Design Of Stimuli-Responsive Bilock Copolymer-Ased Drug Delivery System And Its Application

The use of polymeric micelle in drug delivery has become prominent because of their biodegradability,designability,and biocompatibility.However,the application of polymeric micelles faces great challenges due to the insufficient function of hydrophobic chain,especially in drug delivery.Looking back over the advancement of polymeric micelles in drug delivery,it bring our awareness that hydrophobic chain is only used to encapsulate active drug without other functions.One approach involves the use of hydrophobic chain with versatility.Accordingly,two drug delivery systems based on block copolymner were designed and further explore their application in cancer treatment.The specific study are as follows:Firstly,the polymer-doxorubicin conjugates are synthesized from hydrophilic copolymer and hydrophobic chain composed of doxorubicin(DOX).DOX,a common hydrophobic anticancer drag,is used to serve as a hydrophobic chain for inducing selfassembly of polymer-doxorubicin conjugates.The self-assembly of polymerdoxorubicin conjugates facilitates the encapsulation of unreacted doxorubicin to form DOX-loaded polyprodrug micelles that possess a low CMC in aqueous solution,which improves the use efficiency of expensive DOX.The detachment of DOX moieties from polymer-doxorubicin conjugates caused by amidase facilitates the disintegration of DOX-loaded polyprodrug micelles to trigger the enhanced release of DOX in a slightly acidic medium.It is demonstrated that the DOX-loaded polyprodrug micelles have a higher suppression against cancer cells in in vitro investigations.This work thus proposes a strategy to modify the poor functionality of polymer-based nanostructures,through designing the medicated hydrophobic chains.This strategy facilitates the potential application of polymer-drug conjugates and provides profound insights into the effect of medicated polymer on drug delivery system.Secondly,in this work,we further advance the field by synthesizing new polymeric nanoparticles which can release a cancer drug(doxorubicin(DOX))in response to tumor microenvironment.This was achieved by efficiently coupling a N(3-Aminopropyl)-imidazole(Imi)moiety onto poly(acrylic acid)(PAA).The coordination between the Imi moiety and zinc ion induces the self-assembly of the resulting copolymers into polymeric nanoparticles via a coordination-induced selfassembly mechanism.Upon exposure of the polymeric nanoparticles to slightly acidic condition,which can destroy the coordination bond between the Imi side chain and the zinc ion.The pH-responsive property turns the polymeric nanoparticles back to the water-soluble copolymers and therefore,disassembles the nanoparticles and also releases the as-loaded DOX.In vivo results further confirm that the polymeric nanoparticles possesses toxicity to tumor cells.Accordingly,this new copolymer is very promising for drug delivery applications,especially when using the water as solvent is essential.