Heat-activated sustaining nitric oxide release from zwitterionic diazeniumdiolate loaded in thermo-sensitive liposomes.
Zwitterionic diazeniumdiolate, a nitric oxide precursor, was dissolved in basic buffer solution (pH=9.0) and encapsulated in thermo-sensitive liposomes composed of phospholipids of different sensitive temperatures. The basic intra-liposomal environment dramatically delayed spontaneous NO release. When the liposomes were placed in physiological buffer solution and temperatures were increased to the sensitive temperatures of the phospholipids' membranes, extra-liposomal protons started to influx to collapse the pH gradient and subsequently induce a significant NO release. Moreover, the presence of a stronger pH gradient when the liposomes were applied to a more acidic environment caused a higher proton influx driving force to trigger the influx of protons and, subsequently, NO release. In this work, we demonstrate that thermo-sensitive liposomes can be used to create a stable pH gradient in a nanoenvironment entrapping zwitterionic diazeniumdiolate for sustained and heat/acid-activated NO release.
Tai
Lin-Ai
LA
Center for Nanomedicine Research, National Health Research Institutes, Zhunan 350, Taiwan.
Wang
Yu-Chao
YC
Yang
Chung-Shi
CS
D001391:Azo Compounds / Q000737:chemistry* / Q000378:metabolism; D016503:Drug Delivery Systems; D006358:Hot Temperature; D006863:Hydrogen-Ion Concentration; D008081:Liposomes / Q000737:chemistry* / Q000378:metabolism; D009569:Nitric Oxide / Q000737:chemistry* / Q000493:pharmacokinetics; D020030:Nitric Oxide Donors / Q000737:chemistry* / Q000493:pharmacokinetics
D001391:Azo Compounds; D008081:Liposomes; D020030:Nitric Oxide Donors; C452539:diazeniumdiolate; D009569:Nitric Oxide