Fast-responsive porous thermoresponsive microspheres for controlled delivery of macromolecules

Porous thermoresponsive microspheres with a homogeneous dimension and distribution of the pores are synthesized by an original method. Poly(N-isopropylacrylamide-co-acrylamide) (poly(NIPAAm-co-AAm)) copolymer was obtained as a thermoresponsive material with a lower critical solution temperature (LCST) under physiologic-like conditions (i.e., at 37 °C and pH 7.4, 50 mM phosphate buffer). Semitelechelic oligomers of NIPAAm (ONIPAAm) were also synthesized in the presence of 3-mercaptopropionic acid (MPA) (chain transfer molecule) which acts as a pore-forming agent. Poly(NIPAAm-co-AAm) and ONIPAAm were solubilized in acidified aqueous solution, dispersed in a mineral oil, and transformed in stable microspheres by crosslinking the amide group with glutaraldehyde at temperatures below and above the LCST of the oligomers, and always below the LCST of the polymer. Microspheres obtained at temperatures below the LCST of ONIPAAm are characterized by a homogeneous porous structure with a narrow distribution of the pore size. These microspheres are characterized by a very rapid response rate when the temperature changes below and above the body temperature. The higher is the amount of the porogen in the polymer solution, the larger is the pore size and faster is the response rate. The porous microspheres with suitable pore size are a conveyable matrix for loading and temperature-controlled release of the high molecular weight model drug blue dextran (BD).