(217p) Network Development and Modification From Water-Dispersible Nanogels

Nanogels are highly branched, internally crosslinked polymeric nanoparticles with overall dimensions on the submicron scale^[1].  Significant control over the chemical and physical composition, colloidal stability, and capacity for surface modification has made nanogels a popular candidate for biomedical applications, notably in the controlled release of therapeutic agents.  The internal network structure provides a tunable mechanism for both diffusion and degradation-mediated small molecule release.  Further manipulation of nanogel surface chemistry leads to more complex drug delivery platforms that include ligands for cell-specific targeting and pendant poly(ethylene glycol) for prolonged circulation time^[2],[3].  More recent studies have focused on integrating microgels and nanogels into composite polymer networks, providing great potential for controlling the content and distribution of network chemistry and modifying the final network properties.  Nanogel-containing hydrogels have been synthesized to provide a mechanism for controlled release within the gel.  Other studies have applied nanogels as pre-polymerized fillers to reinforce mechanical properties and provide thermal or pH-responsive functionality in soft materials and to mitigate polymerization shrinkage in glassy dental composites^[4],[5],[6]. 

We are particularly interested in using nanogels for manipulating the chemical and physical properties of water-based polymer networks.  Forming networks in aqueous conditions avoids the use of volatile, toxic organics and can be essential for biomaterials applications.  Our approach involves synthesizing polymerizable nanogels that serve as the primary basis for network construction.  Nanogels are obtained from the free radical solution polymerization of mono- and di(meth)acrylate monomers in an appropriate solvent with sufficient quantity of chain transfer agent to prevent macrogelation.  This method produces nanogels with molecular weights on the order of 100 kDa and diameters well below 100 nm.  Up to 30 mol% di(meth)acrylate was included in the monomer feed, which is a significantly higher crosslinker ratio than previously reported.  A resultant high chain-end density allows for facile introduction of functional groups including polymerizable units.  Initial demonstrations combined monomers of varying polarity that ordinarily phase separate in aqueous media, such as urethane dimethacrylate and poly(ethylene glycol) methacrylate, to form nanogels that provide stable, transparent pre-gel dispersions in water beyond 75 wt%.  Nanogels were photopolymerized to yield monolithic networks with minimal extractables.  Specific manipulation of intermolecular hydrogen bonding, particularly acid-urethane and acrylonitrile dipole interactions, resulted in a significant enhancement of mechanical properties and adhesive strength.  A wide range of properties were achieved, with rubbery modulus in the range of 20 kPa to 4 MPa and glass transition temperatures ranging from -20 C to 35 C.

Introduction of various surface-grafted chemistry was explored in addition to tuning bulk nanogel properties.  Michael addition of ene-functionalized nanogels with thiol-containing moieties is an efficient route for grafting secondary functionality.  Addition of thiolated peptides and subsequent copolymerization with PEG macromers results in nanoclustered functionality within hydrogels and was investigated for modulating cell response in hydrogel scaffolds.  The preparation of clickable nanogels can be achieved through the addition of norbornene groups which react rapidly with thiolated surfaces without bulk polymerization, which is a useful feature for forming conformal UV-initiated coatings.  This produces a method for combining drug release coatings with shape memory polymers, for instance, in which diffusion from the bulk polymer is restricted and degradation would compromise the primary shape memory function of the device.     Preparation of nanogels of diverse chemical content results in a versatile platform for designing polymer networks with unique and tunable properties. 

1) Graham, N.B.; Cameron, A. Pure Appl Chem.  1998, 70, 1271.

2) Raemdonck, K.; Demeester, J.; De Smedt, S. Soft Matter.  2009, 5, 707.

3) Chacko, R.T.; Ventura, J.; Zhuang J.; Thayumanavan, S. Advanced Drug Delivery Reviews.  2012, 64, 836.

4) Bencherif, S.A.; Siegwart, D.J.; Srinivasan, A.; Horkay, F.; Hollinger, J. O.; Washburn, N.R.; Matyjaszewski, K.  Biomaterials.  2009, 30, 5270.

5) Meid, J.; Dierkes, F.; Cui, J.; Messing, R.; Crosby, A.J.; Schmidt, A.; Richtering, W.  Soft Matter. 2012, 8, 4254.

6) Moraes, R.R.; Garcia, J.W.; Wilson, N.D.; Lewis, S.H.; Barros, M.D.; Yang, B.; Pfeifer, C.S.; Stansbury, J.W. Journal of Dental Research.  2012, 91, 179.

Grant support: NIH R01DE022348