Controlled Nitric Oxide Delivery Platform Based onS-Nitrosothiol Conjugated Interpolymer Complexes for Diabetic Wound Healing
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Abstract
Nitric oxide (NO) is known to play a critical role in enhancing wound healing as topical NO administration has demonstrated enhanced wound healing in diabetic animal models. However, this approach has been limited by the short duration of NO release, short half-life of NO, and instability of available NO donors. To overcome these deficiencies, we have developed a new NO delivery platform based on grafting S-nitrosothiols (RSNOs), derived from endogenous glutathione (GSH) or its oligomeric derivatives, phytochelatins (PCs), onto poly(vinyl methyl ether-co-maleic anhydride) (PVMMA), and their subsequent formation of interpolymer complexes with poly(vinyl pyrrolidone) (PVP). Such interpolymer complexes provide controlled release of NO for an extended duration (>10 days) and exhibit enhanced stability in the solid state over that of free RSNOs. The existence of intermolecular hydrogen bonding in such complexes and the formation of disulfide bonds following the NO release have been confirmed by FTIR and Raman. Preliminary wound healing study in a diabetic rat model demonstrates that, with a single topical application, the present controlled release NO delivery system can effectively accelerate wound closure as compared with the control (p < 0.05). The results suggest that the present NO releasing interpolymer complexes could be potentially useful for diabetic wound healing.
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