Polymeric carriers for drug and gene delivery have been successfully used in clinical applications, and developing to achieve greater efficacy. A successful polymeric carrier must not only protect the therapeutics from degradation but also increase the pharmacokinetic and biopharmaceutical properties of the therapeutic agents. Furthermore, releasing the therapeutic agents from nanocarriers at the desired target sites and with the correct dosage is important to enhance patient outcomes.Numerous polymeric systems for drug and gene delivery that can release bioactive agents through response to external (e.g., light, electric or magnetic source, and ultrasound) or internal triggers (e.g., pH, enzyme, and redox) have been designed. However, release mechanism using these triggers is restrictive in terms of in vivo applications as there is limited accessibility of external stimuli to tissues or organs; and the efficiency of internal triggers are variable between cell lines and even within the same tissue or organ. Some carriers are not degradable, raising the important issue of toxicity due to accumulation in the body and healthy cells. In addition, the time of release is mostly uncontrollable. The main aim of this thesis is to synthesize and study of novel non-triggered and timed-release polymeric carriers, such as micelles and hydrogel, based on thermoresponsive PNIPAM and self-degradable PDMAEA. In particular, we developed the understanding of the selfassembly and disassembly properties of thermoresponsive PNIPAM copolymerized with the selfdegradable PDMAEA and hydrophobic components. This is one of the first examples where the disassembly time can be controlled on-demand in a wide range of experimental conditions. Initially, the self-catalysed hydrolysis of PDMAEA together with hydrophobic polymers were employed to finely tune the LCST and disassembly time of thermoresponsive PNIPAM and thus control the release time of oligo DNA (i.e., mimic of siRNA) from the polymer complex. The diblock thermoresponsive copolymers were synthesized by Reversible addition-fragmentation chain transfer (RAFT) polymerization, which consisted of a hydrophilic block (e.g., PDMA) for stabilization and a second thermoresponsive block with three components (e.g., NIPAM, DMAEA, and BA or Styrene) for self-assembly and disassembly. The copolymers were fully water-soluble below LCST and self-assembled into core-shell spherical particles with an average diameter of approximately 25 nm above LCST (e.g., 37 o C) and with a narrow particle size distribution. When the amount of acid groups from degradation of cationic DMAEA units was sufficiently high to increase LCST of the copolymer above 37 °C, the polymer nanoparticles sharply disassembled to unimers (i.e., the core of the copolymer became water soluble). These nanoparticles showed excellent binding to oligo DNA without any leakage until full disassembly to unimers. Interestingly, the disassembly time of the nanoparticles and consequently the release time of oligo DNA could be precisel...
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