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

Abstract

The copolymers of N-isopropyl acrylamide (NIPA) have been studied extensively as drug carriers for antibacterial, cardiovascular, cytostatic, local anesthetic, and nonsteroidal anti-inflammatory agents, to deliver the required therapeutic effect. The aim of this work was to evaluate the effect of a series of newly synthesized thermosensitive polymeric NIPA derivatives on the release rate of naproxen sodium (NS) from hydrogels composed of hydroxypropyl methylcellulose (HPMC). NIPA derivatives P1–P4 were synthesized by precipitation polymerization without an emulsifier, and their structures were evaluated by NMR spectroscopy. Four formulations were prepared with NS (FP1–FP4), and rate of NS release from these systems was evaluated using a modified pharmacopeial method at 22 and 42 °C. The release rate of NS followed a similar trend in all four of the formulations assessed at 22 °C, which was the same as the reference formulation. However, the release rate of NS at 42 °C was clearly faster in the samples containing the thermosensitive polymers P1–P4 compared with the reference formulation. These results clearly demonstrate that the use of thermosensitive polymeric derivatives of NIPA can increase the release rate of NS from hydrophilic gels based on HPMC. Diversity of release courses of naproxen sodium evaluated in formulation containing poly(ethylene glycol) dimethacrylate (PDA, left), and comparison of half-release times (THR, right) of naproxen sodium formulations containing various thermosensitive polymers P1–P4.