Colloidal stability of polymeric nanoparticles in biological fluids

Abstract

Estimating the colloidal stability of polymeric nanoparticles (NPs) in biological environments is critical for designing optimal preparations and to clarify the fate of these devices after administration. To characterize and quantify the physical stability of nanodevices suitable for biomedical applications, spherical NPs composed of poly-lactic acid (PLA) and poly-methyl-methacrylate (PMMA), in the range 100-200 nm, were prepared. Their stability in salt solutions, biological fluids, serum and tissue homogenates was analyzed by dynamic light scattering (DLS). The PMMA NPs remained stable in all fluids, while PLA NPs aggregated in gastric juice and spleen homogenate. The proposed stability test is therefore useful to see in advance whether NPs might aggregate when administered in vivo. To assess colloidal stability ex vivo as well, spectrophotofluorimetric analysis was employed, giving comparable results to DLS.

Fig. 1

TEM of PLA NPs (a) and PMMA NPs (b)

Fig. 2

Effect of biological fluids on particle size—DLS measurements. PLA (a, c, e) and PMMA (b, d, f). Stock solutions: distilled water (filled diamond), PBS (filled square), isotonic (filled triangle), dextrose (filled circle); gastrointestinal fluids: synthetic intestinal fluid (shaded diamond), artificial lysosomal fluid (shaded square), saliva (shaded triangle), gastric juice (shaded circle); homogenates: serum (open diamond), brain (open square), spleen (open triangle), liver (open circle)

Fig. 3

Effect of biological fluids on NP stability—FI measurements. Stock solutions: distilled water (filled diamond), PBS (filled square), isotonic (filled triangle), dextrose (filled circle); gastrointestinal fluids: Synthetic intestinal fluid (shaded diamond), artificial lysosomal fluid (shaded square), saliva (shaded triangle), gastric juice (shaded circle); homogenates: serum (open diamond), brain (open square), spleen (open triangle), liver (open circle)