Chitosan functionalized thermosponge nano-carriers for prolonged retention and local delivery of chymopapain at the nucleus pulposus in porcine discs ex vivo

Abstract

Injection of chymopapain, a proteolytic enzyme, has been used in clinics for the treatment of spinal disc herniation, which is the major cause of lower back pain. However, the fast and wide diffusion and spreading of the enzyme from the injection site limit its effect and could cause severe side effects. Pluronic based nano-carriers were employed for the localized delivery of chymopapain and characterized in a porcine disc ex vivo as well as in vitro. Bare and chitosan conjugated thermosponge nano-carriers were prepared by photo-crosslinking either diacrylated Pluronic F127 or diacrylated Pluronic F68. Chymopapain was efficiently loaded into the nano-carriers with an encapsulation efficiency of over 95% in all the nano-carriers. In vitro release studies in physiological conditions (pH 7.4, 37 degrees C) showed a sustained release of the enzyme from all the nano-carriers but release from chitosan modified nano-carriers (similar to 16 days) was slower than that from the bare nano-carriers (similar to 12 days). Chymopapain delivered by nano-carriers remained more localized at the injection site in the nucleus pulposus of ex vivo porcine discs, compared to free chymopapain. Chitosan functionalized nano-carriers showed longer retention and slower diffusion of the enzyme compared to bare nano-carriers. The results suggest the potential use of the nano-carrier for the local delivery of chymopapain at the nucleus pulposus in discs.