Abstract:
Introduction: Myocardial infarction (MI) resulting from ischemic reperfusion injury (IRI) can be mitigated by pre/postconditioning. We therefore developed bioconjugated lipid polymer hybrid nanoparticles (LPHN) to target the CD44 biomarker at the site of IRI and deliver drug to reduce the MI size. Various drugs selected for MI treatment were encapsulated in LPHN and were administered to rats undergoing IRI to determine its efficacy. Materials and Methods: LPHN were synthesized by nanoprecipitation of PLGA in lecithin-DSPE-PEG solution. 59 rats underwent transient coronary artery occlusion for 35 mins. Vehicle (n=14), Myristic acid (n=11), Acacetin (n=11), low-dose (n=6) and high-dose (n=6) Dexamethasone (Dex) were administered 30 mins after reperfusion. CD44 and troponin I were measured 6h and 24h from reperfusion and histological % infarct s ize was measured 7d from MI. Plasma metabolomics was performed at 7d. Results and Discussion: TEM and DLS measurements showed that synthesized nanoparticles ranged from 100 to 150 nm in diameter. Troponin I concentration was reduced at 6h and 24h, in rats receiving Acacetin (p=0.02), and low-dose Dex (p=0.07) but increased at 24h by high-dose Dex (p=0.96). size was reduced 27% by Acacetin (p=0.06), and 46% by low-dose Dex (p=0.02) but increased 36% by high-dose Dex (p=0.02) and was unchanged by Myristic acid. Conclusion: Low-dose Dex appears to have protective effect in IRI; however high-dose Dex was detrimental. Acacetin showed a trend towards a protective effect, though the study was underpowered to assure this result. Myristic acid had a neutral effect on IRI.
