ACRYLIC-ACID COPOLYMER NANOPARTICLES FOR DRUG-DELIVERY - STRUCTURAL CHARACTERIZATION OF NANOPARTICLES BY SMALL-ANGLE X-RAY-SCATTERING

Nanoparticles are possible carriers for drug delivery. Copolymer nanop articles of acrylic acid, acrylic amide, acrylic butylester, and metha crylic methylester (CAA) dispersed in water and in 0.15 M NaCl-solutio n were investigated by small-angle x-ray scattering (SAXS) experiments . The particles were characterized in terms of parameters relevant for the in vivo distribution: particle shape and diameter, size distribut ion, surface structure, and their organization within tight systems. T he CAA-nanoparticles exist in at least three populations of spheres wi th two minor subpopulations having radii of about 32 and 66 nm and the main moiety around 45 nm. The degree of polydispersity is R(w)/R(N) = 1.05. The subpopulations possess different hydrophobic areas on their surfaces, leading to different recognition by opsonins in vivo and di fferent organ distribution and clearance velocity. The particles are c ompact without channels and holes, which is proved by low internal hyd ration w = 0.22 g H2O/g polymer. Drugs and coating surfactants will in teract mainly with the outer surface and not tunnel into the carriers. The surface of the nanoparticles is fractal with a dimension D = 2.3. Probe-molecules with dimensions less than 11.4 nm in diameter will fi nd a larger contact area than expected from the sphere radius. Adsorpt ion rate and position of the arrival of surfactants, and possibly opso nins, may be affected thereby. The negative charges on the CAA-nanopar ticle surface are nearly completely screened in physiological NaCl-sol utions by counter-ions. Therefore, surface charges hamper carrier-cell interaction at short distances only and do not prevent specific recog nition and clearance by the reticuloendothelial system (RES).