Synthesis of core-crosslinked zwitterionic polymer nano aggregates and pH/Redox responsiveness in drug controlled release.

A new kind of core-crosslinked zwitterionic polymer nano aggregates was prepared by two steps: (1) terpolymers of lipoic acid, polyethylene glycol diglycidyl ether and l-lysine were prepared, forming nano aggregates with hydrodynamic radius of 80 nm-183 nm by self-assembly; (2) the crosslinking of the nano aggregates took place through a reaction of side chain group in lipoic acid structural unit with 1,4-dimercaptothreotol, producing zwitterionic polymer core-crosslinked nano aggregates. The aggregates were stable against dilution and protein adsorption, and they demonstrated good pH/redox dual-responsiveness due to the introduction of disulfide bonds and zwitterionic groups to the nano aggregates. Doxorubicin (DOX) was loaded into the nano aggregates for controlled release. The drug-loaded nano aggregates exhibited obvious pH and reduction sensitivities in response to the environmental conditions in tumor cells. The nano aggregates were biocompatible and could be potentially applied as anticancer drug vehicles for enhancement of cellular uptake of anticancer drugs.

Preparation and controlled drug release ability of the poly[N-isopropylacryamide-co-allyl poly(ethylene glycol)]-b-poly(γ-benzyl-l-glutamate) polymeric micelles.

The polymeric micelles were prepared through a copolymerization of allyl polyethylene glycol (APEG) and N-isopropylacrylamide in the presence of 2-aminoethanethiol (AET), followed by a ring opening polymerization of γ-benzyl-l-glutamate N-carboxyanhydride (BLG-NCA). Doxorubicin (DOX) as a model drug was covalently conjugated into the core of micelles via hydrazone bonds. The drug loading capacity could reach up to 15% with drug encapsulation efficiency of 80%. The pH/thermo sensitivities were observed in the process of in vitro drug release. The DOX-loaded micelles exhibited accelerated drug release behaviors in an acidic condition, and enhanced therapeutic efficacy was observed. Furthermore, the cytotoxicity of micelles against Hela and 3T3 cells was evaluated before and after drug loading. The DOX-loaded micelles showed strong cytotoxic activity to the cancer cells. But the blank micelles showed non-cytotoxicity. Therefore, the thermo/pH dual-responsive polymeric micelles have a promising future applied as a controlled drug delivery system for anticancer drugs.

Thermo- and pH-sensitive ionic-crosslinked hollow spheres from chitosan-based graft copolymer for 5-fluorouracil release.

Thermo- and pH-sensitive ionic-crosslinked hollow spheres from self-assembly of chitosan-graft-poly(N-isopropylacrylamide) (CS-g-PNIPAM) for controlled release of 5-fluorouracil were studied. CS-g-PNIPAM aggregated into core-shell micelles with collapsed PNIPAM as the core and CS as the shell at the temperature above LCST. Ionic crosslinking reagent sodium tripolyphosphate (TPP) was used to crosslink the shell to form hollow spheres after cooling to room temperature. The size of hollow spheres was manipulated by changing pH or temperature of the environment. The CS-g-PNIPAM hollow spheres with plenty of inner cavities showed high loading capacity for 5-fluorouracil due to the polymer-drug interactions. Release of 5-fluorouracil from nanoparticles was accelerated at the temperature above LCST ascribed to the destruction of polymer-drug interactions and the decrease of particles size. Changing pH or ionic strength deformed the structure hollow spheres, which led to the increase of drug release. These hollow nanoparticles with environmentally sensitive properties are expected to be utilized in the field of intelligent drug delivery.