Controllable Enzymatic Degradation For Nano Drug Delivery Carrier

Complex polymeric micelles with a PLA core and a mixed PEG/PNIPAM shellwere prepared by self-assembly of two block copolymers: poly(ethyleneglycol)-b-poly(lactic acid)(PEG-b-PLA) and poly(N-isopropylacrylamide)-b-poly(lactic acid)(PNIPAM-b-PLA). Using1H NMR spectroscopy and dynamic lightscattering, the micellization and the enzymatic degradation status were characterized.At25C, the PNIPAM block is hydrophilic and the PLA core is prone to theenzymatic degradation, resulting in the disassembly of the micelles. While increasingthe temperature to45C, the PNIPAM collapsed onto the PLA core, protecting thePLA core from the attack by the enzyme, and the micelles exhibits a resistance to theenzymatic degradation. Furthermore, the enzymatic degradation rate of the micellescan also be tuned by changing the ratio of PEG to PNIPAM. With increasing contentof PNIPAM, the conformation of the collapsed PNIPAM changes from patchydomains to a continuous and dense layer, and the enzyme accessibility to the PLAcore is changed.A complex micellar system with a biodegradable PLA core and a mixedPEG/PDPA shell which was prepared by self-assembly of poly(ethyleneglycol)-b-poly(lactic acid)(PEG-b-PLA) and poly(2-(diisopropylamino) ethylmethacrylate)-b-poly(lactic acid)(PDPA-b-PLA) in aqueous solution. Using1H NMRand DLS, the co-micellization of the two polymers and the enzymatic degradation ofthe micellar core were characterized. Thank to the pH-responsible property of PDPAblock, the enzymatic degradation of the complex micelle can be controlled by thechange of pH value. While pH is below5.5, the PDPA block is hydrophilic and thePLA core is prone to the enzymatic degradation, resulting in the disassembly of themicelles. While the pH is increased above5.5, the PDPA collapsed onto the PLA core,protecting the PLA core from the attack by the enzyme, and the micelles exhibits aresistance to the enzymatic degradation. The application of this kind of complexmicelle was demonstrated by the controlled release of Indometacin in the presense or absence of enzyme.