Smart polymeric prodrugs for targeted drug delivery and functionalizable hydrogels for biosensing applications

Abstract

Biosensing applications have an enormous place for diagnosis of numerous diseases. New platforms and materials have been developed to detect markers for several diseases. However, well defined materials are required for specific and sensitive detection of biological compounds. Dendrons and dendrimers with multifunctional properties possess several advantages for designing such materials. The first part of this dissertation focuses on designing well-defined hydrogel systems by introducing functionalizable dendrons into the network as 3-D platforms for biosensing applications. Two different approaches were described for the formation of functionalizable hydrogels and control over the degree of hydrogel functionalization was successfully demonstrated. The discovery of enhanced permeability and retention (EPR) effect, anti-angiogenic therapy and new targeting strategies have prompted researchers for designing prodrugs for cancer therapy. Although investigations have focused on various drawbacks and obtained promising developments in macromolecular prodrug design, better pharmacokinetic and biodistribution parameters and more effective strategies are required to achieve better therapeutic results. Stealth and inactivity of anti-cancer drugs in blood and healthy tissues is desired to decrease systemic side effects. Effective transport and release of the active agent at the target tissue is an attractive approach to improve therapeutic effect. The second part of this dissertation includes design and in vitro and in vivo evaluations of smart polymeric prodrugs for drug delivery applications. Polymer drug conjugates and polymeric micellar type prodrugs were designed to increase solubility and improve pharmacokinetic and therapeutic properties of the anti-mitotic and anti-angiogenic drugs. Targeting and controlled drug release properties were introduced by covalent attachment of a targeting ligand and using enzymatically cleavable or pH sensitive linkers. Stealth of the active agents was enhanced by branching strategy obtained by oligo ethylene glycol side chains on the polymer backbone and/or by encapsulation into the hydrophobic core of the micelles.