Development and Characterization of Thiolated Cyclodextrin-Based Nanoparticles for Topical Delivery of Minoxidil.

PURPOSE: The aim of this research was to prepare adhesive nanoparticles for the topical application of Minoxidil (MXD). METHODS: Thiolated ß-CDs were prepared via conjugation of cysteamine with oxidized CDs. MXD was encapsulated within thiolated and unmodified ß-CDs. Ionic gelation method was used to prepare nanoparticles (Thio-NP and blank NP) of CDs with chitosan. Nanoparticles were analyzed for size and zetapotential. Inclusion complexes were characterized via FTIR. Drug dissolution studies were carried out. An in vitro adhesion study over human hair was performed. An in vivo skin irritation study was performed. Ex vivo drug uptake was evaluated by using a Franz diffusion cell. RESULTS: Thiolated ß-CDs presented 1804.68 ± 25 µmol/g thiol groups and 902.34 ± 25 µmol/g disulfide bonds. Nanoparticles displayed particle sizes within a range of 231 ± 07 nm to 354 ± 13 nm. The zeta potential was in the range of -8.1 ± 02 mV, +16.0 ± 05 mV. FTIR analyses confirmed no interaction between the excipients and drug. Delayed drug release was observed from Thio-NP. Thio-NP retained over hair surfaces for a significantly longer time. Similarly, drug retention was significantly improved. Thio-NP displayed no irritation over rabbit skin. CONCLUSION: Owing to the above results, nanoparticles developed with MXD-loaded thiolated ß-CDs might be a potential drug delivery system for topical scalp diseases.

Virtual Screening of Phytochemicals by Targeting HR1 Domain of SARS-CoV-2 S Protein: Molecular Docking, Molecular Dynamics Simulations, and DFT Studies.

The recent COVID-19 pandemic has impacted nearly the whole world due to its high morbidity and mortality rate. Thus, scientists around the globe are working to find potent drugs and designing an effective vaccine against COVID-19. Phytochemicals from medicinal plants are known to have a long history for the treatment of various pathogens and infections; thus, keeping this in mind, this study was performed to explore the potential of different phytochemicals as candidate inhibitors of the HR1 domain in SARS-CoV-2 spike protein by using computer-aided drug discovery methods. Initially, the pharmacological assessment was performed to study the drug-likeness properties of the phytochemicals for their safe human administration. Suitable compounds were subjected to molecular docking to screen strongly binding phytochemicals with HR1 while the stability of ligand binding was analyzed using molecular dynamics simulations. Quantum computation-based density functional theory (DFT) analysis was constituted to analyze the reactivity of these compounds with the receptor. Through analysis, 108 phytochemicals passed the pharmacological assessment and upon docking of these 108 phytochemicals, 36 were screened passing a threshold of -8.5 kcal/mol. After analyzing stability and reactivity, 5 phytochemicals, i.e., SilybinC, Isopomiferin, Lycopene, SilydianinB, and Silydianin are identified as novel and potent candidates for the inhibition of HR1 domain in SARS-CoV-2 spike protein. Based on these results, it is concluded that these compounds can play an important role in the design and development of a drug against COVID-19, after an exhaustive in vitro and in vivo examination of these compounds, in future.

Process optimization for enhanced production of cellulases form locally isolated fungal strain by submerged fermentation

Cellulase has myriad applications in various sectors like pharmaceuticals, textile, detergents, animal feed and bioethanol production, etc. The current study focuses on the isolation, screening and optimization of fungal strain through one factor at a time technique for enhanced cellulase production. In current study sixteen different fungal cultures were isolated and the culture which quantitatively exhibits higher titers of cellulase activity was identified both morphologically and molecularly by 18S rDNA and designated as Aspergillus niger ABT11. Different parameters like fermentation medium, volume, temperature, pH and nutritional components were optimized. The highest CMCase and FPase activities was achieved in 100ml of M5 medium in the presence of 1% lactose and sodium nitrate at 30 oC, pH5 after 72 hours. The result revealed A. niger can be a potential candidate for scale up studies.

Insights into the inhibitory potential of selective phytochemicals against Mpro of 2019-nCoV: a computer-aided study.

At the end of December 2019, a novel strain of coronavirus, given the name of 2019-nCoV, emerged for exhibiting symptoms of severe acute respiratory syndrome. The virus is spreading rapidly in China and around the globe, affecting thousands of people leading to a pandemic. To control the mortality rate associated with the 2019-nCoV, prompt steps are needed. Until now there is no effective treatment or drug present to control its life-threatening effects in the humans. The scientist is struggling to find new inhibitors of this deadly virus. In this study, to identify the effective inhibitor candidates against the main protease (Mpro) of 2019-nCoV, computational approaches were adopted. Phytochemicals having immense medicinal properties as ligands were docked against the Mpro of 2019-nCoV to study their binding properties. ADMET and DFT analyses were also further carried out to analyze the potential of these phytochemicals as an effective inhibitor against Mpro of 2019-nCoV.

In Silico Computations of Selective Phytochemicals as Potential Inhibitors Against Major Biological Targets of Diabetes Mellitus.

BACKGROUND: In the past few years, several developments have been made to understand and control the complications and harmful side-effects associated with the disorder diabetes mellitus (DM). Many new steps have been taken in a better understanding of the pathophysiology of the disease. With the advancement in the field of medical sciences, various novel therapies have been developed to efficiently control the pathological effects of diabetes mellitus. Recently, phytochemicals possessing various medicinal properties have opened up a new vast range of opportunities to design novel therapeutic drugs against diabetes mellitus. OBJECTIVE: The present study aims to identify and screen phytochemicals as potent and novel inhibitors against diabetes mellitus. METHODS: Three major biological targets of diabetes mellitus named Cytochrome P450, glycogen synthase kinase and PPARγ are targeted using phytochemicals by performing pharmacological properties prediction, molecular docking and density functional theory studies. RESULTS: Out of 108 phytochemicals, 20, 12 and 3 phytochemicals showed higher binding affinity values as compared to chemically synthesized drugs against cytochrome P450, glycogen synthase kinase and PPARγ, respectively. CONCLUSION: The screened phytochemicals have strong inhibitory potential against diabetes mellitus and in future, these compounds, holding immense potential, can be considered as candidate drugs for treating diabetes mellitus.