(a) Panoramic view. (b) Isolated magnified particle. Reprinted from Oliveira et al. [6], with the permission of Editorial Executive, Research … Polymeric micelles are generally lower in size than nanoparticles and liposomes and larger than dendrimers, while sufficiently small (less than 100nm in diameter) to penetrate tissues. Additionally, liposomes can be eventually dissembled after all drug has been delivered [63]. Inhibitors,research,lifescience,medical A small number of reports have been published
on the delivery of NO using polymeric systems. Oliveira et al. [6] developed and characterized PLGA nanoparticles containing the NO donor agent (trans-[RuCl([15]ane)(NO)]2+). One year later, Jain et al. [71] demonstrated that then stabilization of NO pro-drugs and anticancer lead compounds via their incorporation into polymer-protected nanoparticles composed of polystyrene-b-PEG (PS-b-PEG) and PLA-b-PEG may enhance their therapeutic effects. Meanwhile, Yoo et al. [72] described PLGA microparticles containing an NO donor that efficiently delivered NO to the vaginal mucosa, Inhibitors,research,lifescience,medical resulting in improved vaginal blood perfusion, which may have implications in the treatment of female sexual dysfunction. Another potential clinical application of polymeric nanocarriers is in sellectchem topical NO delivery, such as by incorporation of NO donors into a liquid PEG/water matrix [31]. Finally, Inhibitors,research,lifescience,medical Kanayama
et al. [66] reported that PEGylated polymer micelles may be capable of delivering exogenous NO to tumor cells in a photocontrolled manner, resulting in an
NO-mediated antitumor effect, which indicates the promise of this polymeric system in NO-based tumor therapy. 2.2. Dendrimers and Hydrogels Dendrimers are monodisperse macromolecules with a tridimensional Inhibitors,research,lifescience,medical structure that is highly ramificated and regular Inhibitors,research,lifescience,medical around the nucleus [64, 73]. The ability to store NO on a dendritic scaffold using the NO donor N-diazeniumdiolate was first demonstrated by Stasko and Schoenfisch [74]. Benini et al. [75] then reported that the system formed by anchoring of K[RuIII(edta)(Cl)] to poly(amidoamine) dendrimers (PAMAM) can relax aortic rings lacking endothelium and exert trypanocidal effects. Meanwhile, Stasko et al. [76] synthesized two generation-4 PAMAM dendrimers with S-nitrosothiol exteriors (Figure 2) and characterized their Drug_discovery ability to inhibit thrombin-mediated platelet aggregation. Figure 2 Generation-4 PAMAM with a completely modified exterior (64 thiols) of S-nitroso-N-acetyl-D,L-penicillamine (G4-SNAP) or S-nitroso-N-acetylcysteine (G4-NACysNO). Reprinted from Stasko et al. [76], with the permission of American Chemical Society, ACS Publications. … Another interesting delivery system is hydrogel (Figure 3), a three-dimensional hydrophilic polymeric network that can absorb and retain a considerable amount of water while maintaining shape. This system has enormous potential in the design of closed-loop drug delivery.