Development of micellar novel drug carriers utilizing temperature-sensitive block copolymers containing cyclodextrin moieties

摘要

The objective of this thesis is to investigate well-defined nanoparticles as potential drug delivery systems. To achieve this aim, the block copolymers were synthesized using the Reversible Addition Fragmentation Chain Transfer (RAFT) process and conjugated with β-cyclodextrin moieties using click chemistry to obtain amphiphilic characteristics. Huisgen azide-alkyne 1,3-dipolar cycloaddition and thiol-ene click reactions were used for post-modification of block copolymers. Upon heating above the lower critical solution temperature (LCST) of the block copolymers, the β-cyclodextrin-based block copolymers undergone self-assembly in aqueous environment to form micelles. These nanostructured particles were capable of carrying drugs, both in the hydrophobic core and the β-cyclodextrin cavities. The drug loading efficiency was increased by means of acetylation and cross-linking. The conjugation of β-cyclodextrin to block copolymers reduced its toxicity and capable of dissolving more hydrophobic drugs, while big enough in size to behave as drug delivery systems.