title: Cisplatin loaded methoxy poly (ethylene glycol)-block-Poly (L-glutamic acid-co-L-Phenylalanine) nanoparticles against human breast cancer cell.
abstract: Cisplatin (cis-diaminodichloroplatinum, CDDP) loaded methoxy poly (ethylene glycol)-block-poly (glutamic acid-co-phenyl alanine) [mPEG-b-P (Glu10 -co-Phe10 ) (PGlu10 ) and mPEG-b-P (Glu20 -co-Phe10 ) (PGlu20 )] nanoparticles with two different formulations (CDDP/PGlu10 and CDDP/PGlu20 ) are successfully developed in uniformly sizes. In 190 h, the CDDP/PGlu10 shows 30% release at physiological pH and 39% at lysosomal pH. Similarly, the CDDP/PGlu20 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/PGlu10 and CDDP/PGlu20 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/PGlu20 ) to 14 wt% (CDDP/PGlu10 ) left in 24 h. This prolonged blood circulation of CDDP loaded nanoparticles makes them as promising nanocarriers for tumor targeting delivery.
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, P. R. China; Department of Chemistry, Quaid-I-Azam University, Islamabad, 45320, Pakistan.
authors.forename: Zaheer
authors.initials: Z
authors.lastname: Ahmad
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Tang
authors.forename: Afzal
authors.initials: A
authors.lastname: Shah
authors.forename: Shixian
authors.initials: S
authors.lastname: Lv
authors.forename: Dawei
authors.initials: D
authors.lastname: Zhang
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xuesi
authors.initials: X
authors.lastname: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D005260:Female; D006801:Humans; D010455:Peptides / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D011099:Polyglutamic Acid / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D010455:Peptides; D011099:Polyglutamic Acid; C012001:polyphenylalanine; D011092:Polyethylene Glycols; D002945:Cisplatin
keywords: biocompatibility; cisplatin; controlled release; hemolysis; pharmacokinetics