RESUMEN
High-concentration and low-viscosity antibody formulations are necessary when administering these solutions subcutaneously (SC) due to limitations on injection volume. Here we show a method to decrease the viscosity of monoclonal antibody solution by protein-polyelectrolyte complex (PPC) with poly-l-glutamic acid (polyE). The viscosity of omalizumab solutions was 90 cP at the concentration of 150 mg/mL. In the presence of 20-50 mM polyE, the viscosity of PPC solution of 150 mg/mL omalizumab dramatically decreased below 10 cP due to the formation of crowded solution. The crowded state of PPC, named aggregated PPC (A-PPC), contained water droplets with a diameter of 10 µm or larger with low antibody concentrations. In the presence of 60 mM or more polyE, the omalizumab solution was transparent with the viscosity of 40 cP or less, named soluble PPC (S-PPC). More importantly, the solutions of both A-PPC and S-PPC were fully redissolved by the addition of phosphate saline buffer confirmed by secondary structure, the amount of aggregates, and binding activity to antigen.
Asunto(s)
Anticuerpos Monoclonales , Composición de Medicamentos , Polielectrolitos , Estructura Secundaria de Proteína , Soluciones , ViscosidadRESUMEN
A novel design of anticancer drug delivery system, based on an electrostatic binding of negatively charged liposomes and cationic metalloporphyrins under physiological conditions, is reported. A lack of cytotoxicity of the iron(III) porphyrin-loaded liposomes and an efficient generation of a toxic hydroxyl radical (OH*) from a superoxide anion radical (O2-*) through the iron(III)-catalyzed dismutation and the Fenton-like reaction allow for a targeted necrosis of tumor cells where the concentration of O2-* is locally increased as a result of the reduced activity of superoxide dismutase and catalase in these cells.