(314d) 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