title: Aminoglycoside-derived amphiphilic nanoparticles for molecular delivery.
abstract: The development of effective drug carriers can lead to improved outcomes in a variety of disease conditions. Aminoglycosides have been used as antibacterial therapeutics, and are attractive as monomers for the development of polymeric materials in various applications. Here, we describe the development of novel aminoglycoside-derived amphiphilic nanoparticles for drug delivery, with an eye towards ablation of cancer cells. The aminoglycoside paromomycin was first cross-linked with resorcinol diglycidyl ether leading to the formation of a poly (amino ether), PAE. PAE molecules were further derivatized with methoxy-terminated poly(ethylene glycol) or mPEG resulting in the formation of mPEG-PAE polymer, which self-assembled to form nanoparticles. Formation of the mPEG-PAE amphiphile was characterized using (1)H NMR, (13)C NMR, gel permeation chromatography (GPC) and FTIR spectroscopy. Self-assembly of the polymer into nanoparticles was characterized using dynamic light scattering, zeta potential analyses, atomic force microscopy (AFM) and the pyrene fluorescence assay. mPEG-PAE nanoparticles were able to carry significant amounts of doxorubicin (DOX), presumably by means of hydrophobic interactions between the drug and the core. Cell-based studies indicated that mPEG-PAE nanoparticles, loaded with doxorubicin, were able to induce significant loss in viabilities of PC3 human prostate cancer, MDA-MB-231 human breast cancer, and MB49 murine bladder cancer cells; empty nanoparticles resulted in negligible losses of cell viability under the conditions investigated. Taken together, our results indicate that the mPEG-PAE nanoparticle platform is attractive for drug delivery in different applications, including cancer.
authors.affiliation: Chemical Engineering, The Biodesign Institute Arizona State University, Tempe, AZ 85287-6106, USA.
authors.forename: Bhavani
authors.initials: B
authors.lastname: Miryala
authors.affiliation: Chemical Engineering, The Biodesign Institute Arizona State University, Tempe, AZ 85287-6106, USA.
authors.forename: Sudhakar
authors.initials: S
authors.lastname: Godeshala
authors.affiliation: Harrington Biomedical Engineering, The Biodesign Institute Arizona State University, Tempe, AZ 85287-6106, USA.
authors.forename: Taraka Sai Pavan
authors.initials: TS
authors.lastname: Grandhi
authors.affiliation: Chemical Engineering, The Biodesign Institute Arizona State University, Tempe, AZ 85287-6106, USA.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Christensen
authors.affiliation: Center for Biosignatures Discovery Automation, The Biodesign Institute Arizona State University, Tempe, AZ 85287-6106, USA.
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Chemical Engineering, The Biodesign Institute Arizona State University, Tempe, AZ 85287-6106, USA. Electronic address: rege@asu.edu.
authors.forename: Kaushal
authors.initials: K
authors.lastname: Rege
mesh_terms: D000617:Aminoglycosides / Q000737:chemistry*; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D016503:Drug Delivery Systems; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008823:Micelles; D015394:Molecular Structure; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011108:Polymers / Q000737:chemistry; D014407:Tumor Cells, Cultured
chemical_list: D000617:Aminoglycosides; D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D008823:Micelles; D011108:Polymers; D004317:Doxorubicin
keywords: Doxorubicin; Drug delivery; Nanoparticles; Paromomycin