SILVER NANOPARTICLE AND GRAPHENE OXIDE BASED NANOCOMPOSITES FOR BIOMEDICAL APPLICATIONS

Abstract

Nanomedicine promises to solve major healthcare challenges including the antibacterial and anticancer therapy. Regardless of ongoing preclinical research, debatably the key challenge remains its clinical translation. The key complications of nanomedicine is their water insolubility, nanoparticle aggregation in vivo, poor bioavailability, biocompatibility, drug loading, short circulation time, chances of drug resistance, tumour reoccurrence and nonspecific cellular uptake etc. Nanomedicine has provided new avenues for therapeutics by enhancing the current systems through novel nanomaterials. Thus the current thesis focuses on development of silver nanoparticle (Ag NP) and graphene oxide (GO) based nanocomposite materials to address these health care challenges. First part of the study focuses on exploration of simplistic in situ synthesis method for Ag NP incorporated composite nanofiber. Synthesis was validated by various characterization methods. The surface roughness (Sa.), and wettability analysis suggests the suitability of the composite nanofibers as wound dressing. The nanofiber showed antibacterial potential against recombinant green fluorescent protein (GFP) expressing antibiotic-resistant Escherichia coli (E.coli). Therefore, the nanofibers fabricated by this approach could serve as wound dressing for long term effectiveness with controlled release system. Furthermore in pursuit to develop antimicrobial wound dressing with advanced features, the properties of GO were exploited. The presence of ample oxygenated groups confers GO versatility for development of nanocomposites. Curcumin (CUR), a traditionally known component of turmeric, is also known for its remarkable antimicrobial activity. Hence the antibacterial and physiochemical properties of GO, Ag NP, chitosan (CS) and CUR were exploited for fabrication of biocompatible composite nanofiber. The Poly(ethylene glycol) (PEG) functionalized GO was synthesized, as PEG provide GO the physiological stability. It was also served as template for Ag NP synthesis. The antibacterial potential of composite nanofiber was evaluated against Gram positive and Gram negative bacteria. The nanofiber possessed enhanced mechanical and antibacterial property with negligible cytotoxicity against fibroblast cells (NIH-3T3) with better cell adhesion and proliferation. The next part of study focuses on the current cancer challenges including water insolubility of anticancer drugs, and localized tumour reoccurrence after surgery. In an effort to enhance the water solubility of hydrophobic drug niclosamide (nic), a simplistic method based on amorphous solid dispersion and solvent evaporation was explored as promising strategies to iv improve its bioavailability. A hydrophilic polymer matrix was selected for solid dispersion to improve its properties. Electrospinning was adopted among various solvent evaporation methods and thus nanofiber based drug delivery system (DDS) was designed for localized codelivery of Ag NP and nic (nic@Ag NP) for cancer therapy. The various formulations of composite nanofibers were well-characterized and in vitro release and kinetic studies suggest sustained release with Fickian diffusion kinetics. The antitumor potential of the nic@Ag NP loaded nanofibers were evaluated against A549 (lung carcinoma) and MCF-7 (breast carcinoma) cell lines. The co-delivery of anticancer drugs nic@Ag NP displayed the superior antitumor potential against both cell lines in vitro when compared to their individual effects. The cell death mechanism was explored which clearly explains the remarkably improved therapeutic efficacy of combined effect. To address the cell specific delivery of anticancer agents, GO was exploited as a nanocarrier based on its advantageous features, including the ease of surface functionalization, amphiphilicity, and high drug loading capacity Folate receptor (FR) targeted GO based codelivery system of anticancer agents (tamoxifen (TAM)/Ag NP) for breast cancer therapeutics was developed. Though TAM is clinically used for breast carcinoma, but it lacks full potency based on water insolubility. In order to enhance its water solubility and bioavailability, it was loaded into the folic acid (FA) functionalized GO (FA-GO). TAM was co-loaded with Ag NP to investigate their combination effect. Remarkably the study suggests the targeted DDS (FAGO@ Ag NP@TAM nanocarrier) based combination therapy could be a promising alternative for enhanced therapeutic effect at lower concentration against breast cancer. Noteworthy the present study has demonstrated the Ag NP and GO based nanocomposite materials which offers considerable potential for antibacterial and anticancer therapeutics, hence opens new prospect for Ag NP and GO based nanomedicine.