454276 Porous Organic Cages for Drug Delivery

Thursday, November 17, 2016: 1:06 PM
Golden Gate 4 (Hilton San Francisco Union Square)
Sophie Miller1, Shan Jiang2, Andrew I. Cooper2 and David Fairen-Jimenez1, (1)Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, United Kingdom, (2)Department of Chemistry, University of Liverpool, Liverpool, United Kingdom

Porous materials have shown significant promise in drug delivery applications due to their high surface areas for adsorption, tunable pore size and chemistry, and regular, well-defined porosity. While several inorganic or hybrid organic-inorganic porous materials have been studied as drug carriers, concerns exist regarding the potential toxic effects of metals present in these systems. Porous organic cages are individual organic molecules with intrinsic porosity that, under specific conditions, self-assemble window-to-window with close packing to yield all-organic crystals with continuous, interconnected channels. In this work, we present the first-ever evaluation of these porous organic cages, specifically CC3 and CC5, for their drug delivery properties and biocompatibility. Crystalline particles of CC3 and CC5 have been loaded with cancer therapeutics (dichloroacetate and α-cyano-4-hydroxycinnamic acid), caffeine (useful for medicinal and cosmetic applications), and calcein (a model fluorescent molecule), with loadings of up to 25% by mass achieved, as determined by thermogravimetric analysis. Drug release from loaded CC3 and CC5 over several days was tested under simulated biological conditions in phosphate buffered saline (PBS), and drug release curves were obtained via UV-vis spectrometry to determine the kinetics and efficiency of drug delivery. The materials have also been shown to be stable in both water and PBS for at least one week, with no loss in crystallinity observed in powder x-ray diffraction patterns. Finally, two cytotoxicity assays have been conducted using HeLa cells to determine the effect of these materials both on cell membrane permeability and on metabolic activity. Neither CC3 nor CC5 compromised cell membrane integrity up to a concentration of 3 mg/mL, and while no reduction in metabolic activity was observed after incubation with CC3, the effects of particle size and potential breakdown products of CC5 on cytotoxicity are being investigated.

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See more of this Session: Biomaterials for Drug Delivery II
See more of this Group/Topical: Materials Engineering and Sciences Division