Microencapsulation of low molecular weight heparin into polymeric particles designed with biodegradable and nonbiodegradable polycationic polymers

Owing to its lack of oral absorption, heparin has to be administered parenterally. However, parental administration has negative aspects such as multiple injections, possible infection, patient inconvenience, and high cost. Now, low molecular weight heparin (LMWH) is taking part in antithrombotic treatment and is proven to confer more advantages than unfractionated heparin. The aim of our present study was to formulate, by the w/o/w emulsification process, LMWH microparticles as potential oral carriers prepared with biodegradable (poly-epsilon-caprolactone and poly-lactic-co-glycolic acid) and nonbiodegradable polycationic polymers (Eudragit RS and RL), used alone or blended. The encapsulation efficiency ranged from 16 to 47% and was highly dependent on the presence of the positively charged polymers. In the same way, a low in vitro LMWH release was observed when Eudragit polymers composed totally or partially the polymeric matrix, compared with biodegradable polymers exhibiting higher LMWH release (40 and 60%). For each formulation, LMWH released from microparticles preserved its biological activity as shown by the antifactor Xa activity. Experiments performed with fluorescein-labeled LMWH showed the drug distribution in microparticles and may give information about the mechanisms controlling LMWH encapsulation and release.