title: Interaction of pHPMA-pLMA copolymers with human blood serum and its components.
abstract: Immediately after administration, polymer therapeutics are exposed to complex biological media like blood which may influence and alter their physicochemical properties due to interactions with proteins or serum components. Among such interactions those leading to larger sized aggregates can be sensitively detected by dynamic light scattering (DLS) as a pre in vivo screening method. Random copolymers from N-(2-hydroxypropyl)methacrylamide and lauryl methacrylate p(HPMA-co-LMA) and copolymers loaded with the model drug domperidone were characterized by DLS in isotonic salt solution and in blood serum. The bare amphiphilic copolymer micelles (Rh=30 nm in isotonic salt solution) formed large aggregates in serum of over 100 nm radius which were shown to originate from interactions with very low density lipoproteins (VLDLs). Encapsulation of the hydrophobic drug domperidone resulted, at first, in drug-copolymer formulations with larger hydrodynamic radii (39 nm<Rh<49 nm) which, however, did not induce aggregate formation in human serum. Since p(HPMA-co-LMA) copolymers were demonstrated to have a high potential for drug delivery into the brain, the knowledge of serum-copolymer interactions provides a better understanding of their function in the biological context.
authors.affiliation: Institute of Organic Chemistry, Johannes Gutenberg University Mainz , Duesbergweg 10-14, 55099 Mainz, Germany.
authors.forename: Mirjam
authors.initials: M
authors.lastname: Hemmelmann
authors.forename: Kristin
authors.initials: K
authors.lastname: Mohr
authors.forename: Karl
authors.initials: K
authors.lastname: Fischer
authors.forename: Rudolf
authors.initials: R
authors.lastname: Zentel
authors.forename: Manfred
authors.initials: M
authors.lastname: Schmidt
mesh_terms: D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood*; D008079:Lipoproteins, VLDL / Q000097:blood; D008823:Micelles; D011108:Polymers / Q000378:metabolism*
chemical_list: D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D008823:Micelles; D011108:Polymers