Sapthasri, R (2021) Silymarin Loaded Super Paramagnetic Iron Oxide Nanoparticle (SPIONS) for Targeting SARS COV-2 to Combat COVID-19. Masters thesis, College of Pharmacy, Sri Ramakrishna Institute of Paramedical Sciences, Coimbatore.
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Abstract
On March 11, 2020, the WHO declared the COVID-19 outbreak a pandemic. As of May 2020, SARS-CoV-2 has spread across the world in over 185 countries, with millions of infections and hundreds of thousands of deaths. Nanotechnology offers a number of solutions to fight viruses, both outside and inside the host, and several nanotechnology-based platforms have already been successful in preclinical studies to counter several human viral pathogens such as HIV, human papilloma virus, herpes simplex, and respiratory viruses. Magnetic nanoparticles (MNPs) which exhibit para magnetism in the absence of external magnetic field. However, MNPs display super-para magnetism in the presence of magnetic field which helps to target at particular site by using external magnet as it contain exceptional optical, electrical and chemical properties which permit their applications in virus detection, magnetic cell separation, enzyme catalysis, gene therapy, targeting chemotherapy, radiotherapy, diagnostics, therapeutics, bio-sensing and information storage. Magnetic nanoparticles exhibiting such properties offer vast advantages over traditional macro or microparticles in targeted drug delivery and treatment. Silymarin, a potential phytochemical compound obtained from the seeds of Silybum marianum (milk thistle) plant has been used as a hepatoprotective agent, and shows strong anti-oxidant effect. Now evidence suggests that the extract possesses potent antiviral activities against numerous viruses, particularly hepatitis C virus (HCV). Consequently, silymarin is the most commonly consumed herbal product among HCV-infected patients in western countries. Antiviral efficacy of silymarin has also been reported against human papillomavirus, a highly carcinogenic virus. Various antiviral activities of silymarin and derivatives have been shown against liver and non-liver pathogens, making them potential broad-spectrum antivirals, for some of the enveloped viruses explored to date. The high incidence of administration of silymarin together with its short half-life and poor bioavailability proposed great scope for the proposal of nanoparticulate drug delivery systems. The aim and objective of this project is to contribute towards covid-19 and also target the affected site of lung for better bioavailability and to reduce the further toxicity. The binding ability of silymarin with the receptor was assessed by comparing to the standard drug Remdesivir by molecular docking. In this present work silymarin magnetic nanoparticle has been formulated with three different types of polymers (Ethyl cellulose, Eudragit, Polyethylene glycol) by co- precipitation method. Molecular docking study was carried out to evaluate the most preferred geometry of the protein ligand complex. Homosapien covid receptors were used for performing docking study as target proteins. Various Homosapien receptor were selected and docked. The best binding receptors were further compared with the standard ligand. Remdesivir is the selected standard as it is the most potent currently used Anti-viral drug. Among various Covid -19 receptors docked, 5N11, 7JMP,7JMO with -8.09, -7.23, -6.96 has showed more binding ability towards silymarin then that of the standard drug Remdesivir. Preformulation studies were carried out to find out the solubility of Silymarin. Solubility test gave an idea that silymarin is not water soluble but soluble in solvents like acetone, dichloromethane etc. FTIR and UV spectral studies authenticate the spectra obtained with the sample drug matched with standard pure drug. UV spectra gave the maximum absorption peak at 288nm.The comparison of FTIR spectra of Silymarin and mixture of Silymarin and polymer confirms that there is no appearance of additional new peaks and disappearance of existing peaks from that of the drug. This indicates that there is no interaction between the drug and polymer used in the study. Super Paramagnetic Iron Oxide Nanoparticle (SPIONs) was carried out by Co- precipitation method. This method was simple and cost effective. The percentage yield is low in formulation F1,F2,F3 and F4 ie, below 30% and high in formulation F5, F6, F7 and F8 (78.16 %). It can also be noted that the yield obtained while using ethyl cellulose as polymer is much higher when compared with eudragit and polyethylene glycol. Since the yield is less in formulations F1-F5 with Eudragit, they are not considered for further studies. The entrapment efficiency was found to be highest for F8 formulation (Silymarin: ethyl cellulose, ratio 1:2) which is 96.43% and the lowest entrapment of drug was found for F11 formulation (Silymarin: polyethylene glycol ratio 1:2) which is 80.15%. Since the entrapment efficiency is high 96.43% and particle size is less 319 nm for formulation F8 among other formulation, it is considered for Zeta potential measurement and SEM analysis. Scanning electron micrograph of the prepared magnetic nanoparticle at different magnification showed that the nanoparticle were polydispersed spherical shape. The spherical and polydispersed nature of magnetic nanoparticle was clearly observed in the SEM images. Particle size and zeta potential was determined by Malvern Zeta sizer. The particle size analysis confirmed that the prepared sample were in the nanometre range. Average particle size obtained for the formulation ethyl cellulose F8 was found to be 319 nm. Zeta potential values of magnetic nanoparticle indicated that the formulated magnetic nanoparticle is stable. From the in-vitro release data from the dialysis bag diffusion method it was found that formulations F5, F6, F7, F8, F9, F10, F11 and F12 showed the drug release of 111.26, 98.26, 91.12, 94.12,98.78, 99.78, 99.31 and 97.71 respectively at the end of 24 hours. In-vitro drug release data indicates that both hydrophobic polymer ethyl cellulose and poly ethylene glycol have sustained the release of drug. There is no significant effect in polymer type. Drug release was observed as a function of drug: polymer ratio type. It was observed that the drug release decreased with the increase in the amount of polymer for each formulation of ethyl cellulose and polyethylene glycol. This is due to the drug release is retarded with the difficulty of the drug to diffuse in the increased swollen matrix of the polymer with the higher concentration. The data obtained from the in vitro release study was fitted to the models which were used to find out the mechanism of drug release from silymarin magnetic nanoparticle. The in vitro release model best fitted to Higuchi release order. This was confirmed by plotting percentage cumulative drug release and square root of time and r2 value ranges between 0.8477 and 0.9888. CONCLUSION: The Silymarin magnetic nanoparticle can be formulated by cost effective and easy co-precipitation method using polymers such as ethyl cellulose, eudragit and polyethylene glycol. The formulated silymarin magnetic nanoparticle can be used in the treatment of Covid-19 as it has shown higher binding ability compared to Remdesivir. This can be targeted to the particular site of affected area of lung which in turn reduces the dose, frequency of administration and the side effects. This formulation can be better treatment for Covid-19.
| Item Type: | Thesis (Masters) |
|---|---|
| Additional Information: | 261910159 |
| Uncontrolled Keywords: | Silymarin Loaded Super Paramagnetic Iron Oxide Nanoparticle (SPIONS), Targeting, SARS COV-2, Combat, COVID-19. |
| Subjects: | PHARMACY > Pharmaceutics |
| Depositing User: | Subramani R |
| Date Deposited: | 01 Nov 2022 16:02 |
| Last Modified: | 01 Nov 2022 16:02 |
| URI: | http://repository-tnmgrmu.ac.in/id/eprint/20868 |
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