Drug release characteristics of physically cross‐linked thermosensitive poly(N‐vinylcaprolactam) hydrogel particles

The effect of physical cross‐linking was studied on the formation and properties of thermosensitive polymer particles of poly(N‐vinylcaprolactam), PVCL, and PVCL grafted with poly(ethylene oxide) macromonomer, PVCL‐graft‐C11EO42. Loading and release of model drugs into/from the hydrogel particles were evaluated. Thermosensitive particles were stabilized by cross‐linkers, the most feasible of which was salicylic acid (SA). At 23°C, below the lower critical solution temperature (LCST) of the thermosensitive polymers, stability of the hydrogels was poor, whereas at 37°C stable hydrogel particles were formed. All the drugs and also the cross‐linker (SA) were released more efficiently from the PVCL particles compared to the PVCL‐graft‐C11EO42 particles. Drug concentration and pH affected clearly the rate and extent of drug release in physiological buffer. The higher drug release from the PVCL was based on the more open gel‐like structure as opposed to PVCL‐graft‐C11EO42 particles. Complex formation between the cross‐linker and the polymers was due to the hydrogen bonding between the hydroxyl groups of SA and H‐bond acceptors of the PVCL. In the case of PVCL‐graft‐C11EO42, the ethylene oxide chain provided more opportunities for H‐bonding in comparison to the pure PVCL, creating more stable complexes (more tightly packed particles) leading to sustained drug release.