TAT-modified serum albumin nanoparticles for sustained-release of tetramethylpyrazine and improved targeting to spinal cord injury

Yan Lin,Xingjie Du,Jun Wei,Meiling Zhou,Zhirong Zhong,Jian Li,Zhongbing Liu,Chunhong Li,Ting Li,Yujie Wan

doi:10.1186/s12951-020-00766-4

Abstract

BackgroundSpinal Cord injury (SCI) is a kind of severe traumatic disease. The inflammatory response is a significant feature after SCI. Tetramethylpyrazine (TMP), a perennial herb of umbelliferae, is an alkaloid extracted from ligustici. TMP can inhibit the production of nitric oxide and reduce the inflammatory response in peripheral tissues. It can be seen that the therapeutic effect of TMP on SCI is worthy of affirmation. TMP has defects such as short half-life and poor water-solubility. In addition, the commonly used dosage forms of TMP include tablets, dropping pills, injections, etc., and its tissue and organ targeting is still a difficult problem to solve. To improve the solubility and targeting of TMP, here, we developed a nanotechnology-based drug delivery system, TMP-loaded nanoparticles modified with HIV trans-activator of transcription (TAT-TMP-NPs).ResultsThe nanoparticles prepared in this study has integrated structure. The hemolysis rate of each group is less than 5%, indicating that the target drug delivery system has good safety. The results of in vivo pharmacokinetic studies show that TAT-TMP-NPs improves the bioavailability of TMP. The quantitative results of drug distribution in vivo show that TAT-TMP-NPs is more distributed in spinal cord tissue and had higher tissue targeting ability compared with other treatment groups.ConclusionsThe target drug delivery system can overcome the defect of low solubility of TMP, achieve the targeting ability, and show the further clinical application prospect.

Highlights

Spinal Cord Injury (SCI) is one of the most common disabled diseases in the world, which is devastating and destructive and it results in incomplete or complete loss of autonomic motor and sensory function [1]
Many studies have shown that TMP can down-regulate the nitric oxide production and inhibit inflammation in peripheral tissues, which is the key to promote the functional recovery of acute Spinal Cord injury (SCI) [11]
Preparation and characterization of human serum albumin (HSA) nanoparticles HSA nanoparticles are commonly prepared by the specialized nanotechnological techniques such as desolvation, emulsification, self-assembly, and nanotechnology [20]

Summary

Introduction

Spinal Cord Injury (SCI) is one of the most common disabled diseases in the world, which is devastating and destructive and it results in incomplete or complete loss of autonomic motor and sensory function [1]. Many studies have shown that TMP can down-regulate the nitric oxide production and inhibit inflammation in peripheral tissues, which is the key to promote the functional recovery of acute SCI [11]. To improve the bioavailability of TMP in vivo and enhance the targeting ability to SCI, the key method is to design a new drug delivery system by using modern pharmaceutical preparation technology. It is of great value and significance to SCI patients and society. To improve the solubility and targeting of TMP, here, we developed a nanotechnology-based drug delivery system, TMP-loaded nanoparticles modified with HIV trans-activator of transcription (TAT-TMP-NPs)

Methods

Results

Discussion

Conclusion