Advances in nanomedicine have become indispensable for targeted drug delivery, early detection, and increasingly personalized approaches to cancer treatment. Nanoparticle-based drug-delivery systems have overcome some of the limitations associated with traditional cancer-therapy administration, such as reduced drug solubility, chemoresistance, systemic toxicity, narrow therapeutic indices, and poor oral bioavailability. Advances in the field of nanomedicine include "smart" drug delivery, or multiple levels of targeting, and extended-release drug-delivery systems that provide additional methods of overcoming these limitations. More recently, the idea of combining smart drug delivery with extended-release has emerged in hopes of developing highly efficient nanoparticles with improved delivery, bioavailability, and safety profiles. Although functionalized and extended-release drug-delivery systems have been studied extensively, there remain gaps in the literature concerning their application in cancer treatment. We aim to provide an overview of smart and extended-release drug-delivery systems for the delivery of cancer therapies, as well as to introduce innovative advancements in nanoparticle design incorporating these principles. With the growing need for increasingly personalized medicine in cancer treatment, smart extended-release nanoparticles have the potential to enhance chemotherapy delivery, patient adherence, and treatment outcomes in cancer patients.

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Recent advances in "smart" delivery systems for extended drug release in cancer therapy.

COVID-19 is a viral disease caused by a new severe acute respiratory syndrome (SARS-CoV-2), which has quickly resulted in a pandemic. As a great threat to global public health, the development of a treatment has become vital, and a rush to find a cure has mobilized researchers from all areas across the world. Synthetic drugs, such as hydroxychloroquine, have gained attention. However, the efficacy of repositioned drugs is still under evaluation, and besides, some severe side effects are a cause for concern. This emphasizes the urgency for treatment options, which can be both safe and effective. With this in mind, natural products could be an important resource in the development of COVID-19 treatment, as they have already contributed in the past to treatments against other viruses, such as HIV, MERS-CoV, and influenza. Natural products are described long term as bioactive substances and some phytochemical classes such as flavonoids, alkaloids, and peptides are known antiviral bioproducts, and have been virtually tested with success against COVID-19. However, important issues still need to be addressed as to their bioavailability and true efficacy in vivo. This review intends to systematically evaluate the natural metabolites that could potentially be used against this new disease looking at their natural sources, mechanism of action and previous pharmacological usages. The aim is to provide a starting point for this research area in order to speed up the establishment of anti-SARS-CoV-2 bioproducts.

/pdf/natural-products-role-against-covid-19-ab1s80hnze.pdf

Natural products' role against COVID-19

COVID-19, a disease induced by SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2), has been the cause of a worldwide pandemic. Though extensive research works have been reported in recent days on the development of effective therapeutics against this global health crisis, there is still no approved therapy against SARS-CoV-2. In the present study, plant-synthesized secondary metabolites (PSMs) have been prioritized to make a review focusing on the efficacy of plant-originated therapeutics for the treatment of COVID-19. Plant metabolites are a source of countless medicinal compounds, while the diversity of multidimensional chemical structures has made them superior to treat serious diseases. Some have already been reported as promising alternative medicines and lead compounds for drug repurposing and discovery. The versatility of secondary metabolites may provide novel antibiotics to tackle MDR (Multi-Drug Resistant) microbes too. This review attempted to find out plant metabolites that have the therapeutic potential to treat a wide range of viral pathogens. The study includes the search of remedies belonging to plant families, susceptible viral candidates, antiviral assays, and the mode of therapeutic action; this attempt resulted in the collection of an enormous number of natural therapeutics that might be suggested for the treatment of COVID-19. About 219 plants from 83 families were found to have antiviral activity. Among them, 149 plants from 71 families were screened for the identification of the major plant secondary metabolites (PSMs) that might be effective for this pandemic. Our investigation revealed that the proposed plant metabolites can serve as potential anti- SARS-CoV-2 lead molecules for further optimization and drug development processes to combat COVID-19 and future pandemics caused by viruses. This review will stimulate further analysis by the scientific community and boost antiviral plant-based research followed by novel drug designing.

Plants Metabolites: Possibility of Natural Therapeutics Against the COVID-19 Pandemic

The novel coronavirus SARS-CoV-2 disease "COVID-19" emerged in China and rapidly spread to other countries; due to its rapid worldwide spread, the WHO has declared this as a global emergency. As there is no specific treatment prescribed to treat COVID-19, the seeking of suitable therapeutics among existing drugs seems valuable. The structure availability of coronavirus macromolecules has encouraged the finding of conceivable anti-SARS-CoV-2 therapeutics through in silico analysis. The results reveal that quinoline,1,2,3,4-tetrahydro-1-[(2-phenylcyclopropyl)sulfonyl]-trans-(8CI) and saquinavir strongly interact with the active site (Cys-His catalytic dyad), thereby are predicted to hinder the activity of SARS-CoV-2 3CLpro. Out of 113 quinoline-drugs, elvitegravir and oxolinic acid are able to interact with the NTP entry-channel and thus interfere with the RNA-directed 5'-3' polymerase activity of SARS-CoV-2 RdRp. The bioactivity-prediction results also validate the outcome of the docking study. Moreover, as SARS-CoV-2 Spike-glycoprotein uses human ACE2-receptor for viral entry, targeting the Spike-RBD-ACE2 has been viewed as a promising strategy to control the infection. The result shows rilapladib is the only quinoline that can interrupt the Spike-RBD-ACE2 complex. In conclusion, owing to their ability to target functional macromolecules of SARS-CoV-2, along with positive ADMET properties, quinoline,1,2,3,4-tetrahydro-1-[(2-phenylcyclopropyl)sulfonyl]-trans-(8CI), saquinavir, elvitegravir, oxolinic acid, and rilapladib are suggested for the treatment of COVID-19.

Quinolines-Based SARS-CoV-2 3CLpro and RdRp Inhibitors and Spike-RBD-ACE2 Inhibitor for Drug-Repurposing Against COVID-19: An in silico Analysis

Protease targeted COVID-19 drug discovery and its challenges: Insight into viral main protease (Mpro) and papain-like protease (PLpro) inhibitors.

OBJECTIVE: Currently, Coronavirus COVID-19 is spreading worldwide very rapidly and its control is very difficult because there is no effective vaccine or drugs available in markets. This virus can infect both animals and people and cause illnesses of the respiratory tract. WHO has declared Coronavirus as pandemic and the whole world is fighting against Coronavirus. Globally, more than 199,478 people have been diagnosed with COVID-19. As of March 18, 2020, more than 167 countries have been affected and more than 8000 deaths have been reported. The main country being affected is China followed by Italy, Iran, Spain, France, and the USA. MATERIALS AND METHODS: Since there are no effective drugs available against Coronavirus, we conducted virtual screening of phytochemicals to find novel compounds against this virus. Hence, we created a phytochemical library of 318 phytochemicals from 11 plants which have been reported as antiviral, antibacterial and antifungal activity. The phytochemical library was subjected to virtual screening against molecular targets; Main protease (Mpro) and Angiotensin-Converting Enzyme 2 (ACE2). RESULTS: Top 10 compounds were selected from each target which had better and significantly low binding energy as compared to the reference molecule. CONCLUSIONS: Based on the binding energy score, we suggest that these compounds can be tested against Coronavirus and used to develop effective antiviral drugs.

In silico screening of natural compounds against COVID-19 by targeting Mpro and ACE2 using molecular docking.

There is a continuously growing interest in the pharmaceutical industry for extended release oral drug delivery systems. There is also high interest for design of dosage formulations that allow high drug loading, particularly for actives with high water solubility. Conventional drug delivery systems are known to provide a prompt release of drug or immediate release drug product. Such immediate release products result in relatively rapid drug absorption and onset of accompanying pharmcodynamic effects. Hence, change in the operation is a suitable and optimized way to make the some drug more effective by slight alteration in the drug delivery. Sustained Release is also providing promising way to decrease the side effect of drug by preventing the fluctuation of the therapeutic concentration of the drug in the body. However after absorption of drug from is complete, plasma drug concentration decline according to the drugs pharmacokinetic profile. Pharmaceutical industries and academic laboratories have been focused on development of novel drug delivery system or modified release dosage form rather investigation and development of new drug. Advance in technology have resulted in novel modified release dosage form. In contrast to conventional form, modified release products provide either delayed release or extended release of drug.

Sustained release matrix type drug delivery system: a review

A bioinformatic approach to identify core genome difference between Salmonella Pullorum and Salmonella Enteritidis In silico screening of natural compounds against COVID-19 by targeting Mpro and ACE2 using molecular docking

Burden of Prior Authorization Requirements on Urology Practice and Patients.

ABSRACT The objective of present investigation was to isolate the phytochemical component, limonene from the peels of Citrus sinensis belonging to family Rutaceae and formulate anti-emetic nasal spray. Limonene loaded colloidal dispersion was prepared by using various polymers like HPMC, DSHOP, and surfactant as Tween 80. Further the formulation was evaluated for its clarity, pH, viscosity, pka, pump delivery, net content, and droplet diameters. Limonene was obtained by steam distillation method and subjected to its phytochemical screening and Pharmacopoeial procedures were used to study the, solubility, organoleptic properties, pH, viscosity, pka , pump delivery, net content, droplet diameters. The pH of the formulation was adjusted between 5.0-5.5 which is nonirritant for nasal delivery system. The result showed that the optimized formulation was found to be colorless, orange like odor and shows adhesive property. The adhesive property in the formulation is because of the presence of mucoadhesive polymer, which prolongs the effectiveness of dosages form by its mucoretentive effect onto the nasal mucosa. To evaluate the spray related property, a plastic spray container was selected and evaluated for the release of net content which was found to be 20 ml and total spray pattern of the formulation was found to be 322 sprays. The above study shows that the limonene loaded antiemetic formulation can be given via nasal route to enhance the effectiveness as well as onset of action.

Vikas Bhatt

Papers

In silico screening of natural compounds against COVID-19 by targeting Mpro and ACE2 using molecular docking.

Sustained release matrix type drug delivery system: a review

A bioinformatic approach to identify core genome difference between Salmonella Pullorum and Salmonella Enteritidis In silico screening of natural compounds against COVID-19 by targeting Mpro and ACE2 using molecular docking

Burden of Prior Authorization Requirements on Urology Practice and Patients.

Formulation and evaluation of antiemetic nasal spray of limonene.