygen therapeutics?: from perfluorocarbon systems to haemoglobin-based oxygen carriers(Churchill Livingstone, 2022) Charbe, N.B.; Castillo, F.; Tambuwala, M.M.; Chellappan, D.K.; Carreño, A.; Satija, S.; Singh, S.K.; Gulati, M.; Dua, K.; Gonzalez-Aramundiz, J.V.Blood transfusion is the key to life in case of traumatic emergencies, surgeries and in several pathological conditions. An important goal of whole blood or red blood cell transfusion is the fast delivery of oxygen to vital organs and restoration of circulation volume. Whole blood or red blood cell transfusion has several limitations. Free haemoglobin not only loses its tetrameric configuration and extracts via the kidney leading to nephrotoxicity but also scavenges nitric oxide (NO), leading to vasoconstriction and hypertension. PFC based formulations transport oxygen in vivo, the contribution in terms of clinical outcome is challenging. The oxygen-carrying capacity is not the only criterion for the successful development of haemoglobin-based oxygen carriers (HBOCs). This review is a bird's eye view on the present state of the PFCs and HBOCs in which we analyzed the current modifications made or which are underway in development, their promises, and hurdles in clinical implementation.
- ItemBiological databases and tools for neurological disorders(IMR Press Limited, 2022) Usman, M.B.; Ojha, S.; Jha, S.K.; Chellappan, D.K.; Gupta, G.; Singh, S.K.; Dua, K.; Roychoudhury, S.; Kumar, N.; Khan, F.A.; Dureja, H.; Upadhye, V.; Zacconi, Flavia C. M.; Prasanna, P.; Kesari, K.K.; Ashraf, G.M.; Alexiou, A.; Jha, N.K.Computational approaches to study of neuronal impairment is rapidly evolving, as experiments and intuition alone do not explain the complexity of the brain system. An overwhelming increase in the amount of new data from both theory and computational modeling necessitate the development of databases and tools for analysis, visualization and interpretation of neuroscience data. To ensure the sustainability of this development, consistent update and training of young professionals is imperative. For this purpose, relevant articles, chapters, and modules are essential to keep abreast of developments. This review seeks to outline the biological databases and analytical tools along with their applications. It is envisaged that such knowledge could provide a ''training recipe'' for young scientists and a guide for professionals and researchers in neuroscience.
- ItemChitosan modified 5-fluorouracil nanostructured lipid carriers for treatment of diabetic retinopathy in rats: a new dimension to an anticancer drug(Elsevier B.V., 2022) Sharma, D.S.; Wadhwa, S.; Gulati, M.; Kumar, B.; Vishwas, S.; Khursheed, R.; Saini, S.; Kumar, A.; Parveen, S.R.; Singh, S.K.; Dua, K.; Chitranshi, N.; Gupta, V.K.; Alrouji, M.; Alhajlah, S.; AlOmeir, O.; Gupta, G.; Zacconi, Flavia C. M.; Chellappan, D.K.; Morris, A.; Loebenberg, R.Diabetic retinopathy (DR) is one of the chronic complications of diabetes. It includes retinal blood vessels' damage. If untreated, it leads to loss of vision. The existing treatment strategies for DR are expensive, invasive, and need expertise during administration. Hence, there is a need to develop a non-invasive topical formulation that can penetrate deep to the posterior segment of retina and treat the damaged retinal vessels. In addition, it should also provide sustained release. In recent years, novel drug delivery systems (NDDS) have been explored for treating DR and found successful. In this study, chitosan (CS) modified 5-Fluorouracil Nanostructured Lipid Carriers (CS-5-FU-NLCs) were prepared by modified melt emulsification-ultrasonication method and optimized by Box-Behnken Design. The size, polydispersity index, zeta potential and entrapment efficiency of CS-5-FU-NLCs were 163.2 ± 2.3 nm, 0.28 ± 1.52, 21.4 ± 0.5 mV and 85.0 ± 0.2 %, respectively. The in vitro drug release and ex vivo permeation study confirmed higher and sustained drug release in CS-5-FU-NLCs as compared to 5-FU solution. HET-CAM Model ensured the non-irritant nature of CS-5-FU-NLCs. In vivo ocular studies of CS-5-FU-NLCs confirmed antiangiogenic effect of 5-FU by CAM model and diabetic retinopathy induced rat model, indicating successful delivery of 5-FU to the retina.
- ItemHybrid molecules based on 1,3,5-triazine as potential therapeutics: A focused review(2020) Prasher, P.; Sharma, M.; Aljabali, Alaa A. A.; Gupta, G.; Negi, P.; Kapoor, D. N.; Singh, I.; Zacconi, Flavia C. M.; Andreoli Pinto, T. de J.; Webba da Silva, M.; Bakshi, H.; Chellappan, D. K.; Tambuwala, M. M.; Dua, K.Majority of the representative drugs customarily interact with multiple targets manifesting unintended side effects. In addition, drug resistance and over expression of the cellular efflux-pumps render certain classes of drugs ineffective. With only a few innovative formulations in development, it is necessary to identify pharmacophores and novel strategies for creating new drugs. The conjugation of dissimilar pharmacophoric moieties to design hybrid molecules with an attractive therapeutic profile is an emerging paradigm in the contemporary drug development regime. The recent decade witnessed the remarkable biological potential of 1,3,5-triazine framework in the development of various chemotherapeutics. The appending of the 1,3,5-triazine nucleus to biologically relevant moieties has delivered exciting results. The present review focuses on 1,3,5-triazine based hybrid molecules in the development of pharmaceuticals.
- ItemMultifaceted role of synbiotics as nutraceuticals, therapeutics and carrier for drug delivery(Elsevier Ireland Ltd, 2022) Khursheed, R.; Gulati, M.; Wadhwa, S.; Vishwas, S.; Sharma, D.S.; Corrie, L.; Singh, S.K.; Steel, A.; Adams, J.; Dua, K.; Alam, A.; Alnasser, S.M.; Aba, Alkhayl F.F.; Parveen, Z.; Nammi, S.; Chellappan, D.K.; Gupta, G.; Zacconi, Flavia C. M.; Jha, N.K.Synbiotics, are a combination of probiotics and prebiotics. They play an important role in metabolizing different nutritional substrates and thus helps in the maintenance of human health. Any disbalance in the gut microflora, known as dysbiosis, is known to lead to a number of diseased conditions. It can be reverted by the administration of synbiotics. Present review highlights various mechanistic pathways through which synbiotics act as therapeutics. The dual role of synbiotics as nutraceutical and excipient in developing oral formulations are entailed with case studies. The findings entailed that there exist numerous studies on prebiotics as well as probiotics have been carried out to show their effects in several diseases. However, the concept of combining together them for prevention and treatment of various pathological conditions accruing from dysbiosis is relatively new. Synbiotics, however, face challenge of low stability during their sojourn in the GIT, which is generally overcome by various encapsulation techniques. Various studies also showed potential role of synbiotics in drug delivery. However, it is an emerging area and lacks clinical correlation. It is important to focus on clinical trials of formulations wherein synbiotics have been used as therapeutic moiety as well as pharmaceutical carrier for treating various diseases.
- ItemRutin-loaded liquid crystalline nanoparticles attenuate oxidative stress in bronchial epithelial cells: a PCR validation(2021) Zacconi, Flavia C. M.; Chellappan, D. K.; Dureja, H.; Dua, K.; Raj Paudel, K. R.; Shastri, M. D.; Mehta, M.; Gulati, M.; Hansbro, P.; Singh, S. K.; Satija, S.; Shukla, S. D.Aim: In the present study, the inhibitory potential of rutin-loaded liquid crystalline nanoparticles (LCNs) on oxidative stress was determined in human bronchial epithelial cells (BEAS-2B) by analysing the expression levels of different antioxidant (NADPH quinine oxidoreductase-1 (NQO1); gamma-glutamyl cysteine synthetase catalytic subunit (GCLC)) and pro-oxidant (NADPH oxidase (Nox)-4; Nox2B) genes. Results: Our findings revealed that the rutin-loaded LCNs inhibited the genes, namely Nox2B and Nox4, which caused oxidative stress. In addition, these nanoparticles demonstrated an upregulation in the expression of the antioxidant genes Gclc and Nqo-1 in a dose-dependent manner. Conclusion: The study indicates the promising potential of rutin-loaded LCNs as an effective treatment strategy in patients with high oxidant loads in various respiratory diseases.
- ItemTargeting eosinophils in respiratory diseases: biological axis, emerging therapeutics and treatment modalities(2021) Lee, L.-Y.; Hew, G.S.Y.; Mehta, M.; Shukla, S.D.; Satija, S.; Khurana, N.; Anand, K.; Dureja, H.; Singh, S.K.; Mishra, V.; Singh, P.K.; Gulati, M.; Prasher, P.; Aljabali, A.A.A.; Tambuwala, M.M.; Thangavelu, L.; Panneerselvam, J.; Gupta, G.; Zacconi, Flavia C. M.; Shastri, M.; Jha, N.K.; Xenaki, D.; MacLoughlin, R.; Oliver, B.G.; Chellappan, D.K.; Dua, K.Eosinophils are bi-lobed, multi-functional innate immune cells with diverse cell surface receptors that regulate local immune and inflammatory responses. Several inflammatory and infectious diseases are triggered with their build up in the blood and tissues. The mobilization of eosinophils into the lungs is regulated by a cascade of processes guided by Th2 cytokine generating T-cells. Recruitment of eosinophils essentially leads to a characteristic immune response followed by airway hyperresponsiveness and remodeling, which are hallmarks of chronic respiratory diseases. By analysing the dynamic interactions of eosinophils with their extracellular environment, which also involve signaling molecules and tissues, various therapies have been invented and developed to target respiratory diseases. Having entered clinical testing, several eosinophil targeting therapeutic agents have shown much promise and have further bridged the gap between theory and practice. Moreover, researchers now have a clearer understanding of the roles and mechanisms of eosinophils. These factors have successfully assisted molecular biologists to block specific pathways in the growth, migration and activation of eosinophils. The primary purpose of this review is to provide an overview of the eosinophil biology with a special emphasis on potential pharmacotherapeutic targets. The review also summarizes promising eosinophil-targeting agents, along with their mechanisms and rationale for use, including those in developmental pipeline, in clinical trials, or approved for other respiratory disorders.