title: Understanding the interactions between porphyrin-containing photosensitizers and polymer-coated nanoparticles in model biological environments.
abstract: Non-covalent incorporation of hydrophobic drugs into polymeric systems is a commonly-used strategy for drug delivery because non-covalent interactions minimize modification of the drug molecules whose efficacy is retained upon release. The behaviors of the drug-polymer delivery system in the biological environments it encounters will affect the efficacy of treatment. In this report, we have investigated the interaction between a hydrophobic drug and its encapsulating polymer in model biological environments using a photosensitizer encapsulated in a polymer-coated nanoparticle system. The photosensitizer, 3-(1'-hexyloxyethyl)-3-devinylpyropheophorbide-a (HPPH), was non-covalently incorporated to the poly(ethylene glycol) (PEG) layer coated on Au nanocages (AuNCs) to yield AuNC-HPPH complexes. The non-covalent binding was characterized by Scatchard analysis, fluorescence lifetime, and Raman experiments. The dissociation constant between PEG and HPPH was found to be ∼35 μM with a maximum loading of ∼2.5×10(5) HPPHs/AuNC. The release was studied in serum-mimetic environment and in vesicles that model human cell membranes. The rate of protein-mediated drug release decreased when using a negatively-charged or cross-linked terminus of the surface-modified PEG. Furthermore, the photothermal effect of AuNCs can initiate burst release, and thus allow control of the release kinetics, demonstrating on-demand drug release. This study provides insights regarding the actions and release kinetics of non-covalent drug delivery systems in biological environments.
authors.affiliation: Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, AR 72701, United States.
authors.forename: Samir V
authors.initials: SV
authors.lastname: Jenkins
authors.affiliation: Photodynamic Therapy Center, Roswell Park Cancer Institute, Buffalo, NY 14263, United States.
authors.forename: Avinash
authors.initials: A
authors.lastname: Srivatsan
authors.affiliation: Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, AR 72701, United States.
authors.forename: Kimberly Y
authors.initials: KY
authors.lastname: Reynolds
authors.affiliation: Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, AR 72701, United States.
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.affiliation: NCTR/ORA Nanotechnology Core Facility, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079, United States.
authors.forename: Yongbin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, AR 72701, United States.
authors.forename: Colin D
authors.initials: CD
authors.lastname: Heyes
authors.affiliation: Photodynamic Therapy Center, Roswell Park Cancer Institute, Buffalo, NY 14263, United States.
authors.forename: Ravindra K
authors.initials: RK
authors.lastname: Pandey
authors.affiliation: Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, AR 72701, United States. Electronic address: chenj@uark.edu.
authors.forename: Jingyi
authors.initials: J
authors.lastname: Chen
mesh_terms: D002462:Cell Membrane; D002734:Chlorophyll / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D016503:Drug Delivery Systems; D006046:Gold / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D053768:Metal Nanoparticles / Q000737:chemistry*; D008954:Models, Biological; D017319:Photosensitizing Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000737:chemistry / Q000378:metabolism*; D011166:Porphyrins / Q000737:chemistry / Q000378:metabolism*; D013499:Surface Properties
chemical_list: D017319:Photosensitizing Agents; D011166:Porphyrins; D002734:Chlorophyll; C083998:2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a; D011092:Polyethylene Glycols; D006046:Gold
keywords: Controlled release; Drug delivery; Gold nanostructure; PEG coating