Study on Self-Assembly of Fullerenes and Biopolymers

The understanding of self-assembly processes is important for fabrication of well-defined structures with new functionalities for applications in the area of biomedical sciences, material sciences and electronics. In this thesis, two types of self-assembly processes are described: (1) self-assembly of fullerene derivatives in water and (2) self-assembly on surfaces using layer-by-layer (LbL) approach. The various interactions and parameters involved in the self-assembly are detailed in the introductory chapter 1. The various internal parameters like molecular geometry, intramolecular and intermolecular forces that guides the self-assembly process of amphiphiles in water are discussed. The experimental procedures used in the present thesis for the fabrication of nanostructures via self-assembly approach are also described. In the later part of the chapter, the LbL technique for fabrication of thin films and microcapsules is reviewed where various interactions involved in the growth of LbL assembly are discussed. The effect of ionic strength and pH on the growth and property of LbL assemblies is elaborated. A brief discussion of the materials used in the thesis ‒ fullerene, bovine serum albumin (BSA) and nanocrystalline cellulose (NCC) is also provided The self-assembly behaviour of amphiphilic fullerene derivatives are described in chapter 2. Fullerene is anisotropically substituted with five polar hydroxyl groups using organo-copper reagent. The derivative can interact in water via the van der Waals and hydrophobic interactions of the fullerene moiety as well as the intermolecular hydrogen bonding among the hydroxyl groups and also with water. The penta-hydroxy fullerene derivative self-assembles in water as vesicular structures. The size of these vesicles can be varied by modifying the kinetics of self-assembly which was done by changing the rate of addition of non-solvent (water) to the solution of the fullerene derivative. In the second derivative, the hydroxyl groups are substituted with less polar methoxy groups. The penta-methoxy fullerene derivative cannot participate in inter-molecular hydrogen bonding formation unlike the penta-hydroxy derivative but there is possibility of hydrogen bond formation with water where oxygens on methoxy group can act as hydrogen bond acceptor. The penta-methoxy fullerene does not show any vesicle formation in water. The computational simulation studies were carried out on the two fullerene derivatives to understand the self-assembly behaviour of these two derivatives. Furthermore, the vesicle structures formed by the penta-hydroxy fullerene derivative are used for entrapment of hydrophobic polymer, poly[2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylenevinylene] (MEH-PPV) and also hydrophilic dye, Rhodamine B. In both the cases, fluorescence quenching is observed due to electron transfer reaction with fullerene and hence these fullerene vesicles can be used to study the effect of confinement on electron transfer reactions and other chemical dynamics. The layer-by-layer self-assembly approach for the fabrication of biopolymeric thin films and microcapsules is discussed in the chapters 3 to 6. The biocompatible nanoparticles and nanofibers were used as the components of the assembly. In chapter 3, we have described fabrication of thin film of bovine serum albumin (BSA) nanoparticles via LbL approach using biopolymer chitosan as the complementary polymer. The driving force for the assembly growth of the assembly was the electrostatic and complementary hydrogen bond formation between the two components. The idea of incorporating nanoparticles in the thin film was that the nanoparticles can act as reservoirs for functional materials. The films were loaded with anticancer drug doxorubicin and show pH dependent release of the drug. The various interactions involved in the LbL assembly of BSA nanoparticles and polymers were investigated towards understanding the growth mechanism of the assembly in chapter 4. The understanding of the interactions involved in the assembly formation is important in order to modify the conditions of the assembly for enhancing the growth. It is inferred from the study reported in this chapter that not only the interaction of nanoparticles with polymers but also the inter-particle interactions are important factors in determining the growth of LbL assembly of nanoparticles/polymers. The growth of the assembly is enhanced on minimizing the inter-particle repulsions, which was achieved in case of BSA nanoparticles by modifying the pH of the assembly. We also utilized the LbL self-assembly approach for the delivery of lipophilic drugs. The lipophilic drugs are difficult to administer in the body due to their poor water solubility and hence show poor pharmacokinetic profile. The methods for incorporating hydrophobic drugs in LbL assembled thin films and microcapsules are described in chapters 5 and 6. In chapter 5, hydrophobic molecules binding property of albumin has been exploited for solubilisation of a water-insoluble molecule, pyrene (model drug) and hydrophobic drug, curcumin, by preparation of non-covalent conjugates with BSA. The interaction with BSA provided negative zeta potential to the previously uncharged molecules and hence they can be incorporated in the LbL assembled thin films and microcapsules using electrostatic as well as hydrogen bonding interaction with biopolymer, chitosan. The fabrication of protein encapsulated stable microcapsules with hydrophobic molecules incorporated in the shell of the microcapsules has also been demonstrated. The microcapsules were further capable of loading hydrophilic molecules like Rhodamine B. Thus, this approach can be employed for fabrication of multi-agent carrier for hydrophobic and hydrophilic drugs as well as therapeutic macromolecules. In chapter 6, we have incorporated nanocrystalline cellulose (NCC) LbL assembled thin films and microcapsules. The assembly formed was porous in nature due to the nano-fibrous morphology of NCC. The nanoassemblies can act as potential drug delivery carrier, which has been demonstrated by loading anticancer drug doxorubicin, and a lipophilic drug, curcumin. Doxorubicin hydrochloride, the salt form of the drug, doxorubicin, has good water solubility and hence can be postloaded in the assembly by diffusion from its aqueous solution. In the case of curcumin, which has limited solubility in water, a stable aqueous dispersion of the drug was prepared via noncovalent interaction with NCC prior to incorporation in the LbL assembly. The interaction of various other lipophilic drugs with NCC was analysed computationally