Limiting the level of tertiary amines on polyamines leads to biocompatible nucleic acid vectors.

Autor: Simão Carlos MI; School of Pharmacy, University College London, 29-39 Brunswick Square, London, WC1N 1AX, UK., Zheng K; School of Pharmacy, University College London, 29-39 Brunswick Square, London, WC1N 1AX, UK; School of Chemical Engineering and Environment, Beijing Institute of Technology, 5 South, Zhongguancun Street, Beijing, 100081, PR China., Garrett N; School of Physics, University of Exeter, Stocker Road, Exeter, EX4 4QL, UK., Arifin N; School of Pharmacy, University College London, 29-39 Brunswick Square, London, WC1N 1AX, UK., Workman DG; School of Pharmacy, University College London, 29-39 Brunswick Square, London, WC1N 1AX, UK., Kubajewska I; School of Pharmacy, University College London, 29-39 Brunswick Square, London, WC1N 1AX, UK., Halwani AA; School of Pharmacy, University College London, 29-39 Brunswick Square, London, WC1N 1AX, UK; School of Pharmacy, King Abdulaziz University, Abdullah Sulayman St., Jeddah, 80200, Saudi Arabia., Moger J; School of Physics, University of Exeter, Stocker Road, Exeter, EX4 4QL, UK., Zhang Q; School of Chemical Engineering and Environment, Beijing Institute of Technology, 5 South, Zhongguancun Street, Beijing, 100081, PR China., Schätzlein AG; School of Pharmacy, University College London, 29-39 Brunswick Square, London, WC1N 1AX, UK; Nanomerics Ltd, Euro House, 1394 High Road, London, N20 9YZ, UK., Uchegbu IF; School of Pharmacy, University College London, 29-39 Brunswick Square, London, WC1N 1AX, UK; Nanomerics Ltd, Euro House, 1394 High Road, London, N20 9YZ, UK. Electronic address: ijeoma.uchegbu@ucl.ac.uk.
Jazyk: angličtina
Zdroj: International journal of pharmaceutics [Int J Pharm] 2017 Jun 30; Vol. 526 (1-2), pp. 106-124. Date of Electronic Publication: 2017 Apr 25.
DOI: 10.1016/j.ijpharm.2017.04.059
Abstrakt: 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 (DS tert ) was inversely proportional to the IC50 of the EAGC polymers in the A431 cell line: IC50=6.18DS tert -0.9 , r 2 =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.
(Copyright © 2017 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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