Negative Thermo-responsive Microspheres Based on Hydrolyzed Gelatin as Drug Delivery Device

This paper deals with the synthesis of thermo-responsive microspheres with proteic structure exhibiting a transition temperature close to the body temperature. Temperature-sensitive hydrogels have attracted extensive interest due to their potential and promising applications in drug delivery field since they can undergo a rapid and reversible phase transition from a swollen to a shrunken state depending on environmental temperature. The hydrogels were synthesized by free-radical polymerization of hydrolyzed methacrylated gelatin (HGel-MA) and N,N'-methylenebisacrylamide as pro-hydrophilic multifunctional macromer and crosslinker, respectively, and N-isopropylacrylamide as thermo-responsive monomer. Thermal analyses showed negative thermo-responsive behavior for all compositions and, by increasing the content of the hydrophilic moieties in the network, the transition temperature raised to 36.9A degrees C, close to the physiological values. In order to test the materials as drug carriers, diclofenac sodium salt was chosen as model drug. Drug release profiles, in phosphate buffer solution (pH 7.0, 10(-3) M) at 25 and 40A degrees C, depend on the hydrogel's crosslinking degree and hydrophilic/hydrophobic balance in the polymeric network. For all formulations, in the shrunken state, the drug release percent values ranged from 80% to 100% after 24 h, and after 3 h, more than 60% of therapeutics was delivered. On the contrary, the swelling of the loaded microparticles produces, even after 30 h, a drug release percent of about 75%. By using semi-empirical equations, the release mechanism was extensively studied and the diffusional contribute was evaluated. The physico-chemical characteristics of thermo-responsive materials confirm the applicability of the microspheres as drug delivery device.