SILDENAFIL-MIL-89 FORMULATION AS POTENTIAL DRUG DELIVERY SYSTEM IN PULMONARY ARTERIAL HYPERTENSION

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Pulmonary Arterial Hypertension (PAH) is an aggressive disease with poor prognosis, no available cure, and low survival rates. Currently, there are several classes of vasodilator drugs that are commonly used as treatment strategies for PAH including sildenafil, a phosphodiesterase type 5-inhibitor. Despite their clinical benefits, these therapies are hindered by their systemic side effects. This limitation could be overcome using controlled drug release with the potential for targeted drug delivery using a nanomedicine approach. In the current study, we have evaluated the use of a highly porous nano-sized preparation of iron-based metal-organic framework (MOF) commonly referred to as MIL-89 for loading with sildenafil. We have previously shown that MIL-89 is relatively non-toxic in a range of human cell types and well tolerated in vivo. Here, we report the use of a nano-formulation of MIL-89 (nanoMIL-89) as drug delivery for the phosphodiesterase type 5-inhibitor sildenafil. nanoMIL-89 was first prepared and then successfully loaded with sildenafil ([email protected]). [email protected] was shown to release sildenafil in a biphasic manner with an initial rapid release over 6 hours followed by a more sustained release over 72 hours. Finally, the vasodilator effect of [email protected] was measured over 8 hours using isolated mouse aorta. Consistent with drug release kinetics, Sil-nanoMIL-89 induced vasodilation after a lag phase of 3 hours. [email protected] is a promising nano-formulation prototype of sildenafil displaying delayed drug release and vasodilator activity. Further pharmacological assessment of [email protected] in animal models for PAH is now required and constitutes the subject of an ongoing investigation.