The use of nucleic acids as a drug to treat diseases such as cancer, hepatitis, and HIV is an exciting area of research that has been challenged by sufficient delivery to the nucleus of the cell. In recent years, the focus of nucleic acid delivery has shifted away from using viruses as drug delivery vehicles towards the use of synthetic polymeric constructs due to inherent safety concerns of using viral vectors. We report the encapsulation of double-stranded calf thymus DNA (ctDNA) by two-component poly(methacrylic acid) (PMAA)/ poly(N-vinylpyrrolidone) (PVPON) multilayer hydrogel capsules. The ctDNA was encapsulated by co-precipitating the ctDNA within CaCO3 inorganic microparticles and then employing a layer-by-layer technique to alternately deposit layers of PMAA and PVPON on the CaCO3 cores. The ctDNA-loaded (PMAA/PVPON) hydrogel capsules were then obtained by crosslinking of PMAA layers by cystamine followed by dissolution of CaCO3 cores with ethylene diamine tetraacetic acid. DNA loading was visualized by confocal microscopy using fluorescein isothiocyanate (FITC)-labeled ctDNA within the interior cavity of (PMAA/PVPON) multilayer hydrogel capsules. We show that these capsules exhibit a dual responsiveness behavior by releasing ctDNA by treatment with either ultrasound to mechanically burst the capsules or GSH to enzymatically degrade the cross-links and that the ctDNA released from the capsules is still functional. In addition to the increased safety, these hydrogel capsules also offer the advantage of being highly tunable in regard to shape, size, and targeting ability which can be modified for specific applications of the capsules.

Encapsulation and release of dsDNA through dual-responsive, biodegradable hydrogel capsules

253rd National Meeting (2017)

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