Monitoring the erosion of hydrolytically-degradable nanogels via multiangle light scattering coupled to asymmetrical flow field-flow fractionation.
We describe the synthesis and characterization of degradable nanogels that display bulk erosion under physiologic conditions (pH = 7.4, 37 degrees C). Erodible poly(N-isopropylmethacrylamide) nanogels were synthesized by copolymerization with N,O-(dimethacryloyl) hydroxylamine, a cross-linker previously used in the preparation of nontoxic and biodegradable bulk hydrogels. To monitor particle degradation, we employed multiangle light scattering and differential refractometry detection following asymmetrical flow field-flow fractionation. This approach allowed the detection of changes in nanogel molar mass and topology as a function of both temperature and pH. Particle erosion was evident from both an increase in nanogel swelling and a decrease in scattering intensity as a function of time. Following these analyses, the samples were recovered for subsequent characterization by direct particle tracking, which yields hydrodynamic size measurements and enables number density determination. Additionally, we confirmed the conservation of nanogel stimuli-responsivity through turbidity measurements. Thus, we have demonstrated the synthesis of degradable nanogels that erode under conditions and on time scales that are relevant for many drug delivery applications. The combined separation and light scattering detection method is demonstrated to be a versatile means to monitor erosion and should also find applicability in the characterization of other degradable particle constructs.
Smith
Michael H
MH
School of Chemistry and Biochemistry and Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia 30332, USA.
South
Antoinette B
AB
Gaulding
Jeffrey C
JC
Lyon
L Andrew
LA
D000178:Acrylamides / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D053758:Nanoparticles / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D012031:Refractometry / Q000379:methods*; D012542:Scattering, Radiation; D013696:Temperature
D000178:Acrylamides; D011108:Polymers; C045985:methacrylamide