Adsorption/desorption of human serum albumin at the surface of poly(lactic acid) nanoparticles prepared by a solvent evaporation process.

Biocompatible and biodegradable nanoparticles of poly(lactic acid) (100% L-lactic units = PLA) were prepared by an emulsion, microfluidization, and solvent evaporation method using human serum albumin (HSA) as a surface agent. A radiolabeling technique was employed to quantify the serum albumin bound to the nanoparticles and to measure its desorption kinetics in various media at 22 degrees C and 37 degrees C (phosphate buffer pH 7.4, serum albumin 40 g/L in phosphate buffer pH 7.4 and fetal calf serum). The amount of serum albumin bound to the nanoparticles was found to be a linear function of 1/D (where D is the nanoparticle mean diameter) and was related to the total developed area of the nanoparticles. The adsorption/desorption behavior of serum albumin at the surface of the nanoparticles suggested a multilayer adsorption model. Moreover, a part of the serum albumin molecules was irreversibly bound regardless of the incubation conditions. Consequently, the classical Langmuirian theories of equilibria could not be applied.

Body distribution of fully biodegradable [14C]-poly(lactic acid) nanoparticles coated with albumin after parenteral administration to rats.

Fully biodegradable polylactic acid (PLA) nanoparticles (90-250 nm) coated with human serum albumin (HSA) were prepared by high-pressure emulsification and solvent evaporation, using the protein as surfactant. A new analytical tool was developed, based on Mie's law and size exclusion chromatography, to establish that, after evaporation of the solvent, the protein saturates the surface of the nanoparticles, masking the PLA core. According to this technique, no HSA is encapsulated in the polymer matrix. A radiolabelled [14C]-PLA50 was synthesized to follow the fate of this new drug carrier after i.v. administration to rats. The time necessary to clear the albumin-coated nanoparticles from the plasma was significantly longer than for the uncoated ones but not extended enough to target cells other than mononuclear phagocytes. As deduced from whole-body autoradiography and quantitative distribution experiments, the 14C-labelled polymer is rapidly captured by liver, bone marrow, lymph nodes, spleen and peritoneal macrophages. Nanoparticle degradation was addressed following 14C excretion. The elimination of the 14C was quick on the first day (30% of the administered dose) but then slowed down. In fact, if the metabolism of the PLA proceeds to lactic acid which is rapidly converted into CO2 via the Krebs cycle (80% of the total excretion was fulfilled by the lungs), anabolism from the lactic acid may also have taken place leading to long-lasting radioactive remnants, by incorporation of 14C into endogenous compounds.