Facile Grafting Of Natural Drugs And Silver Nanoparticles Into Metal-Organic Frameworks For Their Biological Applications

Nowadays,the growth of drug-resistant bacteria has become one of the most serious concerns and threats to public health.There has always remained a battle between humans and multiple microorganisms which results into infections and disease.Antibiotics have played a significant role in treatment of various contagious diseases but the inappropriate,irrational and irregular uses of antibiotics are resulted in to the propagation of selective pathogenic bacteria resistant to multiple drugs.Such antimicrobial resistance has caused millions of infectious diseases and loads of deaths every year around the world.During past decades,the continual substantial reduction in effectiveness of various approved antibiotics has established a threatening and grave situation.To overcome such serious problem of microbial resistance to drugs,the creation of novel active compounds against new targets or modifications in already existing ones to improve their antimicrobial activity has become very crucial.Therefore,several innovative methods and approaches are being studied for the treatment of infections caused by multidrug-resistant bacteria.Since 30-50%of current pharmaceuticals and nutraceuticals are plant-derived hence this has increased the interest of researchers in medicinal plants.However,some of the crude drugs originated from plants have poor bio-stability so synthesizes of new compounds is necessary which increase the properties of these crude drugs in biological applications Furthermore,nanotechnology also deliver a good support to alter physical and chemical properties of various materials that can be hitched with bio-applications.Recently metal-based frameworks have also been emerged to be the novel agents for drug delivery,control of microbial diseases and for various pharmacological applications.Metal-organic frameworks can be served as carriers for drugs as well as for active metal nanoparticlesConsidering the indispensable need of the time and aforementioned facts,we have selected the innovative and little explored area where MOFs are taken as drug carrier to increase stability and microbial activity of drugs.The present thesis is composed of three projects which consists of encapsulation of natural drugs i.e.(1)physcion(PHY)(2)gentiopicroside(GPS)into zeolitic imidazolate ZIF-8 MOFs and(3)grafting of silver nanoparticles(AgNPs)into copper and guanosine 5'-monophosphate MOFs(AgNPs@Cu/GMP).The synthesized materials encapsulated into MOFs were characterized through different available techniques,which confirmed the successfully synthesis of natural drugs and silver nanoparticles in MOFs.These encapsulated materials into MOFs shown the remarkably stability and favorable antibacterial activity against gram positive and negative bacterium.Project 1:In this work,natural drug PHY was loaded into ZIF-8 MOFs by applying straight forward nano-precipitation method.The high drug loading efficiency of PHY encapsulated into ZIF-8 was observed as about 88%,besides the drug loading capacity was 11.49%.The PHY@ZIF-8 was characterized through various techniques namely UV-vis spectroscopy,powder x-ray diffraction(PXRD),transmission electron microscopy(TEM),scanning electron microscopy(SEM),thermal gravimetric analysis(TGA)and FT-IR.In acidic medium(pH 5.0),the release of PHY drug from synthesized material PHY@ZIF-8 was three-fold i.e 88.72%than its release in physiological medium(pH 7.4)i.e.27.61%.The PHY@ZIF-8 NPs are stable and effective because significant stability was observed even after 25 days.Moreover,the antibacterial-activity of PHY@ZIF-8 as well as pure drug PHY and ZIF-8 was examined against gram negative and positive strains The PHY loaded into ZIF-8 exhibited significantly higher inhibition zones against all tested microorganism when compared with pure drug PHY and ZIF-8.It is anticipated that this model drug can be suitable for treatment of different infectious diseases.Project 2:In present study,multifunctional natural drug GPS has been encapsulated into ZIF-8 in aqueous solution at room temperature.ZIF-8 MOFs were observed to be suitable and favorable carrier for delivery of GPS.The single step synthesis of GPS@ZIF-8 reflected high loading efficacy of GPS into ZIF-8 of about 84%,while,its loading capacity was revealed to be 10.77%,GPS@ZIF-8 and ZIF-8 were characterized through different techniques.Morphology of GPS@ZIF-8,assessed through SEM and TEM,revealed to be uniform and hexagonal shape which is much alike to pure ZIF-8.Moreover,average particle size distribution of ZIF-8 and GPS loaded into ZIF-8,as observed through DLS,was 125 nm and 149 nm,respectively;increased size of GPS@ZIF-8 depicted a well efficient encapsulation of GPS.The thermal stability showed that the GPS when loaded into ZIF-8 was thermally stable up to 298?.The release profile of GPS drug from GPS@ZIF-8 was studied at 37? in PBS solution with two pH i.e.5.0 and 7.4.The GPS@ZIF-8 reflected significant faster release of GPS in acidic medium i.e.81.31%which was higher than the release of GPS in physiological medium i.e.20.03%.Thus,results of the present study revealed that the ZIF-8 can be used as a potential carrier for controlled delivery of GPS against carcinoma cells in future.Project 3:Silver nanoparticles are effective antibacterial agent but they have some limitations such as less stability and rapid aggregation,which affects their antibacterial efficiency in biomedical applications.To overcome these shortcomings,various strategies have been adopted so far,such as encapsulation of silver nanoparticles in several inorganic and organic ligands.Accordingly,in this study the successful facile grafting of silver nanoparticles into copper and guanosine 5'-monophosphate(Cu/GMP)metal organic framework(MOFs)was done at room temperature without using any external stimuli.The loading encapsulation ratio of AgNPs was approx.99.83%in Cu/GMP(MOF)at neutral pH.All the applied techniques have confirmed the formation of AgNPs loaded in Cu/GMP(MOF).Furthermore,the antimicrobial activities of AgNPs,Cu/GMP and AgNPs@Cu/GMP were assessed against gram negative and gram-positive bacterium.As compared to silvers nanoparticles,the AgNPs loaded Cu/GMP had shown significant growth of inhibition zones against bacteria under test.The remarkable stability of AgNPs@Cu/GMP nanoparticles was observed b ecause,it sustained more i.e.approx.6 times higher than free AgNPs even after fifteen days,this makes it as an effective and potential candidate for biomedical applications.On other hand,the minimum inhibitory concentration(MIC)values show that AgNPs@Cu/GMP is good disinfectant agent against micro-organisms.The results highlight that the AgNPs encapsulated into metal organic framework of Cu/GMP could be a promising antimicrobial agent against various infections and it may deliver an advance platform in pharmaceuticals and various other biomedical applications.