Structral Design Of Environmental Stimuli-rsponsive Block Copolymer And Study For Drug Controlled Release Behavior

More attentions have been paid on the double hydrophilic block copolymers(DHBCs), due to the block segment generate phase separation and spontaneously self-assemble into nano-structural aggregates, induced by external stimuli such as pH, ionic strength and temperature, and as drug delivery exhibit attractive potential. Among numerous studies, the pH responsive double hydrophilic block copolymers have been the most studied for the multiple self-assembly behaviors induced by the hydrophobic interaction, hydrogen-bonding and electrostatic interaction at the convenient pH changes. While exploring more facile and brief methods for constructing this kind of copolymer and endow it further functionalization property has been a investigation interest.pH responsive block copolymer was constructed via molecular design based on the microenvironment difference(pH) between the cancer cell and normal tissue, and used as anti-cancer drug carrier. By controlling the composition and molecularly structure of this kind polymeric carrier to reduce or avoid the drug release under normal tissue condition and realize the controlling release at cancer cell mildly acid environment. The reported pH responsive polymeric delivery systems such as acylhydrazone, ketal, ortho ester etc. have demonstrated their unique advantages. While the complicate preparation process, efficient release rate and passive delivery to tumor tissue will still limit the practical application. Therefore, design and constructing of new kind of pH responsive block copolymer applied to load and release of anti-cancer drugs is urgent to be undertaken. The reported study has confirmed that environmental stimuli-responsive glycopolymers can bind with phenylboronic acid at basic or neutral condition to form a stable boronate ester but dissociate under acid condition. Furthermore, anti-cancer drugs bearing boronic acid moiety such as Bortezomib can be conjugated to catechol polymeric carriers via reversible dynamic covalent at basic or neutral condition and dissociate from the polymer-bound catechol groups at acid environments, and the pH changes range of conjugation and dissociation between boronic acid moieties of Bortezomib and 1,2 diol unites of polymeric carriers is just matching the difference of mirco-environments between the cancer cell and normal tissue. Yet the reversible dynamic covalently interaction between the glycopolymer bearing large number of 1, 2(1, 3)-diol units and boronic acid is still clearly unknown, thus, fabricating pH responsive block glycopolymer and exploring its the interaction with Bortezomib and used as Bortezomib carriers will further extend the application of the pH responsive block glycopolymer to other boronic acid contained drugs loading and release.In this paper, our work includes two sections. In first section, by structural design, pH responsive PEGylated triblock copolymer comprising carboxyl groups and amine mioties was fabricated via simple ATRP and group protecting chemistry. And the self-assembly behavior of pH responsive PEGylated triblock copolymer by pH changes was studied. In second section, PEG-b-PGAMA was synthesized and used to verify whether the glycopolymer could bind with the Bortezomib at basic or neutral conditions and investigating the loading and release for Bortezomib. Based on the results, constructing two different kinds of glycopolymers with pH responsive block and none pH responsive block, used as Bortezomib carrier, and exploring how the inner core of their assembled aggregates changes under different pH affect the release profile of Bortezomib.