A novel controlled release tetrandrine-loaded PDLLA film: evaluation of drug release and anti-adhesion effects in vitro and in vivo

Hai Yao,Zhilong Deng,Lei Peng,Jian Liu,Xiaoxing Zhang,Zhidong Cao

doi:10.1007/s13346-019-00654-x

Abstract

To investigate the drug release and anti-adhesion effects of a TET (tetrandrine)-loaded PDLLA (poly-dl-lactide) film. Detection of TET release in vitro was carried out by high-performance liquid chromatography (HPLC) every 2 days following immersion of the tetrandrine-loaded PDLLA film in simulated body fluid until the TET content of the eluate could not be detected. For the in vivo test, TET-loaded PDLLA films were implanted into animal laminectomy models and positive and blank control groups were also set up. Postoperative serum tests, and macroscopic and histological analyses at 1, 4, 8, and 12 weeks, were used to assess the effects of the film. Statistical analyses were performed by one-way ANOVA. The drug release of the tetrandrine-loaded PDLLA film in vitro showed two phases with a second release peak. Ultimately, the duration of continuous delivery was up to 66 days and the cumulative delivery rate was up to 93.18%. Scores for the proliferation of epidural scars or adhesion of the dura mater in the test group were much lower than those for the two control groups. Histological analysis revealed the test group had fewer inflammatory cells and fibroblasts, as well as fewer extracellular collagen fibers, and a lower histology score than those of the two control groups at all time points. Tetrandrine-loaded PDLLA film is a novel controlled drug release and anti-adhesion material in vitro and in vivo.

Highlights

Failed back surgery syndrome (FBSS) is a cluster of symptoms following spine surgery, which is characterized by persistent, chronic, or recurrent pain in the back or limbs after laminectomy [1]
Extension of epidural fibrosis into the neural canal and adhesion to the dura mater are among the main causes of FBSS—accounting for up to 24% of all cases—and can lead to chronic nerve radicular pain and lower extremity weakness post-laminectomy [2]
Biodegradable polymeric materials have been shown to significantly reduce epidural fibrosis, the process of re-absorption resulted in a fibrotic mass and a gap forming between the sheet and the dura [13]

Summary

Introduction

Failed back surgery syndrome (FBSS) is a cluster of symptoms following spine surgery, which is characterized by persistent, chronic, or recurrent pain in the back or limbs after laminectomy [1]. Extension of epidural fibrosis into the neural canal and adhesion to the dura mater are among the main causes of FBSS—accounting for up to 24% of all cases—and can lead to chronic nerve radicular pain and lower extremity weakness post-laminectomy [2]. Because of the presence of fibrotic tissue and adhesion at the original surgery site during revision procedures, there is a higher risk of iatrogenic complications such as dural tears, nerve root injury, instability, and adhesion recurrence [3]. The use of biodegradable polymeric materials to impede epidural fibrosis adhesion is attracting significant theoretical and practical interest [11]. Biodegradable polymeric materials have been shown to significantly reduce epidural fibrosis, the process of re-absorption resulted in a fibrotic mass and a gap forming between the sheet and the dura [13]. DLLA alone was unable to prevent nerve root adhesion

Methods

Results

Conclusion