Smart drug delivery system activated by specific biomolecules.

Essentially, the human body can release in different disease conditions specific biomolecules such as histamines when the body encounters a toxic substance, antibodies which are part of the body's natural immune response or nitric oxide as a cardiovascular signalling molecule. Design and development of "intelligent" delivery systems able to release the therapeutic agent only in the presence of bioactive compounds was presented here. Poly(N-isopropylacrylamide-co-N-(3-aminopropyl)methacrylamide)) (poly(NIPAAm-co-APM)) was synthesized as an exciting pH/temperature sensitive copolymer. Under physiological conditions (pH = 7.4), the APM in copolymer is in the ionized state (pKa = 8.7), highly hydrophilic and therefore the copolymer loses thermosensitive properties. Remarkably, after electrostatic interactions of APM with specific biomolecules, the copolymer restores the thermosensitive property. Thus, the microgels synthesized from this copolymer are in the "inactivated" state at normal physiological pH and temperature (pH = 7.4 and T = 36 °C). In the presence of specific biomolecules, microgels undergo "activation", shrink and expel mechanically a certain amount of drug. It must be mentioned that the pH-sensitive component plays the role of a biosensor, the biomolecule acts as a triggering agent, and the poly(NIPAAm) represents the delivery component (actuator). MTT tests showed that poly(NIPAAm-co-APM) microspheres are completely devoid of toxicity; moreover, the rabbit dermal fibroblasts vastly adhere to the surface of microspheres.