Abstract
Nitric oxide (NO) is a therapeutic implicated for the treatment of diseases afflicting lymphatic tissues, which range from infectious and cardiovascular diseases to cancer. Existing technologies available for NO therapy, however, provide poor bioactivity within lymphatic tissues. In this work, we address this technology gap with a NO encapsulation and delivery strategy leveraging the formation of S-nitrosothiols on lymphatic-targeting pluronic-stabilized, poly(propylene sulfide)-core nanoparticles (SNO-NP). We evaluated in vivo the lymphatic versus systemic delivery of NO resulting from intradermal administration of SNO-NP benchmarked against a commonly used, commercially available small molecule S-nitrosothiol NO donor, examined signs of toxicity systemically as well as localized to the site of injection, and investigated SNO effects on lymphatic transport and NP uptake by lymph node (LN)-resident cells. Donation of NO from SNO-NP, which scaled in proportion to the total administered dose, enhanced LN accumulation by two orders of magnitude without substantially reducing lymphatic transport of NP or the viability and extent of NP uptake by LN-resident cells. Additionally, NO delivery by SNO-NP was accompanied by low-to-negligible NO accumulation in systemic tissues with no apparent inflammation. These results suggest the utility and selectivity of SNO-NP for the targeted treatment of NO-regulated diseases that afflict lymphatic tissues. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1463-1475, 2018.