Computational Study of DNA-Cross-Linked Hydrogel Formation for Drug Delivery Applications

We present the results of discontinuous molecular dynamics (DMD) simulations aimed at understanding the formation of DNA-mediated hydrogels and assessing their drug loading ability. Poly(ethylene glycol) (PEG) precursors of four and six arms that are covalently functionalized on all ends with oligonucleotides are cross-linked by a single oligonucleotide whose sequence is complementary to the oligonucleotide conjugated to the precursor. We show that the precursors with large molecular weight and many arms are advantageous in forming a three-dimensional percolated network. Analysis of the percolated networks shows that the pore diameter distribution becomes narrower as the precursor concentration, the number of arms, and the molecular weight increase. The pore throat diameter, the size of the largest molecule that can travel through the hydrogel networks without being trapped, is determined. The percolated network slows the movement of molecules inside the pores. Molecules larger than the pore throat diameter have more restrictions on their movement in the percolated network than those with smaller sizes.