Synthesis, evaluation and release studies of NIPA nanopolymers presumed for temperature-controlled drug delivery

Research toward the development of targeted and controlled drug delivery systems capable of carrying therapeutic agents to their required site of action has grown considerably during the last decade, because these systems offer a potential reduction in off-target effects. A variety of different methods have been evaluated to date for the preparation of specific polymeric drug carriers, including both bottom-down and bottom-up methods such as surfactant-free precipitation polymerization, surfactant-free emulsion polymerization and electrospinning [ 1 , 2 ]. N -Isopropyl acrylamide (NIPA) is an interesting monomer that has been applied extensively as a research tool for the development of new polymeric drug carriers [ 3 ]. The popularity of this material in scientific research can be attributed to the unique features of poly-NIPA (pNIPA) particles, which exhibit a sharp and reversible volume phase transition at a volume phase transition temperature (VPTT) of 32 °C [ 4 – 6 ]. The temperature of this process is especially important because it corresponds well with the range of normal human and animal body temperatures [ 7 , 8 ]. At temperatures below the VPTT, these macromolecules become swollen when they are mixed with water. In contrast, at temperatures above their VPTT, these particles become hydrophobic and form compact structure, resulting in the dehydration of the material [ 9 , 10 ]. The synthesis of polymeric NIPA derivatives with comonomers uses an initiator, and the particles prepared in this way may be stabilized by sulfate groups derived from the persulfate ion of the attached initiator molecule [ 11 ]. It is noteworthy that a wide variety of structures may be formed during the synthesis of pNIPA macromolecules [ 12 ]. A diverse range of comonomers has been applied to the synthesis of NIPA derivatives, including acrylic acid [ 13 ], methacrylic acid [ 14 ], fumaric acid [ 14 ], acryl amide [ 15 ], maleic acid [ 16 ] and N - t -butyl acryl amide [ 17 , 18 ]. The copolymers of NIPA have been studied extensively as drug carriers for antibacterial, cardiovascular, cytostatic, local anesthetic and nonsteroidal anti-inflammatory agents, to obtain the required therapeutic effect [ 19 ]. Although NIPA derivatives are widely recognized as potential drug carriers and nanocarriers, their practical application has been limited by their poor biodegradability. NIPA derivatives have been used effectively in the field of topical medicine, as exemplified by their use in several other studies [ 20 – 22 ].