Abstract
Poly(L-lactic acid) (PLLA) matrix systems incorporated with poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) containing nitric oxide (NO) donors (DETA NONOate) were developed for prevention of heart valve complications through sustained and controlled release of NO. PLLA matrices were prepared using the salt leaching method and the properties and drug release profiles were characterized. For assessment of the effects of PLLA systems on the pharmacological responses and cytotoxicity, various factors, such as calcium content, alkaline phosphatase (ALP) activity, cyclic guanosine monophosphate (cGMP) expression, intercellular adhesion molecule (ICAM-1) expression and cell viability of porcine aortic valve interstitial cells (PAVICs), were evaluated. PLLA matrices embedded with PLGA- NPs demonstrated its usefulness in alleviating the calcification rate of the VICs. The cGMP levels under osteoblastic conditions significantly increased, supporting that anticalcification activity of NO is mediated through NO-cGMP signaling pathway. The level of ICAM-1 expression in cells exposed to NO was lowered, suggesting that NO has an inhibitory activity against tissue inflammation. NO releases from PLLA matrix embedded with PLGA NPs prevented valvular calcification and inflammation without causing any cytotoxic activities. PLLA matrix system loaded with NPs containing NO donors could provide a new platform for sustained and controlled delivery of NO, significantly reducing valvular complications.
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