Limiting the level of tertiary amines on polyamines leads to biocompatible nucleic acid vectors
Publication date: 30 June 2017 Source:International Journal of Pharmaceutics, Volume 526, Issues 1–2 Author(s): Margarida Isabel Simão Carlos, Kai Zheng, Natalie Garrett, Natrah Arifin, David G. Workman, Ilona Kubajewska, Abdulrahman A. Halwani, Julian Moger, Qi Zhang, Andreas G. Schätzlein, Ijeoma F. Uchegbu We have designed an efficient, synthetic nucleic acid vector, which is relatively non-toxic. [N-(2-ethylamino)-6-O-glycolchitosan – EAGC] polymers were 10–50 fold less toxic than Lipofectamine 2000, able to complex DNA, mRNA and siRNA into positively charged (zeta potential=+40 − 50mV), 50–450nm nanoparticles. The level of tertiary amine N-2-ethylamino substitution (DStert) was inversely proportional to the IC50 of the EAGC polymers in the A431 cell line: IC50=6.18DStert −0.9, r2 =0.9991. EAGC polyplexes were stable against a heparin challenge, able to protect the nucleic acids from nuclease degradation and achieve levels of transfection comparable to Lipofectamine 2000 formulations. The relative biocompatibility of the vector allowed 10 fold higher doses of DNA (1μg compared to 0.1μg per well with Lipofectamine 2000) and siRNA (10.7μg per well vs 1.3μg with Lipofectamine 2000) to be applied to cells, when compared to Lipofectamine 2000. Finally intranasal application of EAGC – siRNA complexes resulted in siRNA transfer to the neurons of the olfactory bulb. Graphical abstract
Chun Peng, Yan-Ling Wang
Øyvind Bruserud, Daniela-Elena Costea, Saila Laakso, Ben-Zion Garty, Eirik Mathisen, Antti Mäkitie, Outi Mäkitie, Eystein S. Husebye
Shirley Telles, Sachin K. Sharma, Niranjan Kala, Sushma Pal, Ram K. Gupta, Acharya Balkrishna
The government needs to take action to stop prescription drugs, including opioids and slimming tablets, being obtained from online pharmacies that can avoid regulation.
Yao-Xin Gao, Hao-Heng Yu, Chuan He, Ming Li, Dan-Dan Guo, Jun-Jiang Lian, Hai-Jie Yang, Mian Wang, Lei Wang, Zhi-Wei Feng, Bin-Feng Cheng
Xuan Xie, Jun Jiang, Wenchu Ye, Ruohong Chen, Yiqun Deng, Jikai Wen
Ning Li, Heng Zhou, Qizhu Tang
Gantumur Battogtokh, Yong-Yeon Cho, Joo Young Lee, Hye Suk Lee, Han Chang Kang
Juan F. Garc ía-Henares, Jose A. Moral-Munoz, Alejandro Salazar, Esperanza Del Pozo
Authors: Schaefer A, Lubos E, Pietzsch JB, Pietzsch M, Weber S, Blankenberg S, Reichenspurner H, Schäfer U, Conradi L Abstract AIMS: The German healthcare system was among the first to introduce transcatheter mitral valve repair (TMVR) in routine care. Objective of this study was to analyze adoption and utilization patterns and to estimate impact of TMVR availability on mitral valve (MV) procedure volumes in the first 8 years after commercialization. METHODS AND RESULTS: Procedure volumes were collected from German Federal Statistics Office databases for TMVR and mitral valve surgery (MVS) from 2008-2015. ...