Stable and degradable microgels linked with cystine for storing and environmentally triggered release of drugs

Environmentally sensitive, degradable microgels based on poly(N-isopropylacrylamide) (pNIPA) cross-linked with the diacryloyl derivative of cystine (BISS) were synthesized by applying surfactant-free emulsion polymerization. pNIPA contributed the sensitivity to temperature to the microgels and the cross-linker made them degradable and sensitive to pH. The morphology of the microgels was investigated by using scanning and transmission electron microscopies (SEM and TEM). The gels formed spherical particles with a narrow size distribution. The influence of temperature, pH and ionic strength on the swelling behavior and the stability of new microgels with various contents of BISS (0, 1 and 3%) were investigated by dynamic light scattering (DLS). It was found that microgels with 3% content of amino acid were highly stable over a wide range of investigated temperatures, pH values and ionic strengths, including the physiological conditions (pH = 7.4, IS = 0.15 M, and 37 °C). The reduction-induced degradation of these microgels by 0.01 M solution of dithiothreitol (DTT) or glutathione (GSH) was studied by means of SEM and TEM; the obtained micrographs showed the destruction of spherical microgel particles. The microgels containing 3% of BISS could be loaded with doxorubicin (DOX) by employing the electrostatic interactions between the DOX amine group and the ionized carboxyl group from BISS. A significant increase in the cumulative release of DOX was observed after changing pH from that characteristic to blood (∼7.4) to that existing in affected cells (∼5.0) and in the presence of GSH (C_GSH∼ 10 mM). The cytotoxicity tests proved that the obtained microgels are interesting as useful carriers in directed drug delivery systems.