Synthesis and experimental study of a novel polymer/gene compound drug controlled release system for the treatment of erectile dysfunction
Liu, J.; Xue, W.-R.; Zhao, L.-L.; Qu, X.-Z.; Yang, Z.-Z.; Li, R.; Deng, S.-Z.; Xiao, F.; Hu, X.-P.; Bai, W.-J.
Zhonghua Nan Ke Xue 19(9): 771-775
2013
ISSN/ISBN: 1009-3591 PMID: 24386851 Document Number: 664456
To overcome the deficiency in the current therapies for erectile dysfunction (ED), we designed and synthesized a novel high-efficiency polymer/gene compound drug controlled release system and discussed the feasibility of pH and temperature dually sensitive injectable hydrogel in ED gene therapy. We synthesized optimal siRNA gene nanoparticles by characterizing the zeta potential of polylysine (PLL)/siRNA gene compounds, and established a pH and temperature dually sensitive injectable gene compound drug controlled release system via Schiffs reaction between glycol chitosan (GC) and benzaldehyde capped OHC-PEO-PPO-PEO-CHO. Then we demonstrated the sustained release of the system at different temperatures. When the mass ratio of PLL to siRNA was 20:1, the zeta potential of the PLL/siRNA gene compound reached the peak (+23.5 mV) and the siRNA was encapsulated by PLL in the maximal degree. GC and OHC-PEO-PPO-PEO-CHO was crosslinked via benzoicimine reaction when environmental pH was changed from 5.5 to 7.4. The reslease of the siRNA encapsulated in this system kept at a low rate at 37 degrees C, significantly enhanced with the increase of the temperature to 60 degrees C, rising to (122.5 +/- 5.3) microg at 1 000 minutes as compared with (23.8 +/- 6.0) microg at 37 degrees C (P < 0.05). The polymer/gene compound drug controlled release system was successfully synthesized, which improved the stability and capacity of gene carriers and achieved siRNA release at different temperatures, promising to be a new approach to the gene therapy of ED.