DEVELOPMENT OF ALBUMIN BASED NANOPARTICLES FOR BIOMEDICAL APPLICATIONS

Abstract

The last two decades have witnessed an unprecedented growth in the field of biomedical nanotechnology. A vast variety of nanomaterials are inspected so far in this campaign but among them only few have succeeded in their clinical trials. However, major drawbacks are associated with these nanoparticles which impede their future implications. In this regard, albumin based nanoparticles have emerged as a promising nano-platform due to their high drug holding capacity, ability to protect entrapped cargo molecules from degradation, improved solubility and bioavailability of drug, enhanced cellular uptake, biocompatible and non immunogenic nature due to its biological origin. Moreover, the presence of functionally charged groups offers albumin with various possibilities for surface modifications and interactions with various nanoparticles and drug molecules. Thus, the current thesis focuses on the development of albumin based nanoparticles and proposes their employment in anticancer and antioxidant applications. In Anticancer applications, albumin nanoparticles based water soluble nanoformulation of highly hydrophobic anticancer drug niclosamide (i.e. BSA-Nic NPs) has been prepared, which overcomes the drawbacks associated with niclosamide such as poor water solubility and limited systemic bioavailability of the drug. Successful synthesis of spherical, highly monodispersed nanoparticles was confirmed by various physicochemical characterization techniques. The therapeutic efficacy of prepared nanoparticles was examined against cancer cells by cell viability assay and morphological analyses. The gene expression analysis confirms the successful induction of apoptosis by these nanoparticles. Another major hurdle in cancer therapy is generalized distribution of therapeutic molecules which results in the implications of higher drug dose that cause severe side effects. In order to address the problems associated with non-specific distribution, cytotoxicity and genotoxicity at higher dose of silver nanoparticles (Ag NPs), a folate conjugated albumin stabilized silver nanoparticles (FA-BSA-Ag NPs) was prepared. The therapeutic potential and cellular uptake was determined on human breast cancer cells, MCF-7 (FR-positive cells) having abundant folate receptor (FR) on its surface and human lung cancer cells, A549 (FR-negative cells). Moreover, the successful induction of apoptosis was confirmed by reactive oxygen species (ROS), cell cycle, morphological and nuclear analysis, followed by apoptotic signalling gene expression analysis. ROS induced oxidative stress is one of the major factors responsible for various diseases and disorders including cancer. In case of excessive oxidative stress the antioxidant enzymes iv defence system of the body gets impaired, which in turn disturb the oxidative balance and cellular homeostasis. Nanoceria (CNPs) has emerged as potential nano-agent in antioxidant therapy because of its exceptional antioxidative activity. In antioxidant applications, a highly biocompatible nanoceria encapsulated albumin nanoparticles (BCNPs) was synthesized, which overcomes the various drawbacks associated with nanoceria such as poor cellular uptake and short residence time in body. Such artificial antioxidant nanozyme protects the cells against actively generating ROS by providing a desired steady state level of therapeutic dose over a period of time as examined in vitro. Furthermore, the gene expression analysis confirms the preservation of antioxidant defence system of the cell and their protection from oxidantmediated apoptosis. Finally, other problems accompanied with nanoceria such as poor solubility and use of harmful chemicals during preparation was addressed by synthesizing albumin coated nanoceria (ANC) by alkaline based precipitation method without altering their antioxidative property. These nanoparticles were highly biocompatible and provided protection against oxidative stress as examined on both in vitro and in vivo models. In summary, the present study demonstrated the potential of albumin based nanoparticles in anticancer and antioxidant applications. Such nanoparticles open up a new avenue for the development of improved nano-drug therapies for future clinical trials.