Preparation of nanodelivery systems for oral administration of low molecular weight heparin

Abstract

Low molecular weight heparins (LMWHs) are only used parenterally. They have low oral absorption and bioavailability due to their high anionic charge density, exposure to enzymatic degradation and first-pass effect. The aim of this study was the development and evaluation of nanodelivery systems to increase the oral bioavailability of enoxaparin (low molecular weight heparin). In line with this goal, three nanosystems, such as three-layered nanofiber membrane (NF), enoxaparin loaded nanoparticles (NP) and three-layered nanofiber membrane loaded with enoxaparin nanoparticles (NP/NF) were prepared. As a result of the SEM images of nanofiber membranes, the surfaces of the fibers were found to be smooth and the fiber diameters were between 300 and 500 nm. Enoxaparin amount was found to be 390–400 μg/cm2 for nanofiber membranes. Porosity, specific surface area, contact angle, and work of mucoadhesion values were found to be 53.78%, 9.46 m2/g, 113.39°, 0.19 mJ/cm2 for NF formulation and 50.52%, 3.04 m2/g, 104.96°, 2.65 mJ/cm2 for NP/NF formulation, respectively. In vitro dissolution studies showed that less than 20% of the drug was released from the nanofibers at the end of 2 h in acidic pH. MTT studies showed that cell viability was more than 80%. Stability studies showed that there was no significant changes at three different storage conditions. In conclusion, nanodelivery systems were successfully prepared to increase the oral bioavailability of enoxaparin and to protect it from the acid pH of the stomach.