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Browsing by Author "Dua, Kamal"

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Advances in nanotechnology-based drug delivery in targeting PI3K signaling in respiratory diseases
(FUTURE MEDICINE LTD, 2021) Chan, Yinghan; MacLoughlin, Ronan; Zacconi, Flavia C. M.; Tambuwala, Murtaza M.; Pabari, Ritesh M.; Singh, Sachin Kumar; Pinto Andreoli, Terezinha de Jesus; Gupta, Gaurav; Chellappan, Dinesh Kumar; Dua, Kamal
Albumin Nano-Encapsulation of Piceatannol Enhances Its Anticancer Potential in Colon Cancer Via Downregulation of Nuclear p65 and HIF-1α
(2020) Aljabali, Alaa A. A.; Bakshi, Hamid A.; Hakkim, Faruck L.; Haggag, Yusuf A.; Al-Batanyeh, Khalid M.; Al Zoubi, Mazhar S.; Al-Trad, Bahaa; Nasef, Mohamed M.; Satija, Saurabh; Mehta, Meenu; Pabreja, Kavita; Mishra, Vijay; Khan, Mohammed; Abobaker, Salem; Azzouz, Ibrahim M.; Dureja, Harish; Pabari, Ritesh M.; Dardouri, Ashref Ali K.; Kesharwani, Prashant; Gupta, Gaurav; Shukla, Shakti Dhar; Prasher, Parteek; Charbe, Nitin B.; Negi, Poonam; Kapoor, Deepak N.; Chellappan, Dinesh Kumar; da Silva, Mateus Webba; Thompson, Paul; Dua, Kamal; McCarron, Paul; Tambuwala, Murtaza M.
Piceatannol (PIC) is known to have anticancer activity, which has been attributed to its ability to block the proliferation of cancer cells via suppression of the NF-kB signaling pathway. However, its effect on hypoxia-inducible factor (HIF) is not well known in cancer. In this study, PIC was loaded into bovine serum albumin (BSA) by desolvation method as PIC-BSA nanoparticles (NPs). These PIC-BSA nanoparticles were assessed for in vitro cytotoxicity, migration, invasion, and colony formation studies and levels of p65 and HIF-1 alpha. Our results indicate that PIC-BSA NPs were more effective in downregulating the expression of nuclear p65 and HIF-1 alpha in colon cancer cells as compared to free PIC. We also observed a significant reduction in inflammation induced by chemical colitis in mice by PIC-BSA NPs. Furthermore, a significant reduction in tumor size and number of colon tumors was also observed in the murine model of colitis-associated colorectal cancer, when treated with PIC-BSA NPs as compared to free PIC. The overall results indicate that PIC, when formulated as PIC-BSA NPs, enhances its therapeutic potential. Our work could prompt further research in using natural anticancer agents as nanoparticels with possible human clinical trails. This could lead to the development of a new line of safe and effective therapeutics for cancer patients.
An overview of vaccine development for COVID-19
(2021) Shahcheraghi, Seyed H.; Ayatollahi, Jamshid; Aljabali, Alaa A. A.; Shastri, Madhur D.; Shukla, Shakti D.; Chellappan, Dinesh K.; Jha, Niraj K.; Anand, Krishnan; Katari, Naresh K.; Mehta, Meenu; Satija, Saurabh; Dureja, Harish; Mishra, Vijay; Almutary, Abdulmajeed G.; Alnuqaydan, Abdullah M.; Charbe, Nitin; Prasher, Parteek; Gupta, Gaurav; Dua, Kamal; Lotfi, Marzieh; Bakshi, Hamid A.; Tambuwala, Murtaza M.
The COVID-19 pandemic continues to endanger world health and the economy. The causative SARS-CoV-2 coronavirus has a unique replication system. The end point of the COVID-19 pandemic is either herd immunity or widespread availability of an effective vaccine. Multiple candidate vaccines - peptide, virus-like particle, viral vectors (replicating and nonreplicating), nucleic acids (DNA or RNA), live attenuated virus, recombinant designed proteins and inactivated virus - are presently under various stages of expansion, and a small number of vaccine candidates have progressed into clinical phases. At the time of writing, three major pharmaceutical companies, namely Pfizer and Moderna, have their vaccines under mass production and administered to the public. This review aims to investigate the most critical vaccines developed for COVID-19 to date.
Anti-bacterial activity of inorganic nanomaterials and their antimicrobial peptide conjugates against resistant and non-resistant pathogens
(2020) Pardhi, Dinesh M.; Karaman, Didem Sen; Timonen, Juri; Wu, Wei; Zhang, Qi; Satija, Saurabh; Mehta, Meenu; Charbe, Nitin; McCarron, Paul A.; Tambuwala, Murtaza M.; Bakshi, Hamid A.; Negi, Poonam; Aljabali, Alaa A.; Dua, Kamal; Chellappan, Dinesh K.; Behera, Ajit; Pathak, Kamla; Watharkar, Ritesh B.; Rautio, Jarkko; Rosenholm, Jessica M.
This review details the antimicrobial applications of inorganic nanomaterials of mostly metallic form, and the augmentation of activity by surface conjugation of peptide ligands. The review is subdivided into three main sections, of which the first describes the antimicrobial activity of inorganic nanomaterials against gram-positive, gram-negative and multidrug-resistant bacterial strains. The second section highlights the range of antimicrobial peptides and the drug resistance strategies employed by bacterial species to counter lethality. The final part discusses the role of antimicrobial peptide-decorated inorganic nanomaterials in the fight against bacterial strains that show resistance. General strategies for the preparation of antimicrobial peptides and their conjugation to nanomaterials are discussed, emphasizing the use of elemental and metallic oxide nanomaterials. Importantly, the permeation of antimicrobial peptides through the bacterial membrane is shown to aid the delivery of nanomaterials into bacterial cells. By judicious use of targeting ligands, the nanomaterial becomes able to differentiate between bacterial and mammalian cells and, thus, reduce side effects. Moreover, peptide conjugation to the surface of a nanomaterial will alter surface chemistry in ways that lead to reduction in toxicity and improvements in biocompatibility.
Bio-click chemistry: a bridge between biocatalysis and click chemistry
(2022) Rodríguez Sánchez, Diego Fernando; Moglie, Yanina; Ramírez Sarmiento, César Antonio; Singh, Sachin Kumar; Dua, Kamal; Zacconi, Flavia C. M.
The fields of click chemistry and biocatalysis have rapidly grown over the last two decades. The development of robust and active biocatalysts and the widespread use of straightforward click reactions led to significant interactions between these two fields. Therefore the name bio-click chemistry seems to be an accurate definition of chemoenzymatic reactions cooperating with click transformations. Bio-click chemistry can be understood as the approach towards molecules of high-value using a green and sustainable approach by exploiting the potential of biocatalytic enzyme activity combined with the reliable nature of click reactions. This review summarizes the principal bio-click chemistry reactions reported over the last two decades, with a special emphasis on small molecules. Contributions to the field of bio-click chemistry are manifold, but the synthesis of chiral molecules with applications in medicinal chemistry and sustainable syntheses will be especially highlighted.
Biomedical Applications of polymeric micelles in the treatment of diabetes mellitus: Current success and future approaches
(2022) Kaur, Jaskiran; Gulati, Monica; Zacconi, Flavia C. M.; Dureja, Harish; Loebenberg, Raimar; Ansari, Md Salahuddin; AlOmeir, Othman; Alam, Aftab; Chellappan, Dinesh Kumar; Gupta, Gaurav; Jha, Niraj Kumar; Pinto, Terezinha de Jesus Andreoli; Morris, Andrew; Choonara, Yahya E.; Adams, Jon; Dua, Kamal; Singh, Sachin Kumar
Introduction Diabetes mellitus (DM) is the most common metabolic disease and multifactorial, harming patients worldwide. Extensive research has been carried out in the search for novel drug delivery systems offering reliable control of glucose levels for diabetics, aiming at efficient management of DM. Areas covered Polymeric micelles (PMs) as smart drug delivery nanocarriers are discussed, focusing on oral drug delivery applications for the management of hyperglycemia. The most recent approaches used for the preparation of smart PMs employ molecular features of amphiphilic block copolymers (ABCs), such as stimulus sensitivity, ligand conjugation, and as a more specific example the ability to inhibit islet amyloidosis. Expert opinion PMs provide a unique platform for self-regulated or spatiotemporal drug delivery, mimicking the working mode of pancreatic islets to maintain glucose homeostasis for prolonged periods. This unique characteristic is achieved by tailoring the functional chemistry of ABCs considering the physicochemical traits of PMs, including sensing capabilities, hydrophobicity, etc. In addition, the application of ABCs for the inhibition of conformational changes in islet amyloid polypeptide garnered attention as one of the root causes of DM. However, research in this field is limited and further studies at the clinical level are required.
Development of mushroom polysaccharide and probiotics based solid self-nanoemulsifying drug delivery system loaded with curcumin and quercetin to improve their dissolution rate and permeability: State of the art
(ELSEVIER, 2021) Khursheed, Rubiya; Singh, Sachin Kumar; Wadhwa, Sheetu; Gulati, Monica; Kapoor, Bhupinder; Jain, Subheet Kumar; Gowthamarajan, Kuppusamy; Zacconi, Flavia C. M.; Chellappan, Dinesh Kumar; Gupta, Gaurav; Jha, Niraj Kumar; Gupta, Piyush Kumar; Dua, Kamal
The role of mushroom polysaccharides and probiotics as pharmaceutical excipients for development of nano-carriers has never been explored. In the present study an attempt has been made to explore Ganoderma lucidum extract powder (GLEP) containing polysaccharides and probiotics to convert liquid self nanoemulsifying drug delivery system (SNEDDS) into solid free flowing powder. Two lipophilic drugs, curcumin and quercetin were used in this study due to their dissolution rate limited oral bioavailability and poor permeability. These were loaded into liquid SNEDDS by dissolving them into isotropic mixture of Labrafill M1944CS, Capmul MCM, Tween-80 and Transcutol P. The liquid SNEDDS were solidified using probiotics and mushroom polysaccharides as carriers and Aerosil-200 as coating agent. The solidification was carried out using spray drying process. The process and formulation variables for spray drying process of liquid SNEDDS were optimized using Box Behnken Design to attain required powder properties. The release of both drugs from the optimized spray dried (SD) formulation was found to be more than 90%, whereas, it was less than 20% for unprocessed drugs. The results of DSC, PXRD and SEM, showed that the developed L-SNEDDS preconcentrate was successfully loaded onto the porous surface of probiotics, mushroom polysaccharides and Aerosil-200.
Dietary Crocin is Protective in Pancreatic Cancer while Reducing Radiation-Induced Hepatic Oxidative Damage
(2020) Bakshi, Hamid A.; Al Zoubi, Mazhar S.; Faruck, Hakkim L.; Aljabali, Alaa A. A.; Rabi, Firas A.; Hafiz, Amin A.; Al-Batanyeh, Khalid M.; Al-Trad, Bahaa; Ansari, Prawej; Nasef, Mohamed M.; Charbe, Nitin B.; Satija, Saurabh; Mehta, Meenu; Mishra, Vijay; Gupta, Gaurav; Abobaker, Salem; Negi, Poonam; Azzouz, Ibrahim M.; Dardouri, Ashref Ali K.; Dureja, Harish; Prasher, Parteek; Chellappan, Dinesh K.; Dua, Kamal; Da Silva, Mateus Webba; El Tanani, Mohamed; McCarron, Paul A.; Tambuwala, Murtaza M.
Pancreatic cancer is one of the fatal causes of global cancer-related deaths. Although surgery and chemotherapy are standard treatment options, post-treatment outcomes often end in a poor prognosis. In the present study, we investigated anti-pancreatic cancer and amelioration of radiation-induced oxidative damage by crocin. Crocin is a carotenoid isolated from the dietary herb saffron, a prospect for novel leads as an anti-cancer agent. Crocin significantly reduced cell viability of BXPC3 and Capan-2 by triggering caspase signaling via the downregulation of Bcl-2. It modulated the expression of cell cycle signaling proteins P53, P21, P27, CDK2, c-MYC, Cyt-c and P38. Concomitantly, crocin treatment-induced apoptosis by inducing the release of cytochrome c from mitochondria to cytosol. Microarray analysis of the expression signature of genes induced by crocin showed a substantial number of genes involved in cell signaling pathways and checkpoints (723) are significantly affected by crocin. In mice bearing pancreatic tumors, crocin significantly reduced tumor burden without a change in body weight. Additionally, it showed significant protection against radiation-induced hepatic oxidative damage, reduced the levels of hepatic toxicity and preserved liver morphology. These findings indicate that crocin has a potential role in the treatment, prevention and management of pancreatic cancer.
Dynamics of Prolyl Hydroxylases Levels During Disease Progression in Experimental Colitis
(2019) Bakshi, Hamid A.; Mishra, Vijay; Satija, Saurabh; Mehta, Meenu; Hakkim, Faruk L.; Kesharwani, Prashant; Dua, Kamal; Chellappan, Dinesh K.; Charbe, Nitin B.; Shrivastava, Garima; Rajeshkumar, S.; Aljabali, Alaa A.; Al-Trad, Bahaa; Pabreja, Kavita; Tambuwala, Murtaza M.
Hypoxia inducible factor (HIF)-prolyl hydroxylase (PHD) inhibitors are shown to be protective in several models of inflammatory bowel disease (IBD). However, these non-selective inhibitors are known to inhibit all the three isoforms of PHD, i.e. PHD-1, PHD-2 and PHD-3. In the present report, we investigated the associated changes in levels of PHDs during the development and recovery of chemically induced colitis in mice. The results indicated that in the experimental model of murine colitis, levels of both, PHD-1 and PHD-2 were found to be increased with the progression of the disease; however, the level of PHD-3 remained the same in group of healthy controls and mice with colitis. Thus, the findings advocated that inhibitors, which inhibited all three isoforms of PHD could not be ideal therapeutics for IBD since PHD-3 is required for normal gut function. Hence, this necessitates the development of new compounds capable of selectively inhibiting PHD-1 and PHD-2 for effective treatment of IBD.
Green by Design: Convergent Synthesis, Computational Analyses, and Activity Evaluation of New FXa Inhibitors Bearing Peptide Triazole Linking Units
(2022) Rodriguez, Diego F.; Duran Osorio, Francisca; Duarte, Yorley; Olivares, Pedro; Moglie, Yanina; Dua, Kamal; Zacconi, Flavia C. M.
Green chemistry implementation has led to promising results in waste reduction in the pharmaceutical industry. However, the early sustainable development of pharmaceutically active compounds and ingredients remains a considerable challenge. Herein, we wish to report a green synthesis of new pharmaceutically active peptide triazoles as potent factor Xa inhibitors, an important drug target associated with the treatment of diverse cardiovascular diseases. The new inhibitors were synthesized in three steps, featuring cycloaddition reactions (high atom economy), microwave-assisted organic synthesis (energy efficiency), and copper nanoparticle catalysis, thus featuring Earth-abundant metals. The molecules obtained showed FXa inhibition, with IC50-values as low as 17.2 mu M and no associated cytotoxicity in HEK293 and HeLa cells. These results showcase the environmental potential and chemical implications of the applied methodologies for the development of new molecules with pharmacological potential.
Hypoxia-Inducible Factor (HIF): Fuel for Cancer Progression
(Bentham Science Publ. LTD, 2021) Satija, Saurabh; Kaur, Harpreet; Tambuwala, Murtaza M.; Sharma, Prabal; Vyas, Manish; Khurana, Navneet; Sharma, Neha; Bakshi, Hamid A.; Charbe, Nitin B.; Zacconi, Flavia C. M.; Aljabali, Alaa A.; Nammi, Srinivas; Dureja, Harish; Singh, Thakur G.; Gupta, Gaurav; Dhanjal, Daljeet S.; Dua, Kamal; Chellappan, Dinesh K.; Mehta, Meenu
Hypoxia is an integral part of the tumor microenvironment, caused primarily due to rapidly multiplying tumor cells and a lack of proper blood supply. Among the major hypoxic pathways, HIF-1 transcription factor activation is one of the widely investigated pathways in the hypoxic tumor microenvironment (TME). HIF-1 is known to activate several adaptive reactions in response to oxygen deficiency in tumor cells. HIF-1 has two subunits, HIF-1 beta (constitutive) and HIF-1 alpha (inducible). The HIF-1 alpha expression is largely regulated via various cytokines (through PI3K-ACT-mTOR signals), which involves the cascading of several growth factors and oncogenic cascades. These events lead to the loss of cellular tumor suppressant activity through changes in the level of oxygen via oxygen-dependent and oxygen-independent pathways. The significant and crucial role of HIF in cancer progression and its underlying mechanisms have gained much attention lately among the translational researchers in the fields of cancer and biological sciences, which have enabled them to correlate these mechanisms with various other disease modalities. In the present review, we have summarized the key findings related to the role of HIF in the progression of tumors.
Luteolin: a favonoid with a multifaceted anticancer potential
(2022) Prasher, Parteek; Sharma, Mousmee; Singh, Sachin K.; Gulati, Monica; Chellappan, Dinesh K.; Zacconi, Flavia C. M.; De Rubis, Gabriele; Gupta, Gaurav; Sharifi-Rad, Javad; Cho, William C.; Dua, Kamal
Therapeutic effect of phytochemicals has been emphasized in the traditional medicine owing to the presence of bioactive molecules, such as polyphenols. Luteolin is a flavone belonging to the flavonoid class of polyphenolic phytochemicals with healing effect on hypertension, inflammatory disorders, and cancer due to its action as pro-oxidants and antioxidants. The anticancer profile of luteolin is of interest due to the toxic effect of contemporary chemotherapy paradigm, leading to the pressing need for the development and identification of physiologically benevolent anticancer agents and molecules. Luteolin exerts anticancer activity by downregulation of key regulatory pathways associated with oncogenesis, in addition to the induction of oxidative stress, cell cycle arrest, upregulation of apoptotic genes, and inhibition of cell proliferation and angiogenesis in cancer cells. In this review, we discuss about the anticancer profile of luteolin.
Perfluorocarbons Therapeutics in Modern Cancer Nanotechnology for Hypoxia-induced Anti-tumor Therapy
(2021) Satija, Saurabh; Sharma, Prabal; Kaur, Harpreet; Dhanjal, Daljeet S.; Chopra, Reena S.; Khurana, Navneet; Vyas, Manish; Sharma, Neha; Tambuwala, Murtaza M.; Bakshi, Hamid A.; Charbe, Nitin B.; Zacconi, Flavia C. M.; Chellappan, Dinesh K.; Dua, Kamal; Mehta, Meenu
With an estimated failure rate of about 90%, immunotherapies that are intended for the treatment of solid tumors have caused an anomalous rise in the mortality rate over the past decades. It is apparent that resistance towards such therapies primarily occurs due to elevated levels of HIF-1 (Hypoxia-induced factor) in tumor cells, which are caused by disrupted microcirculation and diffusion mechanisms. With the advent of nanotechnology, several innovative advances were brought to the fore; and, one such promising direction is the use of perfluorocarbon nanoparticles in the management of solid tumors. Perfluorocarbon nanoparticles enhance the response of hypoxia-based agents (HBAs) within the tumor cells and have been found to augment the entry of HBAs into the tumor micro-environment. The heightened penetration of HBAs causes chronic hypoxia, thus aiding in the process of cell quiescence. In addition, this technology has also been applied in photodynamic therapy, where oxygen self-enriched photosensitizers loaded perfluorocarbon nanoparticles are employed. The resulting processes initiate a cascade, depleting tumour oxygen and turning it into a reactive oxygen species eventually to destroy the tumour cell. This review elaborates on the multiple applications of nanotechnology based perfluorocarbon formulations that are being currently employed in the treatment of tumour hypoxia.
Probing 3CL protease: Rationally designed chemical moieties for COVID-19
(2020) Sharma, Mousmee; Prasher, Parteek; Mehta, Meenu; Zacconi, Flavia C.; Singh, Yogendra; Kapoor, Deepak N.; Dureja, Harish; Pardhi, Dinesh M.; Tambuwala, Murtaza M.; Gupta, Gaurav; Chellappan, Dinesh K.; Dua, Kamal; Satija, Saurabh
Protein and peptide delivery to lungs by using advanced targeted drug delivery
(2022) Chellappan, Dinesh Kumar; Prasher, Parteek; Saravanan, Vilashini; Yee, Vanessa See Vern; Chi, Wendy Chai Wen; Wong, Jia Wei; Wong, Joon Kang; Wong, Jing Tong; Wan, Wai; Chellian, Jestin; Molugulu, Nagashekhara; Prabu, Sakthivel Lakshmana; Ibrahim, Rania; Darmarajan, Thiviya; Candasamy, Mayuren; Singh, Pankaj Kumar; Mishra, Vijay; Shastri, Madhur D.; Zacconi, Flavia C. M.; Chakraborty, Amlan; Mehta, Meenu; Gupta, Piyush Kumar; Dureja, Harish; Gulati, Monica; Singh, Sachin Kumar; Gupta, Gaurav; Jha, Niraj Kumar; Oliver, Brian Gregory George; Dua, Kamal
The challenges and difficulties associated with conventional drug delivery systems have led to the emergence of novel, advanced targeted drug delivery systems. Therapeutic drug delivery of proteins and peptides to the lungs is complicated owing to the large size and polar characteristics of the latter. Nevertheless, the pulmonary route has attracted great interest today among formulation scientists, as it has evolved into one of the important targeted drug delivery platforms for the delivery of peptides, and related compounds effectively to the lungs, primarily for the management and treatment of chronic lung diseases. In this review, we have discussed and summarized the current scenario and recent developments in targeted delivery of proteins and peptide-based drugs to the lungs. Moreover, we have also highlighted the advantages of pulmonary drug delivery over conventional drug delivery approaches for peptide-based drugs, in terms of efficacy, retention time and other important pharmacokinetic parameters. The review also highlights the future perspectives and the impact of targeted drug delivery on peptide-based drugs in the coming decade.
Self-nanoemulsifying composition containing curcumin, quercetin, Ganoderma lucidum extract powder and probiotics for effective treatment of type 2 diabetes mellitus in streptozotocin induced rats
(Elsevier B.V., 2022) Khursheed, Rubiya; Singh, Sachin Kumar; Kumar, Bimlesh; Wadhwa, Sheetu; Gulati, Mónica; Anupriya, A.; Awasthi, Ankit; Vishwas, Sukriti; Kaur, Jaskiran; Corrie, Leander; Arya, K. R.; Kumar, Rajan; Jha, Niraj Kumar; Gupta, Piyush Kumar; Zacconi, Flavia C. M.; Dua, Kamal; Chitranshi, Nitin; Mustafa, Gulam; Kumar, Ankit
Liquid self-nanoemulsifying drug delivery system (L-SNEDDS) of curcumin and quercetin were prepared by dissolving them in isotropic mixture of Labrafil M1944CS®, Capmul MCM®, Tween-80® and Transcutol P®. The prepared L-SNEDDS were solidified using Ganoderma lucidum extract, probiotics and Aerosil-200® using spray drying. These were further converted into pellets using extrusion-spheronization. The mean droplet size and zeta potential of L-SNEDDS were found to be 63.46 ± 2.12 nm and − 14.8 ± 3.11 mV while for solid SNEDDS pellets, these were 72.46 ± 2.16 nm and −38.7 ± 1.34 mV, respectively. The dissolution rate for curcumin and quercetin each was enhanced by 4.5 folds while permeability was enhanced by 5.28 folds (curcumin) and 3.35 folds (quercetin) when loaded into SNEDDS pellets. The Cmax for curcumin and quercetin containing SNEDDS pellets was found 532.34 ± 5.64 ng/mL and 4280 ± 65.67 ng/mL, respectively. This was 17.55 and 3.48 folds higher as compared to their naïve forms. About 50.23– and 5.57-folds increase in bioavailability was observed for curcumin and quercetin respectively, upon loading into SNEDDS pellets. SNEDDS pellets were found stable at accelerated storage conditions. The developed formulation was able to normalize the levels of blood glucose, lipids, antioxidant biomarkers, and tissue architecture of pancreas and liver in streptozotocin induced diabetic rats as compared to their naïve forms.
Small interfering RNA for cancer treatment: overcoming hurdles in delivery
(2020) Zacconi, Flavia C. M.; Aljabali, Alaa A.A.; Chellappan, D.K.; Shrivastava, Garima; Gupta, Gaurav; Bakshi, Hamid A.; Dua, Kamal; Metha, Meenu; Tambuwala, Murtaza M.; Amnerkar, Nikhil D.; Charbe, Nitin Bharat; Negi, Poonam; Satheeshkumar, Rajendran; Khadse, Saurabh C.; Satija, Saurabh
In many ways, cancer cells are different from healthy cells. A lot of tactical nano-based drug delivery systems are based on the difference between cancer and healthy cells. Currently, nanotechnology-based delivery systems are the most promising tool to deliver DNA-based products to cancer cells. This review aims to highlight the latest development in the lipids and polymeric nanocarrier for siRNA delivery to the cancer cells. It also provides the necessary information about siRNA development and its mechanism of action. Overall, this review gives us a clear picture of lipid and polymer-based drug delivery systems, which in the future could form the base to translate the basic siRNA biology into siRNA-based cancer therapies. (C) 2020 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.
Synthesis and Anticancer Properties of 'azole' based Chemotherapeutics as Emerging Chemical Moieties: A Comprehensive Review
(2020) Prasher, P.; Sharma, M.; Zacconi, Flavia C. M.; Gupta, G.; Ajabali, Alaa A. A.; Mishra, V.; Tambuwala, M. M.; Kapoor, D. N.; Negi, P.; Andreoli Pinto, Terezinha de Jesús; Singh, I.; Chellappan, D.; Dua, Kamal
Azole frameworks serve as privileged scaffolds in the contemporary drug design paradigm owing to their unique physicochemical profile that promotes the development of highly selective, physiological benevolent chemotherapeutics. Several azole nuclei function as bioisostere in medicinal chemistry and prompt the development of tailored therapeutics for targeting the desired biological entities. Besides, the azole scaffold forms an integral part in the advanced drug designing methodologies, such as target template insitu drug synthesis, that assists in rapid identification of the hit molecules form a diverse pool of leads; and direct biomolecule-drug conjugation, along with bioorthogonal strategies that ensure localization, and superior target specificity of the directed therapeutic. Lastly, the structural diversity of azole framework and high yielding click synthetic methods provide a comprehensive Structure-Activity Relationship analysis for design optimization of the potential drug molecules by fine-tuning the placement of different substituents critical for the activity. This review provides a comprehensive analysis of the synthesis and anticancer potential of azole based chemotherapeutics.
Targeting LIN28: a new hope in prostate cancer theranostics
(2021) Shrivastava, Garima; Aljabali, Alaa A. A.; Shahcheraghi, Seyed Hossein; Lotfi, Marzieh; Shastri, Madhur D.; Shukla, Shakti D.; Chellappan, Dinesh K.; Jha, Niraj Kumar; Anand, Krishnan; Dureja, Harish; Pabari, Ritesh M.; Mishra, Vijay; Almutary, Abdulmajeed G.; Alnuqaydan, Abdullah M.; Charbe, Nitin; Prasher, Parteek; Negi, Poonam; Goyal, Rohit; Dua, Kamal; Gupta, Gaurav; Serrano-Aroca, Angel; Bahar, Bojlul; Barh, Debmalya; Panda, Pritam Kumar; Takayama, Kazuo; Lundstorm, Kenneth; McCarron, Paul; Bakshi, Hamid; Tambuwala, Murtaza M.
The mortality and morbidity rates for prostate cancer have recently increased to alarming levels, rising higher than lung cancer. Due to a lack of drug targets and molecular probes, existing theranostic techniques are limited. Human LIN28A and its paralog LIN28B overexpression are associated with a number of tumors resulting in a remarkable increase in cancer aggression and poor prognoses. The current review aims to highlight recent work identifying the key roles of LIN28A and LIN28B in prostate cancer, and to instigate further preclinical and clinical research in this important area.
Targeting mucus barrier in respiratory diseases by chemically modified advanced delivery systems
(ELSEVIER IRELAND LTD, 2022) Prasher, Parteek; Sharma, Mousmee; Singh, Sachin Kumar; Gulati, Monica; Jha, Niraj Kumar; Gupta, Piyush Kumar; Gupta, Gaurav; Chellappan, Dinesh Kumar; Zacconi, Flavia C. M.; Pinto, Terezinha de Jesus Andreoli; Chan, Yinghan; Liu, Gang; Paudel, Keshav Raj; Hansbro, Philip M.; Oliver, Brian Gregory George; Dua, Kamal
Mucus gel constitutes of heavily cross-linked mucin fibers forming a viscoelastic, dense porous network that coats all the exposed epithelia not covered with the skin. The layer provides protection to the underlying gastrointestinal, respiratory, and female reproductive tracts, in addition to the organs such as the surface of eye by trapping the pathogens, irritants, environmental fine particles, and potentially hazardous foreign matter. However, this property of mucus gel poses a substantial challenge for realizing the localized and sustained drug delivery across the mucosal surfaces. The mucus permeating particles that spare the protective properties of mucus gel improve the therapeutic potency of the drugs aimed at the management of diseases, including sexually transmitted infections, lung cancer, irritable bowel disease, degenerative eye diseases and infections, and cystic fibrosis. As such, the mucoadhesive materials conjugated with drug molecules display a prolonged retention time in the mucosal gel that imparts a sustained release of the deliberated drug molecules across the mucosa. The contemporarily developed mucus penetrating materials for drug delivery applications comprise of a finer size, appreciable hydrophilicity, and a neutral surface to escape the entrapment within the cross-inked mucus fibers. Pertaining to the mucus secretion as a first line of defence in respiratory tract in response to the invading physical, chemical, and biological pathogens, the development of mucus penetrating materials hold promise as a stalwart approach for revolutionizing the respiratory drug delivery paradigm. The present review provides an epigrammatic collation of the mucus penetrating/mucoadhesive materials for achieving a controlled/sustained release of the cargo pharmaceutics and drug molecules across the respiratory mucus barrier.

Browsing by Author "Dua, Kamal"

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