Effect of ultrasound on the stability of oligodeoxynucleotides in vitro

In order for oligodeoxynucleotides (ODNs) to be viable candidates for phonophoresis (i.e. ultrasound-enhanced delivery), they must remain stable on exposure to therapeutic ultrasonic waves. We have examined the stability of radiolabelled ODNs as a function of their chemistry (phosphodiester (PO) and phosphorothioate (PS)) and chain length (7-mer and 20-mer) in aqueous solutions at three different pH values (1, 2 and 7) when subjected to ultrasound at an intensity of 1.5 W cm⁻² for 30 min. Whereas all ODNs remained stable at pH 1, pH 2 or pH 7 in the absence of ultrasound, significant degradation was observed at pH 1 upon ultrasound treatment. The sensitivity of ultrasound-enhanced ODN degradation at this pH, starting with the most rapidly degradable species first, was 7-mer PO > 20-mer PO > 7-mer PS > 20-mer PS. Interestingly, ODN stability was unaffected by exposure to an equivalent heat-alone application (pH 1 at 44°C) thus indicating that the mechanical, rather than heating, effects of ultrasound are responsible for the observed ODN degradation.