Development of amine-containing polymeric particles

The objective of this study was to synthesize and characterize particles as a drug-delivery platform for gliomas, a highly advanced and invasive stage of brain tumor with poor prognosis. Poly(aminoethyl methacrylate-co-methyl methacrylate) particles were prepared by suspension polymerization and poly(aminoethyl methacrylate-co-poly(ethylene glycol) methacrylate) particles were prepared by emulsion (w/o) polymerization. Amine groups of the particles were complexed with tetrachloroplatinate to form a cisplatin-like molecule. Particles were characterized with respect to size, zeta-potential, amine content, loading efficiency and drug release. Poly(aminoethyl methacrylate-co-methyl methacrylate) particles had diameters of below 10 mu m, whereas the poly(aminoethyl methacrylate-co-poly(ethylene glycol) methacrylate) particles had diameters of approx. 1 mu m. Poly(aminoethyl methacrylate-co-poly(ethylene glycol) rnethacrylate) particles had a more positive zeta-potential as compared to poly(aminoethyl methacrylate-co-methyl methacrylate) particles, although the amino-group content of both particles was almost equivalent. The net positive charge on the particles decreased after complexation with tetrachloroplatinate for both types of particles. Both particles had very high platinum-loading efficiency (>85%) and showed slow release of platinum over time. Particles had relatively low cytotoxicity (LC50 > 100 mu g/ml) and demonstrated a high degree of association with cells. Complexation with poly(aminoethyl methacrylate-co-methyl methacrylate) particles significantly reduced the toxicity of platinum. The poly(aminoethyl methacrylateco-poly (ethylene glycol) methacrylate) particles have potential for being an effective drug-delivery platform and continued investigation is warranted.