title: High-Capacity Drug Carriers from Common Polymer Amphiphiles.
abstract: We report herein a dual-purpose role for polyacidic domains in an aqueous-phase polymer amphiphile assembly. In addition to their typical role as ionized water-solubilizing and self-repulsive motifs, we find that polycarboxylic acid domains uniquely enable high levels of hydrophobic drug encapsulation. By attenuated total reflectance infrared spectroscopy, we find significant differences in the carbonyl stretching region of the nanoparticles formed by polyacidic amphiphiles relative to those in soluble, single-domain poly(acrylic acid), suggesting that stabilization may be derived from limited ionization of the carboxylate groups upon assembly. Acidic-hydrophobic diblock polyacrylates were prepared and coassembled with up to 60 wt % camptothecin (CPT) into nanoparticles, the highest loading reported to date. Controlled release of bioactive CPT from polymer nanoparticles is observed, as well as protection from human serum albumin-induced hydrolysis. Surface protection with PEG limits uptake of the CPT-loaded nanoparticles by MCF-7 breast cancer cells, as expected. Acidic-hydrophobic polymer amphiphiles thus have the hallmarks of a useful and general drug delivery platform and are readily accessible from living radical polymerization of cheap, commercially available monomers. We highlight here the potential utility of this common polymer design in high-capacity, controlled-release polymer nanoparticle systems.
authors.affiliation: Department of Chemistry and Biochemistry, The Ohio State University , 100 West 18th Avenue, Columbus, Ohio 43210, United States.
authors.forename: Zhun
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Department of Chemistry and Biochemistry, The Ohio State University , 100 West 18th Avenue, Columbus, Ohio 43210, United States.
authors.forename: Oliver
authors.initials: O
authors.lastname: Munyaradzi
authors.affiliation: Department of Chemistry and Biochemistry, The Ohio State University , 100 West 18th Avenue, Columbus, Ohio 43210, United States.
authors.forename: Xin
authors.initials: X
authors.lastname: Xia
authors.affiliation: Department of Chemistry and Biochemistry, The Ohio State University , 100 West 18th Avenue, Columbus, Ohio 43210, United States.
authors.forename: Da'Sean
authors.initials: D
authors.lastname: Green
authors.affiliation: Department of Chemistry and Biochemistry, The Ohio State University , 100 West 18th Avenue, Columbus, Ohio 43210, United States.
authors.forename: Dennis
authors.initials: D
authors.lastname: Bong
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002166:Camptothecin / Q000008:administration & dosage / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D006868:Hydrolysis; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D010316:Particle Size; D058105:Polymerization; D011108:Polymers / Q000008:administration & dosage* / Q000737:chemistry; D014407:Tumor Cells, Cultured
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D011108:Polymers; D002166:Camptothecin