Journal
ACS APPLIED POLYMER MATERIALS
Volume 2, Issue 5, Pages 2027-2034Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsapm.0c00203
Keywords
anti-inflammatory; nitric oxide; dendrimer; drug delivery; nanomedicine; nanoparticles
Funding
- Sao Paulo Research Foundation (FAPESP) [2015/23761-2, 2018/02093-0, 2018/14142-5, 2016/02414-5, 2015/04929-0]
- National Council for Scientific and Technological Development (CNPq) [307403/2018-1]
- Coordination for the Improvement of Higher Education PersonnelCAPES
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior -Brasil (CAPES) [001]
- Coordination for the Improvement of Higher Education PersonnelCAPES (CAPES/DAAD Co-financed Short-Term Research Grant Brazil, 2018) [57417991, 91674518]
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [15/23761-2] Funding Source: FAPESP
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Inflammatory processes are related to a wide variety of diseases with high global impact. Nitric oxide (NO) is an excellent candidate for the treatment of such diseases due to its important anti-inflammatory role in living systems, which is related to its concentration in the cellular medium that in turn depends directly on its release rate from NO releasing compounds. In this work, we synthesized a nitrate-terminated dendrimer and evaluated its anti-inflammatory properties. Remarkably, dendrimer bearing 18 NO-releasing groups was nontoxic, and exhibited anti-inflammatory activity (13.7-27.9% of IL-8 inhibition) throughout the tested concentrations (6.50 X 10(-2) to 4.17 X 10(3) nM of dendrimer; (1.17-7 SO x 10(4) nM of NO-moiety) On the other hand, the NO-releasing monomer was pro-inflammatory at concentrations higher than 62.5 nM. Investigation of the NO-releasing profiles from monomer and dendrimer using real-time NO analyzer NOA confirmed the slow release of NO from the dendrimer. Our results suggest that the NO release from the dendrimer occurs in a controlled fashion, keeping the anti-inflammatory effect of NO even at high concentrations.
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