Markedly lowering the viscosity of aqueous solutions of DNA by additives

作者：Elkin Igor; Weight Alisha K; Klibanov Alexander M^*

来源：International Journal of Pharmaceutics, 2015, 494(1): 66-72.

DOI：10.1016/j.ijpharm.2015.08.019

• DNA aqueous solutions
• Viscosity-lowering additives
• Local anesthetics
• Double-stranded DNA denaturation

Aqueous solutions of DNAs, while relevant in drug delivery and as a target of therapies, are often very viscous making them difficult to use. Since less viscous solutions could enable targeted drug delivery and/or therapies, the purpose of the present work was to explore compounds capable of "thinning" such DNA solutions under pharmaceutically relevant conditions. To this end, viscosities of aqueous solutions of DNAs and model polyanions were examined at 25 degrees C in the absence and presence of a number of bulky organic salts (and related compounds) previously found to substantially lower the viscosities of concentrated protein solutions. Out of two dozen compounds tested, only three were found to be effective; the FDA-approved local anesthetics lidocaine, mepivacaine, and prilocaine at near-isotonic concentrations and pH 6.4 lowered solution viscosity of three different DNAs up to about 20 fold. The observed multi-fold viscosity reductions appear to be due to these bulky organic salts' structure-specific non-covalent binding to nucleotide bases resulting in denaturation (unwinding) to, and stabilization of, single-stranded DNA.

• 出版日期2015-10-15
• 单位MIT