title: Polypeptide nanogels with hydrophobic moieties in the cross-linked ionic cores: synthesis, characterization and implications for anticancer drug delivery.
abstract: Polymer nanogels have gained considerable attention as a potential platform for drug delivery applications. Here we describe the design and synthesis of novel polypeptide-based nanogels with hydrophobic moieties in the cross-linked ionic cores. Diblock copolymer, poly(ethylene glycol)-b-poly(L-glutamic acid), hydrophobically modified with L-phenylalanine methyl ester moieties was used for controlled template synthesis of nanogels with small size (ca. 70 nm in diameter) and narrow particle size distribution. Steady-state and time-resolved fluorescence studies using coumarin C153 indicated the existence of hydrophobic domains in the ionic cores of the nanogels. Stable doxorubicin-loaded nanogels were prepared at high drug capacity (30 w/w%). We show that nanogels are enzymatically-degradable leading to accelerated drug release under simulated lysosomal acidic pH. Furthermore, we demonstrate that the nanogel-based formulation of doxorubicin is well tolerated and exhibit an improved antitumor activity compared to a free doxorubicin in an ovarian tumor xenograft mouse model. Our results signify the point to a potential of these biodegradable nanogels as attractive carriers for delivery of chemotherapeutics.
authors.affiliation: Department of Pharmaceutical Sciences and Center for Drug Delivery and Nanomedicine, College of Pharmacy, University of Nebraska Medical Center, 985830 Nebraska Medical Center , Omaha, NE , USA and.
authors.forename: Jong Oh
authors.initials: JO
authors.lastname: Kim
authors.forename: Hardeep S
authors.initials: HS
authors.lastname: Oberoi
authors.forename: Swapnil
authors.initials: S
authors.lastname: Desale
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Kabanov
authors.forename: Tatiana K
authors.initials: TK
authors.lastname: Bronich
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000494:pharmacology / Q000633:toxicity; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D003432:Cross-Linking Reagents / Q000737:chemistry; D004317:Doxorubicin / Q000008:administration & dosage* / Q000494:pharmacology / Q000633:toxicity; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D005260:Female; D005782:Gels; D006801:Humans; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D061986:MCF-7 Cells; D051379:Mice; D053758:Nanoparticles; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010316:Particle Size; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011099:Polyglutamic Acid / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D013997:Time Factors; D023041:Xenograft Model Antitumor Assays
chemical_list: D000903:Antibiotics, Antineoplastic; D003432:Cross-Linking Reagents; D004337:Drug Carriers; D005782:Gels; D011108:Polymers; C575477:poly(ethylene glycol)-block-poly(glutamic acid); D011099:Polyglutamic Acid; C034515:phenylalanine methyl ester; D011092:Polyethylene Glycols; D010649:Phenylalanine; D004317:Doxorubicin