Sustained release of heparin from PLLA micropartricles for tissue engineering applications

Abstract

Heparin holds promise for cardiac tissue engineering, but challenges such as hematoma or bleeding and accumulation in tissue caused by excessive release, and short half-life persist. The present study aimed to introduce a reliable mechanism for the prolonged heparin release from a biocompatible polymer carrier. The designed system must ensure that heparin retains its bioactivity over time while preventing premature release. Heparin was encapsulated within poly (L-lactic acid) microparticles using the double emulsion method, with polyvinyl alcohol employed as the stabilizer. The encapsulation efficiency of heparin in the microparticles was calculated as 25.56 %. The functionality of the design was evaluated using Attenuated Total Reflection Fourier Transform Infrared Spectroscopy, Scanning Electron Microscopy, and Energy Dispersive X-ray Spectroscopy. Drug release and microparticle degradation studies were conducted alongside cell viability tests. The particle sizes ranged from 5 to 10 ± 2.53 μm, with evidence suggesting that heparin promotes the smaller particle formation. The system demonstrated a consistent drug release profile over six weeks with a release rate of 54 % by week two and 97.65 % by week six. The degradation of heparin-loaded microparticles reached less than 50 % by week six, and the loading of heparin did not significantly affect the degradation behavior of the PLLA microparticles in PBS. Furthermore, heparin concentrations between 200 and 400 μg/ml enhanced the viability of Placenta-derived Mesenchymal Stem Cells and H9c2. These findings suggest that the system could be considered as an effective vehicle for sustained heparin delivery across a spectrum of biological applications, particularly in cardiac tissue engineering.

Keywords

• Heparin
• PLLA carrier
• Controlled release
• Microparticles
• Tissue engineering
• Cardiac tissue engineering