Nano-particle engineered atorvastatin delivery to support mesenchymal stem cell survival in infarcted myocardium

Abstract

Atorvastatin (ATV) may support mesenchymal stem cells (MSC) survival in post-infarct myocardium (MI) as inflammatory reactions, oxidative stress and hypoxia condition get started in such tissues after damage. However, limited aqueous insolubility and rapid first-pass metabolism reduce the systemic availability of ATV. The aim of the present investigation was to develop ATV loaded nanoparticles (ATVNPs) which might ensure the maximum availability of ATV in systemic circulation for longer duration and to strengthen the support to MSC survival. ATVNPs were synthesized using double emulsion solvent evaporation method and characterized as spherical shape, positive charged, nanoparticles of uniform size distribution and higher entrapment efficiency. ATVNPs were non-cytotoxic and showed sustained release (up to 28 days). Assessment of cardiac function (in terms of echocardiographic and left heart catheterization parameters) and cytokines estimation revealed efficient improvement in post-infarct myocardium condition of rat. In conclusion, ATVNP was developed successfully that may ensure safe, cost effective, and efficacious treatment of post-infarct myo-cardium when compared with that of MSC alone and MSC supplemented with ATV solution.

Polymers and Nanoparticles for Statin Delivery: Current Use and Future Perspectives in Cardiovascular Disease

“…Strategies aimed at improving aqueous solubility [ 17 , 18 , 19 , 20 , 21 , 22 , 23 ], or prolonging the time on the gastrointestinal tract [ 24 , 25 , 26 ], were gradually replaced by approaches that use the lymphatic system for systemic absorption [ 16 , 27 ]. In fact, some nanoparticles were shown to be able to reach the lymphatic circulation of the intestine (M-cells and Peyer’s patches) [ 28 , 29 , 30 ], thus avoiding the enzymes of the enterocytes and the hepatic first-pass effect [ 16 , 31 ]. Cellulose-based polymers [ 16 ], were found to be superior [ 32 , 33 ], compared to cellulose-free polymers [ 27 , 28 , 29 , 30 ], because they guarantee a sustained release of the drug [ 32 ], due to better mucoadhesive [ 34 ], mechanical [ 35 ] and film-forming [ 35 ] properties and enhanced stability among physiologic pH levels [ 16 , 17 , 32 ].…”

“…In fact, some nanoparticles were shown to be able to reach the lymphatic circulation of the intestine (M-cells and Peyer’s patches) [ 28 , 29 , 30 ], thus avoiding the enzymes of the enterocytes and the hepatic first-pass effect [ 16 , 31 ]. Cellulose-based polymers [ 16 ], were found to be superior [ 32 , 33 ], compared to cellulose-free polymers [ 27 , 28 , 29 , 30 ], because they guarantee a sustained release of the drug [ 32 ], due to better mucoadhesive [ 34 ], mechanical [ 35 ] and film-forming [ 35 ] properties and enhanced stability among physiologic pH levels [ 16 , 17 , 32 ]. Among cellulose-free polymers, compounds with poly-oxy-propylene (hydrophobic fraction) and poly-oxy-ethylene (hydrophilic fraction) induced a 4-fold increase in the oral bioavailability of atorvastatin [ 17 ], but the intrinsic variability of the compounds in terms of dimension and composition should be carefully investigated in tailored studies.…”

Atorvastatin lipid nanocapsules and gold nanoparticles embedded in injectable thermo‐gelling hydrogel scaffold containing adipose tissue extracellular matrix for myocardial tissue regeneration

“…Numerous examinations have considered a particular portion of this medication powerful in the treatment of heart assaults, ventricular capacity alteration in myocardial damage, vascular dilatation, a decrease of fiery procedures in patients with heart failure, and lessening the rate of unexpected cardiovascular demise in patients with incessant heart failure. It has indicated the appropriate impact on vascular endothelial tissue and capillary walls in patients with ischaemic heart failure, and has a defensive impact in patients with myocardial localised necrosis [26][27][28][29][30].…”

Nanotechnology in cardiac stem cell therapy: cell modulation, imaging and gene delivery

“…But the efficiency of the molecule was largely reduced due to its limited systemic availability caused by its poor insolubility in aqueous environments. To address this limitation, Yao et al developed a nanoparticle-engineered ATV that ensured its maximum systemic availability, for a prolonged period and to support MSC survival in the injury site 68. Long back, Pons et al have reported the long-term culture of MSCs and showed the expression of cellular stress markers such as p16 INK , p21 and p19 ARF .…”