title: The targeted delivery of doxorubicin with transferrin-conjugated block copolypeptide vesicles.
abstract: We previously investigated the intracellular trafficking properties of our novel poly(l-glutamate)60-b-poly(l-leucine)20 (E60L20) vesicles (EL vesicles) conjugated to transferrin (Tf). In this study, we expand upon our previous work by investigating the drug encapsulation, release, and efficacy properties of our novel EL vesicles for the first time. After polyethylene glycol (PEG) was conjugated to the vesicles for steric stability, doxorubicin (DOX) was successfully encapsulated in the vesicles using a modified pH-ammonium sulfate gradient method. Tf was subsequently conjugated to the vesicles to provide active targeting to cancer cells and a mode of internalization into the cells. These Tf-conjugated, DOX-loaded, PEGylated EL (Tf-DPEL) vesicles exhibited colloidal stability and were within the allowable size range for passive and active targeting. A mathematical model was then derived to predict drug release from the Tf-DPEL vesicles by considering diffusive and convective mass transfer of DOX. Our mathematical model reasonably predicted our experimentally measured release profile with no fitted parameters, suggesting that the model could be used in the future to manipulate drug carrier properties to alter drug release profiles. Finally, an in vitro cytotoxicity assay was used to demonstrate that the Tf-DPEL vesicles exhibited enhanced drug carrier efficacy in comparison to its non-targeted counterpart.
authors.affiliation: Department of Bioengineering, University of California, Los Angeles, 420 Westwood Plaza, 5121 Engineering V, Los Angeles, CA 90095, United States.
authors.forename: Brian S
authors.initials: BS
authors.lastname: Lee
authors.affiliation: Department of Bioengineering, University of California, Los Angeles, 420 Westwood Plaza, 5121 Engineering V, Los Angeles, CA 90095, United States.
authors.forename: Allison T
authors.initials: AT
authors.lastname: Yip
authors.affiliation: Department of Bioengineering, University of California, Los Angeles, 420 Westwood Plaza, 5121 Engineering V, Los Angeles, CA 90095, United States.
authors.forename: Alison V
authors.initials: AV
authors.lastname: Thach
authors.affiliation: Department of Bioengineering, University of California, Los Angeles, 420 Westwood Plaza, 5121 Engineering V, Los Angeles, CA 90095, United States.
authors.forename: April R
authors.initials: AR
authors.lastname: Rodriguez
authors.affiliation: Department of Bioengineering, University of California, Los Angeles, 420 Westwood Plaza, 5121 Engineering V, Los Angeles, CA 90095, United States.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Deming
authors.affiliation: Department of Bioengineering, University of California, Los Angeles, 420 Westwood Plaza, 5121 Engineering V, Los Angeles, CA 90095, United States. Electronic address: kamei@seas.ucla.edu.
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Kamei
mesh_terms: D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry; D016503:Drug Delivery Systems; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008962:Models, Theoretical; D010455:Peptides / Q000737:chemistry*; D011092:Polyethylene Glycols; D012995:Solubility; D014168:Transferrin / Q000737:chemistry*
chemical_list: D010455:Peptides; D014168:Transferrin; D011092:Polyethylene Glycols; D004317:Doxorubicin
keywords: 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide (PubChem CID: 15908); Ammonium sulfate (PubChem CID: 6097028); Block copolypeptide; Dimethyl sulfoxide (PubChem CID: 679); Doxorubicin; Drug delivery; Drug release; Mathematical modeling; N-hydroxysuccinimide (PubChem CID: 80170); Tetrahydrofuran (PubChem CID: 8028); Vesicle