Title : Metal-organic framework nanoparticles preparation of sildenafil: A new window in the treatment of pulmonary arterial hypertension
Background: Nanomedicine is an attractive and promising field that uses nanoparticles to serve as drug carriers. This field can improve the treatment of the complications of cardiovascular diseases including pulmonary arterial hypertension (PAH). PAH is an aggressive disease with a poor prognosis and low survival rates. Whilst there is no cure, there are several classes of vasodilator drugs that are used to treat PAH, including phosphodiesterase type 5 inhibitor (Sildenafil). Despite the great potential, these therapies are hindered by their systemic side effects. One way of overcoming this limitation is by encapsulating PAH drugs in a drug carrier using the nanotechnology appreoach. Currently, there are different types of clinically approved nanoparticles used to deliver drugs. In particular, the iron (Fe) containing nanoparticles from the metal organic framework MIL-89, are considered as promising candidates for drug delivery. In this study, we assessed the cellular uptake of Mil-89 and the cytotoxicity of Sildenafil-MIL-89 conjugate in PAH relevant cells as well as the loading capacity and release characteristics in vitro.
Methods: Confocal and light microscopy were used to assess the cellular uptake of MIL-89 by PAH relevant cells. MIL-89 was then loaded with Sildenafil and tested on the proliferation and viability of PAH relevant cells. In addition, the anti-inflammatory effect of sildenafil-MIL-89 conjugate on PAH relevant cells was monitored.
Results: Microscopic images showed the cellular uptake of MIL-89 at different concentrations by PAH relevant cells. Sildenafil-MIL-89 had no significant effect on the cell viability at a range of bioavailable concentrations. Moreover, the cytokine release (CXCl-8 and IL-1β) from PAH relevant cells was significantly reduced.
Conclusion: MIL-89 represents a safe and auspicious PAH drug carrier with good pharmacodynamics and anti-inflammatory properties.
Audience take away:
• This project aims to test the effectiveness of drug-delivery nanoparticles in the treatment of PAH, a devastating chronic disease with currently no effective cure. The outcomes of this study should guide therapy in the future and establish a novel nanotechnology-based drug delivery approach in the treatment of PAH. Eventually, such procedures once established could be transferable to benefit other diseases yet incurable such as cancer, neurological disorders, and cancer. Ultimately, this will likely add considerable value to current prevention programs and existing conventional therapies in patients with heart diseases.