RELEASE OF THE FLUORESCENT MARKER PRODAN(R) FROM POLY(D,L-LACTIC ACID) NANOPARTICLES COATED WITH ALBUMIN OR POLYVINYL-ALCOHOL IN MODEL DIGESTIVE FLUIDS (USP-XXII)

Prodan(R) release from poly(D,L-lactic acid) (PLA(50)) nanoparticles c oated with albumin or polyvinyl alcohol (PVA) in simulated gastric and intestinal fluids (USP XXII) was investigated. Prodan(R) is a fluores cent marker, whose fluorescence properties enabled the concurrent dete rmination of the free and bound compound without prior separation of t he nanoparticles. In simulated gastric fluid, where the PLA(50) matrix of both PLA(50) nanoparticle systems coated with albumin or PVA was n ot degraded, the nanoparticles coated with albumin or PVA showed simil ar Prodan(R) release properties: Prodan(R) release from both nanoparti cles coated with either albumin or PVA was shown to follow kinetics co nsistent with diffusion through the intact polymeric matrix. One hundr ed percent release was obtained within 120 min. In simulated intestina l fluid, however, the Prodan(R) release from the PLA(50) nanoparticles was different depending on the agent coating the nanoparticles: when PVA was used as a coating agent, e.g. when no degradation of the PLA(5 0) matrix was observed, Prodan(R) was released by diffusion through th e intact PLA(50) matrix. Due to its very low affinity for water at thi s pH, only 44% of Prodan(R) was released. By contrast, Prodan(R) relea se from PLA(50) nanoparticles coated with albumin was driven by both m atrix erosion and diffusion processes. Accordingly, 100% release occur red over 480 min, despite the low affinity of Prodan(R) for the aqueou s phase at the pH of the simulated intestinal fluid.