INTERACTIONS OF POLY(LACTIC ACID) AND POLY(LACTIC ACID-CO-ETHYLENE OXIDE) NANOPARTICLES WITH THE PLASMA FACTORS OF THE COAGULATION SYSTEM

When surfactant-stabilized biodegradable poly(lactic acid) (PLA) parti cles are injected into rats, the rate of clearance from blood is fast. The rate can be strongly reduced by using particles made from diblock copolymers of PLA and poly(ethylene oxide) (PLA-PEO), resulting in an increased duration of contact with the components of the coagulation system. Thus, possible adverse effects such as activation of the coagu lation cascade could occur. In this paper, the interactions of surfact ant-stabilized PLA and PLA-PEO nanoparticle suspensions with the plasm a factors of the coagulation system are presented. PLA suspensions sta bilized by sodium cholate (PLA-Ch) interact with thrombin, factor V an d calcium ions. Formation of complexes and aggregates is induced by ad dition of calcium ions to PLA-Ch suspensions in the presence or in the absence of plasma. On the contrary; PLA-PEO suspensions are remarkabl y inert towards the coagulation factors and calcium ions, even when ch olate is present. Steric repulsion owing to the high surface density o f PEO is sufficient to avoid strong interations with the proteins and formation of aggregates between particles. (C) 1997 Elsevier Science L imited. All rights reserved.