Cisplatin Loaded Methoxy Poly (ethylene glycol)-block-Poly (L-glutamic acid-co-L-Phenylalanine) Nanoparticles against Human Breast Cancer Cell

Cisplatin (cis-diaminodichloroplatinum, CDDP) loaded methoxy poly (ethylene glycol)-block-poly (glutamic acid-co-phenyl alanine) [mPEG-b-P (Glu(10)-co-Phe(10)) (PGlu(10)) and mPEG-b-P (Glu(20)-co-Phe(10)) (PGlu(20))] nanoparticles with two different formulations (CDDP/PGlu(10) and CDDP/PGlu(20)) are successfully developed in uniformly sizes. In 190 h, the CDDP/PGlu(10) shows 30% release at physiological pH and 39% at lysosomal pH. Similarly, the CDDP/PGlu(20) shows 60% release at physiological pH and 90% release at lysosomal pH. The sustained and controlled release of both formulations evidences the in vitro longevity of the nanoparticles. The cell proliferation inhibition of nanoparticles against human breast cancer cell line ZR-75-30 is dose and time dependent. Both CDDP/PGlu(10) and CDDP/PGlu(20) show excellent hemo compatibility as evaluated by hemolysis experiments. The in vivo fate of CDDP and CDDP loaded nanoparticles are evaluated by pharmacokinetics studies. Free CDDP underwgoes instant platinum concentration decrease after intravenous administration with 1.0 wt% left in 24 h while the CDDP loaded nanoparticles show prolonged blood circulation time with 5 wt% (CDDP/PGlu(20)) to 14 wt% (CDDP/PGlu(10)) left in 24 h. This prolonged blood circulation of CDDP loaded nanoparticles makes them as promising nanocarriers for tumor targeting delivery.