Yan Lin1, Yujie Wan1, Xingjie Du1, Jian Li1, Jun Wei1, Ting Li1, Chunhong Li1, Zhongbing Liu1, Meiling Zhou2, Zhirong Zhong3. 1. Department of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical University, Luzhou, 646000, Sichuan, China. 2. Department of Pharmacy, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China. meilzhou@163.com. 3. Department of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical University, Luzhou, 646000, Sichuan, China. zhongzhirong@126.com.
Abstract
BACKGROUND: Spinal 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). RESULTS: The 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. CONCLUSIONS: The target drug delivery system can overcome the defect of low solubility of TMP, achieve the targeting ability, and show the further clinical application prospect.
BACKGROUND:Spinal 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). RESULTS: The 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. CONCLUSIONS: The target drug delivery system can overcome the defect of low solubility of TMP, achieve the targeting ability, and show the further clinical application prospect.
Entities:
Keywords:
Human serum albumin; Nanoparticles; Pharmacokinetics; Spinal cord injury; Tetramethylpyrazine