Liposomes have also been used as models for bilayer membranes in studies to explore the effect of different phospholipids on diazeniumdiolate reactivity. It was found that anionic liposomes increased the dissociation rate of NO from diazeniumdiolate [91]. This study
leads to a better understanding of the local environmental factors influencing NO donors’ reactivity, and, since negatively charged phospholipids are important components of membranes and pulmonary surfactants, it may help explain the success obtained in experiments using diazeniumdiolate as a pulmonary vasodilator [92]. In another study, it was shown that positively charged liposomes, Inhibitors,research,lifescience,medical derived from the synthetic surfactant DOTAP, increase the dissociation of O2-arylated diazeniumdiolate prodrugs catalysed by the enzyme glutathionetransferase, in a membrane model system [91]. This prodrug has been successfully used to target NO to acute myeloid leukemia cells on activation
by glutathione/glutathione Inhibitors,research,lifescience,medical S-transferase. [93–95]. A cationic liposome composed of DOTAP has been used to transfer the gene nitric oxide synthase (NOS) to vascular smooth cells, which indicates the BIBW2992 potential therapeutic relevance for this transfer system to treat cardiovascular diseases [96]. These studies surely give insight into the use of charged Inhibitors,research,lifescience,medical liposomes as a strategy to deliver NO in a site-specific way, which would make them clinically more relevant. Cationic liposomes could be used, for example, not only for gene transfer, but to deliver a nitric oxide donor to blood vessels, which could enable Inhibitors,research,lifescience,medical a more potent vasodilatation because of the ability of cationic liposomes to interact with endothelium cells via electrostatic interaction [97]. 3.2. Solid Lipid Nanoparticles
Solid lipid nanoparticles, composed of a lipid matrix Inhibitors,research,lifescience,medical stabilized by a surfactant, have great potential as drug-delivery systems due to their safety, high physical stability, and controlled release capability. Additionally, lipid carriers may enable the successful topical administration Cytidine deaminase of many drugs due to attachment to the skin surface, allowing lipid exchange between the outermost layers of the carriers [98–100]. Solid lipid nanoparticles (SLNs) were first introduced in the early 1990s, followed by the second-generation technology of nanostructured lipid carriers (NLCs), particles produced using a blend of solid and liquid lipids to increase drug loading [101]. [Ru(Terpy)(bdqi)NO](PF6)3, an NO donor nitrosyl ruthenium complex (NRC), has been bound to lipid carriers for topical administration. This system exhibited improved stability in the skin and NO release by visible light irradiation, with potential applications in the treatment of skin cancer [102].