Application of Mesoporous Silica nanoparticles as a nano carrier for the treatment of HCV and HIV infections

Abstract

Carrier-mediated drug delivery systems have emerged as a powerful tool for the treatment of various diseases, especially, in the field of viral infection. The therapeutic index of traditional and novel anti-virals are heightened through the enhancement in their target specificity. Anti-virals can be delivered at the targeted site without any degradation with the support of a nano-carrier. Viral disease treatment needs an upgraded drug delivery system to reduce the dosage and systemic toxic effects along with improved pharmacokinetic properties of anti-viral therapeutics. In this thesis, mesoporous silica nanoparticle (MSN) based delivery system was synthesized to deliver therapeutic agents to increase their efficiency and bioavailability. Functionalization was carried as per the requirement. The synthesized delivery vector was characterized using different techniques. The ability of MSN to interact with therapeutic agents was also evaluated. Toxicity studies using cell cultures and animal models assured the non-toxic properties of this delivery vector. The as prepared nanocarrier was able to mediate efficient transfection in mammalian cells. Preferential delivery of drugs was proven using both in vitro as well as in vivo models confirming the target-specific nature of this MSN based delivery system. Targeted delivery of small hairpin DNA (shDNA) to liver using MSN based nano-carrier to combat hepatitis C virus (HCV) infection was investigated. MSN was amine functionalized to achieve electrostatic interaction between the nanoparticle and DNA. Galactose functionalization ensured the preferential delivery to the liver through the ligand asialoglycoprotein receptor interaction abundantly present on liver cell surface which was visualized in the in vivo model. Significant reduction (about 94 %) of viral RNA level was achieved which confirmed the successful delivery and action of the shDNA...