Photodynamical studies of several drug molecules in Chemincal and Biological Cavities.

Resumen

The aim of this dissertation is to understand the nature of the interactions between several drugs and chemical (ß-CD and derivatives) and biological (HSA protein) nano-cavities using steady-state (UV-visible absorption and emission) and time-resolved (time-correlated single-photon counting, fluorescence up-conversion, flash photolysis and stopped-flow) spectroscopic techniques. In chapter 1, the recent developments in drug delivery systems have been reviewed, and the importance of spectroscopic methods in characterizing these systems has been elucidated. Chapter 2 contains detailed information of the materials and the experimental setups used in this thesis. In chapter 3, we have explained the effect of the nano-confinement provided by the chemical and biological hosts on the photophysical and photochemical properties of the caged guest molecules by utilizing steady-state and time-resolved spectroscopic methods. In chapter 3.1, we have shown that the photo-behavior of lumichrome complexed with ß-CD is similar to that in water, while its photodynamics is altered significantly upon complexation with the HSA protein due to an electron transfer between HSA and lumichrome and the cavity protection from bulky water. In chapter 3.2 and 3.3, we found that the photodymics of topotecan was largely affected by the H-bonding environment and the pH of the media. Furthermore, in chapter 3.4, topotecan shows higher affinity towards TM-ß-CD compared to ß-CD and DM-ß-CD in terms of encapsulation, which implies that topotecan requires a highly hydrophobic delivery system. In chapter 3.5 and 3.6, studies on the interaction of a porphyrin derivative (TSPP) with cationic derivative of ß-CD (QA-ß-CD), covalently linked ß-CD dimer (CD-CD) and the HSA protein are presented. It has been found that TSPP/CD-CD is effective in inhibiting the formation of aggregates of TSPP. Additionally, encapsulation by CD-CD does not change the efficiency of singlet oxygen generation by TSPP, hence showing promising characteristics as nano-carrier for this type of systems. Chapter 4 concludes the most important information acquired from this work.