Title

Understanding the interactions between porphyrin-containing photosensitizers and polymer-coated nanoparticles in model biological environments

Document Type

Article

Publication Date

2016

Keywords

Gold nanostructure, Drug delivery, PEG coating, Controlled release

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 × 105 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.

Comments

Principal Investigator: Colin Heyes

Acknowledgements: This work was supported in part by the pilot project funds from the Arkansas Biosciences Institute, the National Institutes of Health (NIH P30 GM103450), the Ralph E. Powe Jr. Faculty Enhancement Award, and startup funds from the University of Arkansas, to J.C.; the financial support from Roswell Park Alliance to R.K.P.; and an appointment to S.V.J. to the Summer Student Research Program at the National Center for Toxicological Research administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. C.D.H. would like to thank the National Science Foundation (CHE-1255440) for financial support. K.Y.R. thanks the support from Student Undergraduate Research Fellowship (SURF).

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