The physiological effects of niosomes on the human left intermammarian artery

Objective: The aim of this study is to investigate the endothelium-mediated and direct vascular physiological responses of niosomes, which are drug delivery systems composed of nonionic surfactants and cholesterol, on the human left internal mammary artery (LIMA). Identifying the potential effects that niosomes may have at the vascular level will increase the predictability of hemodynamic changes that may be caused by these systems when administered parenterally. Method: Increased LIMA samples after coronary bypass surgery were transported in a suitable environment, suspended in an organ bath 3-4 mm long, left for one hour under 2 g tension, and then examined in the organ bath system. Vascular rings were constricted with phenylephrine at a concentration of 10⁻⁶ M, and relaxation responses were evaluated with acetylcholine. Endothelial integrity was defined as a relaxation response of 60% or higher. Thus, intact and damaged endothelial groups were created. Niosomes based on sorbitan monostearate (Span60) and polyethylene glycol octadecyl ether (Brij72; HLB 4,90), prepared by the thin-film hydration method, were incubated with sorbitan monostearate (Span 60;) at different concentrations in endothelial and non-endothelial vessels. Then, relaxation mechanisms were tested using L-NAME, L-arginine, indomethacin, charybdotoxin, and apamin. ANOVA and Tukey post-hoc tests were used for statistical analysis. Results: In experiments using Span 60-based niosomes, no difference was observed in vascular relaxation and contraction responses. In the experimental group using Brij72-based niosomes, statistically significant relaxation responses were produced in vessels with intact endothelium. Since no effect on physiological vascular responses was observed with Span 60-based niosomes, experiments were continued with Brij72-based niosomes, which produced a relaxation response in vessels. Since the experiments were conducted with a single niosome, the Brij72-based niosome was simply referred to as a "niosome". It was observed that the relaxation responses in vessels with intact endothelium were altered through nitric oxide and endothelial-derived hyperpolarization mechanisms. Conclusion: Niosome (Brij72-based niosome) has caused significant physiological changes in both the endothelium and directly at the vascular level in LIMA vessels. These results indicate that drugs encapsulated in niosomes may have hemodynamic effects when administered systemically and provide important clues about a possible mechanism for side effects that may be observed during the use of delivery systems. Key words: Niosomes, nonionic surfactant vesicles, vascular physiology