Surface Hydrolysis Mediated Peg Conjugation of Poly(N-isopropyl acrylamide-co-acrylamide) Nanospheres

Surface Hydrolysis Mediated PEG Conjugation of

Poly(N-isopropyl acrylamide-co-acrylamide) Nanospheres

Jonathan Peters¹, Brandon Slaughter², Dr. Nicholas Peppas^1,2,3.

¹Department of Chemical Engineering, ²The Department of Biomedical Engineering, and ³Division of Pharmaceutics, The University of Texas at Austin, Austin, TX 78712

In order for thermally responsive poly(N-isopropyl acrylamide) (NIPAM)-based therapeutic nanocarriers to circulate in the blood stream for extended periods of time, they must typically be coated in a biologically inert polymer.  Poly(ethylene glycol) (PEG) surface tethers are often used for this purpose.   PEG coatings have demonstrated an ability to minimize protein binding, which prevents removal from the blood stream by the mononuclear phagocyte system.  Current methods for the passivation of PNIPAM-based particles require copolymerization with a PEG macromer (eg. Poly(ethylene glycol) monomethyl ether methacrylate).  The addition of these bulky PEG comonomers drastically alters the swelling response of PNIPAM-based hydrogels, rendering them ineffectual delivery vehicles. To eliminate the impact on swelling caused by PEGylation, a two-step method was developed to attach PEG tethers to the surface of P(NIPAM-co-acrylamide) nanospheres.  By maintaining NIPAM nanoparticles above their lower critical solution temperature (LCST), they de-swell, expelling water from the nanoparticle.  Thus, when the particles are exposed to basic conditions above their LCST, amide hydrolysis occurs only to surface-localized acrylamide monomers, where they are chemically-converted to acrylic acids.  This allows for attachment of amine functional PEG tethers by EDC-NHS chemistry.

Surface hydrolysis studies were conducted under controlled pH and temperature conditions, and characterized using potentiometric titration and zeta potential analysis.  Scanning electron microscopy, FTIR, NMR, and Zeta potential analysis were used to examine conjugation of PEG to the surface of the particles.  Swelling studies were conducted using dynamic light scattering (DLS) to study the effects of hydrolysis and PEG conjugation on swelling extent and triggering conditions.

Work supported in part by NIH grant    1 R21 EB012726-01