title: Formulation and photoirradiation parameters that influenced photoresponsive drug delivery using alkoxylphenacyl-based polycarbonates.
abstract: Recently, we reported the synthesis and biocompatibility of alkoxylphenacyl-based polycarbonates (APP); a promising new class of polymers that undergo photo-induced chain scission. In the current study, nanoparticles (NPs) were prepared from the APP polymer (APP-NPs) and loaded with doxorubicin (DOX) (DOX-APP-NPs) in order to identify and evaluate formulation and photoirradiation parameters that influence photoresponsive efficacy. Stable and spherical APP-NPs were prepared with diameters between 70-80nm depending on APP concentration (10-40mg/mL). There was a direct relationship between APP concentration and resultant particle size. Drug release studies indicated that exposure to the photo-trigger was capable of altering the rate and extent of DOX released. Photoresponsive DOX release was markedly influenced by the frequency of photoirradiation while the effect of APP concentration was most likely propagated through NP size. DOX released by photoactivation retained its efficacy as assessed by cytotoxicity studies in human lung adenocarcinoma (A549) cells. Studies in BALB/c mice indicated that DOX-APP-NPs induce less cardiotoxicity than DOX alone and that DOX-APP-NPs are not susceptible to dose dumping after photoirradiation.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Northeast Ohio Medical University, Rootstown, OH, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Wehrung
authors.affiliation: Department of Polymer Science, The University of Akron, Akron, OH, USA.
authors.forename: Elaheh A
authors.initials: EA
authors.lastname: Chamsaz
authors.affiliation: Department of Polymer Science, The University of Akron, Akron, OH, USA.
authors.forename: Abraham
authors.initials: A
authors.lastname: Joy
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Northeast Ohio Medical University, Rootstown, OH, USA. Electronic address: moyewumi@neomed.edu.
authors.forename: Moses O
authors.initials: MO
authors.lastname: Oyewumi
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems / Q000379:methods*; D006321:Heart / Q000187:drug effects; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D010775:Photic Stimulation / Q000379:methods*; D017319:Photosensitizing Agents / Q000138:chemical synthesis* / Q000528:radiation effects / Q000633:toxicity; D011076:Polycarboxylate Cement / Q000138:chemical synthesis* / Q000528:radiation effects / Q000633:toxicity
chemical_list: D017319:Photosensitizing Agents; D011076:Polycarboxylate Cement; C005506:polycarbonate
keywords: Biocompatibility; Cardiotoxicity; Doxorubicin; Nanotechnology; Photoresponsive; Polymer chain scission; Stimuli-responsive