Controlling Drug Release of Anti-inflammatory Molecules Through a pH-Sensitive, Bactericidal Polymer Matrix: Towards a Synergic and Combined Therapy

This study aimed to tune the release of non-steroidal, antiinflammatory and antimicrobial diclofenac sodium salt from a bactericidal, pH-sensitive polymer matrix in view of the development of a synergic and combined therapy. The polymer matrix was represented by A(BC)n linear or branched copolymers (n = 1, 2) synthesized by Atom Transfer Radical coPolymerization (ATRP). Manufactures were obtained and analysed in film form, using solvent casting technique. 2-(dimethylamino) ethyl methacrylate (DMAEMA), 2-(diethylamino) ethyl methacrylate (DEAEMA) and 2-(diisopropylamino) ethyl methacrylate (DIPAEMA) have been used as comonomer bearing the bactericidal amino-groups and to modulate the pH-sensitivity of the material. The electrolytic and structural factors of the amino-groups, juxtaposed with the copolymer structure, gave raise to different interactions with the negatively charged diclofenac and imparted a finer control on the drug release kinetics. Data evidenced that copolymers with DMAEMA released diclofenac faster than those with DEAEMA and DIPAEMA; thus, the lower was the amine Kb, the faster was the release. The correlation between copolymer structure and kinetic/equilibrium of the drug release was analysed and correlated with the Tg of copolymers when diclofenac was loaded.