The Zhejiang University team has developed a new polymer micelle, which is expected to treat intervertebral disc degeneration

Intervertebral disc degeneration (IVDD) is the main cause of people's low back pain, which may cause high medical expenses

In order to solve these treatment problems, researchers at Zhejiang University have designed a new type of amphiphilic polymer micelle based on apocynin (APO), in which the core of the micelle contains the small molecule compound kartogenin (KGN), Used for the treatment of intervertebral disc degeneration

Researchers have found that this polymer micelle can accurately and controllably deliver APO and KGN.

Design and synthesis of PAKM

In order to develop a drug delivery system based on polymer micelles, researchers first connect APO drugs to polymer chains through esterase-responsive phenolic ester bonds, and encapsulate KGN in the core of the micelles to form a single complex PAKM

PAKM is an injectable polymer micelle that can achieve controlled release of APO and KGN

Bioactivity of PAKM

Next, the researchers evaluated the effect of De-PAKM (PAKM degradation product obtained by esterase) on cell viability

When the intervertebral disc degenerates, the water content of the annulus fibrosus and nucleus pulposus gradually decreases, the height of the intervertebral disc decreases, the nucleus pulposus cells (NP) decrease, and the extracellular matrix (ECM) degrades

Later, they also used the DCFH-DA probe to evaluate the intracellular ROS production induced by H2O2

In addition, PAKM also has a strong ability to inhibit ECM degradation and induce human ADSCs to differentiate into nucleus pulposus

Autophagy plays a vital role in maintaining the homeostasis of stem cells and can help cells resist excessive oxidative stress in the degeneration of intervertebral discs

In vivo therapeutic effects of PAKM

Finally, the researchers evaluated the height of the intervertebral disc through X-ray analysis to evaluate the in vivo treatment effect of PAKM; and evaluated the water content of the intervertebral disc through magnetic resonance imaging (MRI)

Concluding remarks

In summary, researchers have developed an injectable esterase-responsive micelle PAKM that delivers APO and KGN to the intervertebral disc

Original Search

Yu C, Li D, Wang C, et al.